1.Reminyl, A Novel Alzheimer's Treatment, Receives First EU Approval
(March 3,2000)

Beerse, Belgium/Andover, UK, 3 March 2000 - REMINYL(r) (galantamine), a new symptomatic treatment for dementia of the Alzheimer's type, received its first regulatory approval within the European Union from Sweden, announced Janssen-Cilag and Shire Pharmaceuticals Group plc (LSE: SHP.L, NASDAQ: SHPGY) today. Reminyl will subsequently be submitted through the EU Mutual Recognition Procedure to gain marketing approval in Europe.
Following successful approval, Reminyl will be registered and marketed by Shire in the United Kingdom and Ireland with a co-promotion agreement with Janssen-Cilag. Reminyl will be marketed in all remaining European countries by Janssen-Cilag. Reminyl is being developed by the Janssen Research Foundation and Shire under a co-development and licensing agreement.
Like other therapies currently on the market, Reminyl boosts the levels of acetylcholine in the brain by blocking the action of the enzyme acetylcholinesterase. However, unlike other therapies, research indicates that Reminyl has a second mechanism of action: it acts on nicotinic receptors in the brain. The "modulation" of these receptors is thought to increase the release of acetylcholine .1,2,3 An important feature of Alzheimer's disease is the progressive loss of cholinergic nerve cells, leading to a decline of critical chemical signals in the brain.
Submissions have also been made to the authorities in Canada, Australia, Switzerland, Poland, South Africa and New Zealand during the second quarter of 1999 and to the US Food and Drug Administration (FDA) at the end of September 1999. Janssen-Cilag will market Reminyl on successful approval in all these countries, except the US where Janssen Pharmaceutica will be responsible for marketing.
"Alzheimer's disease is a devastating illness for patients and their families. We are proud to introduce Reminyl as an important new treatment for this disease," said Jack Grebb, Senior Vice President, Janssen Research Foundation.
"This first approval for Reminyl in Alzheimer's disease leads the way forward for the UK and other European markets and represents good news for everyone involved in providing care for people with Alzheimer's disease," commented Dr. Wilson Totten, Shire's Group R&D Director.

2.Experts fear large increase in Alzheimer's as more people live longer
July 11, 2000

WASHINGTON (CNN) -- Researchers from around the world are focused their attention on detecting the early symptoms of Alzheimer's disease, at the second day of the World Alzheimer's Congress 2000 in Washington, D.C.
Their mission is given increased urgency by projections of the disorder's spread. More than 22 million people worldwide will be affected by Alzheimer's disease by 2025, researchers estimate. More than 12 million
suffer from it now.It is a primarily an affliction of aging; about 50 percent of Americans
over 85 have Alzheimer's.
Although there is no cure for Alzheimer's disease, scientists are learning more about what causes it, and identifying subtle symptoms of its onset.Plaques and tanglesDoctors have long known that Alzheimer's disease is related to key changes in the brain: the formation of so-called plaques and tangles. Plaques are protein deposits that eventually kill neural cells; tangles are accumulations of twisted protein fragments inside nerve cells.
What they don't know is how these two factors interact to cause Alzheimer's.
Researchers like Dr. Dennis Selkoe of Boston Brigham and Women's Hospital think the plaques are the primary cause. Selkoe believes the plaques -- called amyloid beta proteins -- may build up for 20 or 30 years and then
cause inflammation in the brain.The tangles, researchers think, probably develop later.
In addition to progressive memory loss and dementia, Alzheimer's disease can cause weight loss, incontinence, and difficulty moving. Many patients enter a vegetative state. From the onset of symptoms until death, the
average is 8 years but may range from 3 to 20 years, according to the Alzheimer's Association.
Mild cognitive impairment
But before having these symptoms, some people experience "mild cognitive impairment," which is "a slippery slope to Alzheimer's," neurologist Dr. Ronald Petersen of the Mayo Clinic told scientists at the Washington
conference.While everyone has occasional memory lapses, the memory loss from early-stage Alzheimer's is far more severe, affecting people's ability to work and causing problems with language or judgment.
People with mild cognitive impairment, also called MCI, fall between normal forgetfulness and early Alzheimer's.
"Their activities of daily living are performed fairly well," Petersen told CNN. "So they are out in the community living independently, driving, handling their checkbooks, doing their finances and doing pretty well."
Petersen is one of Ronald Reagan's physicians. The former president has Alzheimer's.
"In general, Petersen said, "when a person is diagnosed with having mild cognitive impairment, their risk of developing Alzheimer's disease is about 10 - to 15 percent per year." People without MCI typically develop
Alzheimer's at a rate of 1 percent per year.
Doctors use memory tests to help diagnose MCI, and blood tests can check for known genetic markers and a specific protein that may be an accurate predictor of Alzheimer's.
Also, magnetic resonance imaging -- or MRI, a procedure similar to an x-ray -- can scan the part of the brain called the hippocampus to detect changes in the structure of the brain associated with memory problems.
No cure, but targeted research Although no cure is available, "if we can characterize people clinically
early in the course of the disease such as mild cognitive impairment, we may be able to intervene," Petersen said.
Research is moving on two fronts, he said. One is designing drugs to have an impact on the progression of Alzheimer's. For example, studies are under way to determine if memory loss can be delayed by doses of Vitamin E, the federally approved drug called "Aracept," as well as estrogen and nonsteroid anti-inflammatory drugs.
"Researchers have identified the proteins that are involved in Alzheimer's disease that are deposited in the brain," he said. "They池e working on strategies now to prevent the deposit of that protein in the brain."
The other research push is to learn how to predict the disease before it develops and ultimately devise means to stop it.
Scientists have determined that certain genes make some families particularly vulnerable to Alzheimer痴. Head injuries may increase risk; high blood pressure is a new suspect.
But the biggest risk for Alzheimer's is age: Alzheimer's cases double with every five years of age between 65 and 85.
With global population aging, "we have an imminent worldwide epidemic," warned Edward Truschke, president of the Alzheimer's Association."We need to be able to at least delay the onset of Alzheimer's disease,"
said Dr. Robert Katzman of the University of California, San Diego, because even a treatment that fends off symptoms for a mere five years could halve the disease's burden.
CNN Correspondent Rhonda Rowland and The Associated Press contributed to this report.

3.Alzheimer's vaccine appears safe in human testing
Results presented at first World Congress on Alzheimer's
July 11, 2000

"By the end of the year we hope to make significant conclusions from those phase one studies, so that sometime in 2001 we can actually begin the key pivotal studies to see just how the vaccine's working."
The current safety trials are taking place in the United States and United Kingdom. When they're completed, the studies will expand to include several hundred patients at a number of medical institutions.
"Assuming everything works out, this vaccine not only will treat Alzheimer's Disease, but will also prevent Alzheimer's. It will completely change the face of Alzheimer's therapeutics now and forever if it works," said Dr. Ivan Lieberburg, executive vice president and chief science and medical officer for the Elan Corporation.
One year ago Elan researchers reported remarkable results of the vaccine in mice. Mice immunized at a young age were protected from Alzheimer's. In animals who already had the disease, the disease was halted and in some cases reversed.
"The amount of reduction of brain pathology was truly remarkable. It was as much as 99 percent reduced in animals that were treated with this vaccine," said Schenk.
Two other research teams have verified Elan's promising results in mice at the meeting. They've taken the work a step further, showing the vaccine produced improvements in behavior.
In addition, researchers and Brigham and Women's Hospital report encouraging results with a similar, nasal vaccine. "There is a 50-60 percent decrease in the amount of amyloid plaques and indeed the amount of a-beta proteins in the brains of mice who have gotten chronic nasal treatment," their report said.
Although it will take time to see if humans have the same results, other researchers say the safety trial results are encouraging.
"I think the vaccine immunization hypothesis is very exciting," said Dr. Ronald Peterson of the Mayo Clinic. "There is a lot of work that needs to be done with regards to its safety, its effectiveness, whether it will work in humans as it has in mice. But nevertheless, the major hypothesis is still very interesting for the possibility of prevention of the disease."
The vaccines are designed to attack the characteristic brain plaques of Alzheimer's. There is still some debate over whether the amyloid plaques are the cause of Alzheimer's dementia. The final outcome of the vaccine studies in humans should either prove or disprove the amyloid plaque theory as the cause of the disease.

4.Study: Head injuries early in life may lead to Alzheimer's disease
October 24, 2000

WASHINGTON (Reuters) -- Veterans who had serious head injuries decades ago now have a higher risk of Alzheimer's disease, a finding that suggests serious blows to the head may somehow cause delayed brain damage, researchers said Monday.
The more severe the head injury, the greater the risk of developing Alzheimer's, teams at the U.S. National Institute on Aging (NIA) and Duke University in North Carolina found.
The researchers said they do not know just what, biologically, is happening over the 50 years between injury and disease in the men, but said their study shows that Alzheimer's is a long-term, progressive condition.
"We found that head injury in early adult life was associated with increased risk of Alzheimer's disease and dementia in late life, and that this risk increased with the severity of the injury," the researchers wrote in their report, published in Tuesday's issue of the journal Neurology.
"Understanding how head injury and other Alzheimer's disease risk factors begin their destructive work early in life may ultimately lead to finding ways to interrupt the disease process early on," Brenda Plassman of Duke University, who helped lead the study, said.
The study does not show that injuries directly cause Alzheimer's, Dr. Richard Havlik of the NIA cautioned.
"While we may not fully understand what's going on, as a practical matter, it may be one more reason to wear that bike helmet instead of keeping it in a closet," he said. But then he added that the injuries the veterans suffered may have been very different from today's common head injuries, which often come during sports activities.
Havlik, Plassman and colleagues looked at the military medical records of male Navy and Marine World War II veterans who were hospitalized with a diagnosis of head injury or an unrelated condition. They used current Veteran's Affairs medical records to track down 548 veterans who had suffered a head injury and 1,228 veterans who had not.
They separated out those with mild injury, involving loss of consciousness or amnesia for less than 30 minutes with no skull fracture, moderate injury with loss of consciousness or amnesia for more than 30 minutes but less than 24 hours, or a skull fracture, and severe injury with loss of consciousness or amnesia for 24 or more hours.
The scientists then tested volunteers to see which of the veterans had Alzheimer's.
The risk of Alzheimer's and other forms of dementia was doubled in the men with moderate head injury, and it was four times greater in those who had severe head injury.
Havlik said inflammation could be involved.
"Clinical studies show that if somebody is in an acute accident and dies within a few days, there is a lot of damage to the brain," he said.
"There is evidence of amyloid, the building block of the famous plaques (that define Alzheimer's and which are found in the brains of Alzheimer's patients). Pathologists are seeing these within a few days or weeks of head injury."
Scientists believe the amyloid plaques are evidence of the brain trying to repair itself.
When brain cells are damaged, they send out many different chemical signals. For unknown reasons, some of these signals cause surrounding healthy brain cells to die.
Studies have also suggested that people who took anti-inflammatory drugs long-term, such as arthritis sufferers, have a lower risk of Alzheimer's.
Havlik said the study got around earlier problems of previous studies, which showed that people could not remember head injuries they got decades ago, or which were based on interviews with family members.
But he said other, unknown factors may have had a role to play. "We are talking about 50 years here," he said.

5.Isolation and strain: Families of Alzheimer's patients can be victims, too
September 25, 2000

NEW YORK (AP) -- Nancy Reagan, the former first lady, knows the despair of watching a loved one wracked by Alzheimer's disease. Lucy Chela Allen has felt it, too, nursing her ailing mother day after day in a modest apartment on the edge of Harlem.
As the number of U.S. Alzheimer's patients climbs past 4 million, the ranks of beleaguered care-giving relatives also swell -- millions of elderly spouses or grown children whose burdens make them highly vulnerable to emotional, physical and financial strain.
"I didn't have friends, I didn't feel I could cope," said Allen, 49, recalling difficult years juggling her care-giving chores and a middle-school teaching job. "I felt no one really understood what I went through -- what a hardship and sacrifice this was."
Many caregivers feel such isolation as they tend to the basic needs of loved ones whose memories and capacities have faded. Yet the Alzheimer's Association, devoted to raising national awareness of the disease, is heartened by signs that caregivers as a group are finally gaining recognition, even figuring in policy proposals of the presidential campaign.
"There is more conversation about caregivers and elder care than we've seen in a long time," said Judy Riggs, the association's director of state and federal policy.
"Bringing visibility is very important, so everyone realizes that long-term care is a costly proposition," she said in an interview. "It's not a problem we can solve cheaply."
Alzheimer's -- which affects one person in 10 over 65 -- already costs America an estimated $100 billion a year, and the price tag will soar as the elderly population increases. The Alzheimer's Association says 14 million Americans will have the disease by the middle of this century unless a cure or prevention is found.
The financial toll on relatives can be staggering, since neither Medicare nor most private health insurance covers the care that an Alzheimer's patient may need for 10 or more years. For patients staying at home, relatives either provide care themselves or pay an average of $12,500 per year for outside help. The cost for nursing home care averages more than $40,000 annually.
Beyond the expenses, caregivers face a higher-than-average risk of depression, stress and ill health. Elderly people strained by caring for an ailing spouse were 63 percent more likely to die within four years than other spouses, according to a University of Pittsburgh study.
Psychiatry professor Richard Schulz, who led the study, said many caregivers are unable or unwilling to take advantage of support programs offered in a growing number of communities.
"They feel they don't have time to go to a support group," he said.
Allen fit that description. From 1994, when she felt obliged to move back in to her mother's apartment, until last year, she devoted virtually all her free time to her mother's care because Medicaid funded only 36 hours of outside help per week. Last fall, she was able to obtain extra Medicaid coverage to get outside help 12 hours a day, seven days a week.
Her mother, now 87, sits quietly by a window, unable to carry on a conservation and seemingly not recognizing her daughter. Yet Allen is now able to see past the despair, and find satisfaction in repaying the love that her mother gave her over the decades.
"There's a major life lesson here," she said, "and I've learned so much."
At the Alzheimer's Association's New York City chapter, education and training coordinator Paulette Michaud presided over a recent meeting for family caregivers, urging them to join one of the city's many support groups. "People in support groups do better than those who don't join," she said.
Later in the evening, at a session with four caregiver families, she empathized when they complained about doctors who lacked expertise in coping with Alzheimer's.
"Doctors do feel impotent around this disease," Michaud said, urging the families to shop for a physician. "This illness is too long a process for you to suffer through medical advice that isn't useful to you."
Three sisters tearfully told Michaud how they struggle with guilt when they leave their ailing mother after visits to her nursing home.
"You are human beings -- you have limitations," Michaud consoled. "I don't want you beating yourselves over this."
Donna Zinczenko of Philadelphia said she regrets not having taken advantage of Alzheimer's Association support programs while trying to care for her mother before she was transferred to a nursing home.
Zinczenko, 47, said her mother refused to allow outside help into her home or travel to an adult day-dare center.
"It was a power struggle," Zinczenko said. "Even though she was in a depressed state, she held on tightly to this little bit of independence she had.
"I felt so overwhelmed with the minute-by-minute, day-by-day execution of her care that I didn't turn to the resources that were out there. I wish I had. The hardest thing is for people to accept the help that is out there."
New ways of helping are evolving constantly, such as teleconferencing and Internet connections to provide support for caregivers who feel they can't venture from home. Adult day-care centers and respite programs are proliferating.
Experts also are looking for ways to ease the physical toll on caregivers, who are particularly prone to neck and back problems as they lift or escort a patient.
Laura Gitlin, director of home-care research at Philadelphia's Thomas Jefferson University, oversaw a recent trial in which occupational therapists made a series of visits to caregivers to discuss ways of coping with specific problems.
The therapist might suggest how to simplify daily tasks to enable the patient to participate -- for example, arranging articles of clothing so they are easy to select and put on.
The therapist might suggest adjustments in the home to enhance safety or propose simple activities -- sorting of beads or coins -- to engage the patient's attention long enough to afford the caregiver occasional free time to rest or shower.
Sometimes the strain becomes unbearable. Last year, a New York State man committed suicide by running his car in a closed garage, and accidentally killed his mother as well when fumes infiltrated her bedroom. The woman suffered from Alzheimer's, and the son was struggling financially because he had quit his job to care for her.
Nancy Reagan, in a newly published book, voices the sentiments of many Alzheimer's caregivers as she describes the effect of the degenerative brain disease on her husband, Ronald Reagan.
"You know that it's a progressive disease and that there's no place to go but down, no light at the end of the tunnel," she writes. "You get tired and frustrated, because you have no control and you feel helpless."
The disease ravages families across the social and economic spectrum. But researchers say ethnic groups differ in the willingness to accept outside help.
"For a lot of Hispanic families, its extremely embarrassing, almost shameful, to admit there's a relative who has dementia -- it suggests there's something wrong with the bloodline," said Dolores Gallagher-Thompson, a psychologist at the Stanford University School of Medicine, who has worked with Hispanic families.
She said most of the families she worked with proved to be eager for assistance and advice once they overcame initial mistrust.
"We had to spend time shifting the emphasis from the patient to the family," she said. "We don't want the family to lose sight of the fact that they're important in this."
The two major presidential candidates also have promised not to lose sight of the role played by family caregivers. Vice President Al Gore has proposed a $3,000 per year tax credit to help compensate them, saying their sacrifices "are almost impossible to imagine." His Republican rival, George W. Bush, has proposed a 100 percent tax deduction for long-term care insurance premiums.
Judy Riggs of the Alzheimer's Association says none of the current proposals comes close to meeting the mounting costs. She suggests that long-term health care eventually will have to be covered by broad-based health insurance plans, the same way acute medical care is now.
"It's important that people pushing these proposals understand -- the problem won't go away," Riggs said.

6.New Alzheimer's drug(memantine) seems to slow disease progression, research shows
July 12, 2000

WASHINGTON (CNN) -- A new drug to treat Alzheimer's disease may help slow the progression of the disease in later-stage patients, according to a new study released Wednesday at the first ever World Alzheimer Congress.
The drug called memantine is the only drug tested to date for moderate to severe cases of the disease in later-stage patients. These are patients who are well enough to live at home under the supervision of a loved one, and who are perhaps a few steps away from going to a nursing home. These patients account for about one-third of all Alzheimer patients.
The six-month study conducted by Dr. Barry Reisberg, M.D. and Steve Ferris, Ph.D. at New York University School of Medicine included 250 volunteers from 30 U.S. centers. Half of the participants received the drug, the other half a placebo.
Researchers found that patients in both the placebo group and the treatment group continued to get worse. Those taking memantine, however, performed significantly better on cognitive tests and tasks of daily living such as dressing and bathing. Study results showed no difference in the level of aggression or agitation between the two treatment groups.
Researchers believe that memantine works on the area of the brain that has to do with thinking and memory.
The Food and Drug Administration has approved three drugs, Aricept, Exelon and Cognex, to treat mild to moderate Alzheimer's. There are no approved treatments for later-stage patients. Further testing of memantine is needed before the drug can be approved for widespread use in the United States.
Memantine is currently available in Germany to treat dementia assumed to be due to Alzheimer's. The drug is manufactured by Merz in Germany.

7.Hospital failed Alzheimer's patients
Monday, 24 January, 2000,(BBC.com)

A hospital trust failed to respond to reports that elderly, mentally-ill people were being abused in its care, says an official report.
Managers at Tolworth Hospital in Surbiton, south west London, were alerted to inadequate care provided for dementia and Alzheimer's Disease sufferers two years before an official inquiry began.
This has been a sad and shameful episode Ian Powe, inquiry chairman
In 1997, a senior nurse reported "potentially serious concerns" about the care of 25 patients in the hospital's Fuchsias Ward to the Kingston and District Community NHS Trust.
But the inquiry chairman, Ian Powe, said that the measures taken by the trust to control and assess the risk to patients were "totally inadequate".
A separate inquiry is being conduction into allegations of abuse at the hospital, which resulted in eight members of staff being suspended - although some were reinstated on appeal.
Relatives not given updates
Monday's report, however, said that there had been no attempt to provide "individual care" for patients, who had a "disagreeable routine" on Fuchsias Ward.
The inquiry found that most residents did not have their own clothes or toiletries, and were not encouraged to take part in activities.
Relatives and carers were not told when a patient's condition deteriorated, it added.
The situation was only seriously examined after two student nurses, who were shocked at what they saw on the ward, "blew the whistle", said Mr Powe.
Three months to improve
Levels of care on the Fuchsias Ward were "unacceptable" and staffing levels were inadequate, his report said.
But Mr Powe outlined that financial pressures on the health trust may have contributed to the ward's problems.
"Senior management apparently thought all was well on the ward but junior staff seemingly knew it was not," said the report, which recommended that the trust should introduce an immediate action plan.
Mr Powe said: "This has been a sad and shameful episode. Elderly, mentally-ill patients have been the silent victims of failure in corporate leadership, in management and in clinical care which have fallen fat short of standards people expect of their NHS.
"It's most important that there should be proper resourcing for the treatment of elderly people.
"We conclude form our study that the cost pressures in the health authority could be felt elsewhere in the country - and they must not be."
The panel has recommended the trust sets up an action plan within three months to improve conditions on Fuchsias ward.
A raft of recommendations urges them to employ at least five extra nurses for the ward and to make changes to working patterns, communication and extensively overhaul the management structure.

8.Cholesterol drug may prevent Alzheimer's
May 1, 2001 CNN.com

ATLANTA, Georgia (CNN) -- It's already known to dramatically reduce heart attacks and strokes. Now there's evidence that a commonly used cholesterol drug may also prevent Alzheimer's disease.
About 4 million Americans now suffer from Alzheimer's disease, and that number is expected to quadruple in coming years as the population ages. But scientists believe that statins -- better known by the brand names Lipitor, Zocor and Pravachol -- could help delay memory loss.
"What we found was that patients taking statins have a 60 to 70 percent reduction in the risk of Alzheimer's disease," said Dr. Benjamin Wolozin of Loyola University Medical Center in Illinois.
Scientists may have thought the surprising results a fluke, but a second study by a different research team came to the same conclusion.
"This is something that could be an important link, important future treatment for Alzheimer's," Wolozin said.
More studies under way
Researchers say the new findings make sense, since evidence has been accumulating from animal studies that cholesterol contributes to the build-up of amyloid plaques in the brain, a characteristic of Alzheimer's disease.
Although statins are considered safe and have few side effects, researchers say it would be premature to begin using them to prevent dementia or treat Alzheimer's.
The first study in the United States is under way to see if Lipitor is effective in treating the disease.
"We're attempting to slow the progression of the disease, based on the premise that there's this intimate link between cholesterol and the Alzheimer's toxin, beta amyloid," said scientist Larry Sparks of the Sun Health Research Institute in Arizona.
European researchers are studying the effects of Pravachol in almost 6,000 elderly people at risk for both cardiovascular disease and Alzheimer's.
"The aim in this study is to show that the use of Pravastatin to reduce their cholesterol levels will significantly reduce heart attacks, significantly reduce strokes and, most importantly, have an effect on the progression of cognitive decline," said Dr. Ian Ford of the University of Glasgow in Scotland.

9.Study: Dementia deadlier than first thought
April 11, 2001 CNN.com

(CNN) -- Nearly four million Americans suffer from Alzheimer's disease, a mind-robbing condition that can exact a terrible psychological and financial toll on victims and their families. But few people, including many physicians, consider the disease to be deadly.
But for older patients at least, an Alzheimer's diagnosis can be as devastating and potentially deadly as heart disease or cancer, according to a study published in the New England Journal of Medicine (NEJM).
The prevalence of Alzheimer's disease is projected to quadruple nationwide in the next 50 years, which means 1 in every 45 Americans will be afflicted with the degenerative condition, NEJM reported. The dramatic increase is primarily due to an aging population.
The effect an Alzheimer's diagnosis can have on families is enormous.
Gary Coleman has watched his mother, Esther, who is 86, struggle with Alzheimer's disease for about 10 years.
"It's never been presented to me as life-threatening or anything that would have to do with her life expectancy or her quality of life," Coleman said of his mother's diagnosis.
But The NEJM study found that patients 84 years of age and older will survive, on average, only three years after they first see a physician for symptoms that include memory loss.
That makes the disease as deadly as other major killers, according to Dr. Claudia Kawas of the University of California at Irvine, in an accompanying editorial.
"It's malignant and shortens the time you stay alive. Having said that," she added, "how much it shortens is determined by how old you are."
Most people don't think of dementia as a deadly condition, but "as time goes on they (patients) have difficulty swallowing, they may have difficulties walking," wrote Kawas, "and they become more susceptible to malnutrition and to infections."
"People with Alzheimer's disease, as time goes on, look very sick and they die just like people with cancer or heart disease or other chronic problems that are our leading killers," explained Kawas.
Life expectancy estimates, however, are just that -- estimates.
Atlanta-based geriatrician Dr. Jeff Lesesne advised caution when trying to predict how long a patient may survive after diagnosis.
"The course of events can be variable in the patient, and so it's hard to predict exactly what someone is going to experience," he said.
Alzheimer's disease attacks the nerve cells of the brain and impairs a person's memory, coordination and control over emotions. In its last stages, the disease robs its victims of all mental functioning.

10.Japan scientists find possible Alzheimer's cure
May 22, 2001(CNN.com)

TOKYO, Japan -- Japanese scientists say they have discovered a substance that offers the best hope yet of a cure for Alzheimer's disease.
Alzheimer's, which causes dementia in patients and is always fatal, is one of the most disturbing disorders among the elderly, with one million patients in Japan and another four million in the United States.
Ikuo Nishimoto, a professor of pharmacology and neurosciences at Keio University in Tokyo, said on Tuesday his team has discovered a protein, which they have named humanin, that can stop the death of brain cells that occurs in Alzheimer's patients.
But he also added that years of testing would be needed to determine whether humanin, produced naturally by genes in the rear part of the brain, can actually be used as a cure.
Stops brain cell death
"The difference between what we have discovered and what is currently used for treatment is that this completely stops the death of brain cells," Nishimoto told Reuters in an interview.
"This is the first step in completely curing Alzheimer's disease."
The discovery will be announced in a U.S. science academy bulletin, "Proceedings of the National Academy of Sciences of the United States of America," to be released later on Tuesday.
Nishimoto said his team, which has only conducted experiments in test tubes so far, will start testing the substance in animals, and added that Keio University was currently applying for a patent for humanin.
Alzheimer's disease has been in the spotlight recently, after U.S. federal prosecutors charged a Japanese scientist with stealing genetic material related to the disease and handing it over to a Japanese government-funded research institute.
More tests needed
Nishimoto said that further testing will be needed to determine whether humanin can actually cure Alzheimer's.
"Whether this can be used as a cure or not will depend on the results of testing," he said, adding this process could take as long as 15 years.
But Nishimoto said humanin has so far met all the conditions required as the cure for the disease.
"Humanin has so far met the various required conditions. For example, when you stop deaths of brain cells, it usually causes cancer. But humanin does not have such side effects," he said.
Japan has positioned itself as one of the leading nations in Alzheimer's research and many of its pharmaceutical companies have launched major marketing campaigns for medications aimed at slowing the early effects of the disease.

11.First gene therapy experiment for Alzheimer's
April 10, 2001

SAN DIEGO, California (CNN) -- In what is being called a medical first, doctors at the University of California, San Diego, announced Tuesday they performed gene therapy treatment surgery on an Alzheimer's patient.
The surgery was performed days ago on a patient with mild Alzheimer's disease. The therapy is not intended to be a cure, but it may protect or even restore brain cells and alleviate some symptoms such as short-term memory loss.
"Ideally we want to intervene as early as possible in this disease, before nerve cells degenerate," said Dr. Mark Tuszynski, the study's lead researcher at the University of California, San Diego.
The patient is a 60-year-old woman who is a former teacher from Oregon. She was diagnosed with Alzheimer's three years ago, and asked to remain anonymous.
Seven other patients will be involved in the initial study designed to assess the safety of the procedure. Researchers say if the gene therapy works, they may see memory or cognitive changes in the next several months.
"This is very interesting work since a lot of people have talked about doing gene therapy for Alzheimer's disease, but so far, no one's been able to work it out," said Bill Thies, Ph.D., with the Alzheimer's Association.
"However, we don't want to raise expectations that patients or family members will be able to get this treatment in the near future."
Skin cells taken from the patient were genetically engineered in the laboratory to produce and secrete human growth factor. In the surgical procedure, the genetically modified cells were implanted in the brain's frontal lobe, the area responsible for memory, thinking and reasoning. This area of the brain is referred to as the cholinergic system, which includes neurons that produce neurotransmitters, the chemical messengers used by the brain to process information. In Alzheimer's patients, the nerve cells in this system waste away and stop producing the neurotransmitters needed for normal functioning.
"In our study we need to answer two questions. First, whether preventing degeneration of this system is enough to improve cognition in Alzheimer's patients," said Tuszynski. "And second, will the nerve growth factor prevent death of cells from whatever is causing it."
Controversy remains over the exact cause of Alzheimer's disease. The leading theory is that the build-up of amyloid plaques in the brain begins the process of mental decline. The plaques consist of clusters of dead and dying nerve cells.
The rationale for beginning studies of this gene therapy in humans is based on 12 years of studies in rats and monkeys. Those studies showed the nerve growth factor gene therapy prevented the death of cholinergic cells and reversed aging cells.
"The functioning of these aging cells returned to normal," said Tuszynski. "We did see improvements in memory in old rats and young rats with brain injury."
The Alzheimer's Association said a major question to be answered is whether the implants will "take" in humans and remain "stable."
"It's possible the implants could start to divide and create a tumor setting," said Thies. "So there are certainly safety questions that will need to be answered."
A major challenge in treating Alzheimer's has been to find drugs that can cross the blood-brain barrier and reach the area of the brain that's affected by the disease.
"If this experiment works, it opens the possibility of delivering a number of drugs directly into the brain," said Thies. "The patient won't reject the genetically modified tissue since it's coming from the patient."
The UCSD researchers say they've selected the second patient who will undergo the procedure in the next three months. So far the team has received more than 500 inquiries from individuals interested in participating. To be eligible, patients must meet strict criteria including:
-- a neurologist-certified diagnosis of 'probably Alzheimer's disease'
-- early stage of the disease (generally within 2 years of diagnosis)
-- completely normal speaking ability and completely normal ability to understand what others are saying
-- ability to understand the potential risks of participation in the study
-- ability to travel to and from San Diego up to nine times in first year of study
-- willingness to discontinue use of FDA approved drugs Cognex or Aricept for the first 18 months of study.

12.Enzyme Breaks Down Alzheimer's Protein(neprilysin)
Thursday May 24(Yohoo news)
By Keith Mulvihill

NEW YORK (Reuters Health) - Japanese and American researchers reported on Thursday that a protein-dissolving enzyme in the brain may play a role in determining why some people develop Alzheimer's disease (news - web sites) and others do not.
The enzyme, known as neprilysin, appears to be responsible for breaking down amyloid-beta, the stubborn snippets of protein that form clumps in the brains of people with the memory-robbing illness. The findings, from a study of genetically engineered mice, are published in the May 25th issue of the journal Science.
The researchers hope that the finding may one day lead to a treatment for the devastating disease and perhaps an early detection test for people who may have a family history of Alzheimer's disease. The enzyme may be one of several responsible for breaking down amyloid beta in the brain.
``Amyloid is like garbage in the brain and neprilysin is a garbage disposer. If the garbage disposer is not working in the aged brain as well as it used to, the garbage piles up and starts to destroy the brain function,'' said lead researcher Dr. Takaomi Saido of the RIKEN Brain Science Institute in Wako-shi, in an interview with Reuters Health.
``We believe this is likely to cause the majority of late-onset Alzheimer's disease and our study is the very first to give experimental basis for this assumption, identifying neprilysin as the major garbage disposer. Once we know the cause, we will be able to fight the disease by removing the cause,'' he added.
In the study, Saido and colleagues looked at mice genetically engineered to lack neprilysin. They found that when these mice were injected with amyloid protein, they did not break down the protein. The amyloid-beta also tended to accumulate in the brain in areas that tend to form plaques in Alzheimer's patients.
The researchers believe that any drop in neprilysin activity--possibly due to aging--my be one of the key steps in development of the disease.
They hope that drugs or even dietary compounds will be found that elevate or inhibit neprilysin activity, explained Saido.
``Therefore, we may be able to avoid having Alzheimer's simply by taking the former and avoiding the latter. A more positive approach would be a gene therapy to introduce neprilysin gene in the brain,'' said Saido.
``These approaches may even help to prevent familial Alzheimer's caused by gene mutations,'' he added.
Although such plaques are found in Alzheimer's patients, it has not been clear if they are a cause or a result of the illness.
In a second study, published in the same issue of Science, Dr. Ron R. Kopito of Stanford University in California found evidence that the protein clumps do indeed result in cell death and dementia seen in Alzheimer's, Parkinson's and other diseases.
In their study of cells, Kopito's team found that protein accumulation directly impairs an important cell system, known as the ubiquitin-proteasome system. Cells use this to regulate important functions, such as cell division, and also to purge abnormally folded proteins from the cell. The protein clumps seem to set up a vicious cycle, whereas abnormal proteins clog up the system, leading to an accumulation of even more protein.
``This is pretty basic study of the cell biology of protein aggregation. It provides a plausible model of how intracellular protein aggregation could be toxic to cells,'' Kopito told Reuters Health.
Such protein build-up is a prominent feature of nearly all neurodegenerative diseases, and the findings suggest that a loss of protein elimination function could be one way in which protein aggregates could contribute to cell death, explained Kopito.
``Much more basic work needs to be done before this can lead to any obvious treatment directions,'' he added.
SOURCE: Science 2001;292:1550-1555.

13.Vaccine hope for Alzheimer's(UK)
June 6,2001(BBC.com)

The vaccine could prevent people developing Alzheimer's
A vaccine is being developed which it is hoped could prevent the onset of Alzheimer's Disease.
Tests are in their early stages, but scientists say that if trials on humans mirror the success of those on mice, the vaccine could "revolutionise" the treatment of the disease.
Eighty patients in four UK centres are taking part in the research.
Some experts have even suggested the treatment could reverse the progress of Alzheimer's, and that families could in future be screened for the disease, and those at risk immunised.
The pioneering treatment is described in 'Target Alzheimer's', a report from the Association of the British Pharmaceutical Industry (ABPI).
Some estimates suggest Alzheimer's costs the UK ｣5.5bn per year.
The ABPI say if the average age of the onset of the disease could be delayed by just five years, the number of people developing the disease - and the cost- could be halved.
Brain
Alzheimer's disease is linked to gradual formation of plaques made up of a particular protein in the brain.
These are called senile or amyloid plaques.
They are found close to nerve cells called neurons which are often swollen and distorted.
Scientists for the international pharmaceutical company Elan Pharma developed the vaccine, which is based on a toxic fragment of the main protein in the plaques.
The vaccine causes an immune response to the protein and seems to prevent the development of the plaques, and slow the deterioration of the nerve cells.
In tests, scientists used specially bred mice that carried a human gene, which meant they developed the plaques.
Some were given the vaccine and others were not.
Those who were given the vaccine retained the mental capacity to carry out tests such as finding their way around a maze, the report author Mike Hall told BBC News Online.
Those who were not vaccinated and developed the plaques were unable to successfully complete the memory tests.
Dr Hall said: "If you could vaccinate, you could find those people who are likely to get early onset Alzheimer's, and hopefully prevent them getting the disease in the first place."
The research into the treatment's effects on humans began around a year ago, but has only now reached therapeutic dose levels - the stage where the drug could have an effect on the disease.
Even if tests of the vaccine on humans are successful, it would be years before it was available.
Harry Cayton, chief executive of the Alzheimer's Society said: "If trials in humans prove to be effective we have the real hope of preventing at least one form of dementia but much research still needs to be done."
Harriet Millward, acting chief executive, of the Alzheimer's Research Trust, told BBC News Online: "Initial results from the Elan Corporation's anti-amyloid vaccine have given a huge boost to research into Alzheimer's disease.
"Not only do results indicate that the vaccine prevents the symptoms appearing, but that by breaking down the plaques, it may even reverse the effects of the disease.
"This is some of the most exciting research currently being undertaken into Alzheimer's disease.
"If all stages of the subsequent testing work, general availability of the vaccine could be four or five years away."
'Devastating condition'
Dr Trevor Jones, director general of the ABPI said: "Alzheimer's is a cruel and irreversible condition, not only for those who develop it, but for their family, friendly and carers.
"Medical science has made great strides in unravelling the mysteries of the brain and research into Alzheimer's has been particularly rapid.
"The development of new medicines is not only giving hope to those at risk from the disease but also offers the prospect of great financial savings for the country."
Alzheimer's disease is a progressive, degenerative and irreversible brain disorder that causes intellectual impairment, disorientation and eventually death.
It is one of a group of illnesses called dementia.
The Alzheimer's Society estimates dementia affects around 700,000 people in the UK

１４．Alzheimer's vaccine passes key test
July 23, 2001 Posted: 2:32 AM EDT (0632 GMT)

By CNN Medical Correspondent Rhonda Rowland

SAN FRANCISCO (CNN) -- An experimental vaccine designed to fight Alzheimer's disease appears to be safe in humans and is showing an immune response, according to scientists with Elan Pharmaceuticals.
The scientists report they have concluded the first phase of testing designed to assess safety, and will now take the vaccine into phase two clinical trials by the end of 2002.
Alzheimer's is a degenerative disease of the brain that inexorably attacks nerve cells, causing impairment and loss of memory and mental functions.
"We're extremely excited -- we're on the frontier of a completely novel approach to Alzheimer's disease," Dr. Ivan Lieberburg, executive vice president and chief scientific and medical officer of the Elan Corporation, told CNN.
The vaccine, called AN-1792, was studied in 100 patients with mild to moderate Alzheimer's disease in the United States and the United Kingdom.
"The product showed that is was safe for patients and we didn't see any significant problems with it other than sore arms at the injection site, which is what you would expect," Lieberburg said.
"More importantly, as well we saw that in a significant proportion of the patients they were able to demonstrate an immune response. Their antibody levels went up and that indicates that this was having an effect in these patients," he said.
The scientists did not indicate any cognitive or memory improvements in the patients but said they were reacting to the vaccine as mice did in previous experiments.
Official announcement of the trial results will be made by the company on Monday.

Remarkable results in mice
Lieberburg is hoping for a "truly remarkable result" from the vaccine
Elan is developing the vaccine with Wyeth-Ayerst Laboratories, the pharmaceutical division of American Home Products.
Two years ago, Elan researchers reported remarkable results of the vaccine in mice. Mice immunized at a young age were protected from Alzheimer's; in animals that already had the disease, the disease was halted and in some cases reversed.
"We're hoping that if we see anything like what we saw in our mice experiments in people in phase two clinical study, that this would be a truly remarkable result," Lieberburg said.
The Alzheimer's Association said Elan's announcement is an exciting development but should not preclude other avenues of research to find a way of preventing or curing the devastating disease.
"I think it's very exciting to see this product moving forward because it is going to be a test of one of the fundamental theories of Alzheimer's disease," said Dr. William Thies, vice president of medical and scientific affairs at the Alzheimer's Association. "While we don't know whether the product is going to work, we're going to find out an awful lot of valuable information no matter what the outcome of the trial is."

Vaccine attacks plaques
Thies says the testing is "very exciting" and will yield "an awful lot of valuable information"
The vaccine is designed to attack and clear out the characteristic beta amyloid plaques seen in the brains of Alzheimer's patients. There is still some debate over whether the amyloid plaques are the cause of Alzheimer's dementia.
"If it turns out that the vaccine clears the protein out and it still doesn't affect the disease, then that's a clear indication that amyloid is not the causative factor," said Thies.
If the vaccine does affect the disease process, it will not be able to cure the disease.
"For people who have well-established disease, the vaccine can do nothing to return dead brain cells and certainly can't return memories," said Thies, "although it could potentially arrest the disease in whatever stage the individual is in."
The next phase of testing will include 375 Alzheimer's patients at multiple centers in the United States and Europe

15.U.N. Report Cites Mental Problems

Story Filed: Thursday, October 04, 2001 1:20 PM EDT

GENEVA (AP) -- One in four people in the world will be affected by mental health or brain disorders during their lives, but few of them will seek or receive help, the World Health Organization said Thursday.
Some 450 million people suffer from mental and neurological conditions such as depression, schizophrenia and dementia. But despite this, about 40 percent of countries have no mental health policy, it said.
Two thirds of countries spent 1 percent or less of their health budget on mental health, and half had only one psychiatrist per 100,000 people.
``Mental Health: New Understanding, New Hope'' was the theme of the U.N. agency's annual health report.
The report also gave statistics showing the number of years spent in reasonably good health.
The Japanese had the highest healthy-life expectancy rates at 73.8 years, followed by Switzerland at 72.1 and San Marino at 72. Average healthy-life expectancy in the United States was 67.2 years.
Sierra Leone was at the bottom of the list with just 29.5 years of reasonable health.
``Mental illness is not a personal failure,'' said WHO Director-General Gro Harlem Brundtland. ``If there is a failure, it is to be found in the way we have responded to people with mental and brain disorders.''
With the proper treatment, people with mental illness can lead productive lives and be vital parts of their communities, the report said.
More than 80 percent of people with schizophrenia could be free of relapses at the end of one year of treatment with anti-psychotic drugs and adequate family support. Up to 60 percent of sufferers of depression could recover with the proper combination of antidepressants and therapy. Up to 70 percent of epileptics could be seizure free if treated with simple, inexpensive anti-convulsants, it said.
But even when help is available, nearly two thirds of people with a known mental disorder never seek professional help, often because of shame.
The report said one million people committed suicide every year, while 10 to 20 million attempted to kill themselves.
The poor were hardest hit.
``The lack of access to affordable treatment makes the course of the illness more severe and debilitating, leading to a vicious circle of poverty and mental health disorders that is rarely broken,'' WHO said.
The agency urged governments to draw up better policies on mental problems, including alcohol and drug abuse.
It said governments should shift away from large psychiatric hospitals, which are too restrictive and prone to human rights abuses, and introduce better community care programs.
More should be done to ensure availability of essential medicines, it said. About 25 percent of countries don't have the three most commonly prescribed drugs to treat schizophrenia, depression and epilepsy.
Copyright c 2001 Associated Press Information Services, all rights reserved.

The Honolulu Advertiser.com Saturday, October 13, 2001
16.Study looks at wanderings of Alzheimer's patients
By Curtis Lum, Advertiser Staff Writer

Dozens of Alzheimer's disease patients wander from their homes or caregivers each year, and a study explains that most of them do so because they are agitated or angry.
That's one of the conclusions of a year-long study by Meredeth Rowe of the College of Nursing and Institute of Aging at the University of Florida. Rowe analyzed data from the Alzheimer's Association's Safe Return program, which helps return individuals who wander from their caregivers.
Rowe reports that Alzheimer's patients are likely to wander when they are in unfamiliar situations and their caregivers become distracted. She also said that individuals are at greater risk of wandering if they are cared for by a son or daughter, rather than a spouse, because they are more likely to be left alone.
Hawai'i Alzheimer's advocates say the study is important because it will help them to advise caregivers on ways to prevent wandering.
"We're going to start targeting a lot more of the facilities to start talking about what you can do to reduce wandering," said Janet Bender, Alzheimer's Association Aloha Chapter executive director. "What are some environmental things you can do and maybe help them become more aware that there might be medical or physiological reasons."
Bender said caregivers don't always recognize causes of agitation.
"They could not be feeling well, and they're not able to express it. They could need to go to the bathroom, and they can't remember where to go. They could have agitation by thinking, 'I've got to take care of the children. I have to go do something.' They feel an urgent need to do something that they used to do from the past," she said.
Experts said that it is important that Alzheimer's patients not wander because nearly half of those who do may die if not found within 24 hours.
In Hawai'i, about 125 patients have been reported missing in the past 20 months and two have been found dead. At least seven have not been found, including Masayuki Kubo, 80, missing since June 23.
Bender urged family members and caregivers to register a patient with the association's Safe Return program. The program offers identification products, such as bracelets and pendants; a national database that includes photos; 24-hour toll-free crisis line; and wandering behavior education and training for caregivers and families.
Only about 700 of the state's estimated 19,700 Alzheimer's patients are registered.
There is a $40, one-time fee for the program, but it can be waived if a family cannot afford it.

Ecite News Updated: Mon, Nov 05 1:56 PM EST
17.Predictive Medicine Company, HealthScreen America, Launches Easy New Test That Helps Detect Alzheimer's Disease

JACKSONVILLE, Fla. (BW HealthWire) - A simple new urine test that helps detect Alzheimer's disease in the earliest stages -- when drug therapy may substantially delay the disease's devastating symptoms -- is now available directly to consumers at HealthScreen America.
Because of the effectiveness of this new test in identifying the Alzheimer's biomarker, it may serve as an alternative to invasive diagnostic procedures such as a lumbar puncture or spinal tap, said HealthScreen America's chief medical officer, Eduardo Balbona, M.D.
The Alzheimer's Association reports that 4 million Americans have Alzheimer's disease, with the number expected to increase by almost 50 percent in the next decade as the first baby boomers reach age 65. Alzheimer's is a disease of the brain that can go undetected for years as it causes permanent brain injury and interferes with everyday life.
"Experts agree that Alzheimer's requires identification in its earliest stages since this is when all currently available therapies are most effective at delaying the onset and progression of symptoms," said Balbona. Although there is currently no known cure for Alzheimer's, the FDA has approved several drugs that can slow the progression of the disease if prescribed early in the disease process.
The test is one example of an emerging field in medicine called Predictive Medicine, which specializes in detecting and halting disease at the earliest stages with 21st century revolutionary technology, Balbona said. HealthScreen America offers consumers direct access to more than 45 early disease detection tests including blood work, ultrasounds, CT scans and genetic tests.
The test costs $350 and requires a first morning urine sample and laboratory analysis. HealthScreen America will inform clients of his or her results within 7 to 10 days.
Blinded research studies demonstrated the test can be a powerful tool for physicians since it detects Alzheimer's disease 80 to 92.3 percent of the time (sensitivity) and can differentiate Alzheimer's from other diseases 90 - 97.1 percent of the time (specificity).
Physicians also gather other information, including a physical examination and neurological exam, to make a diagnosis. The only definitive test at this time is a brain biopsy performed during an autopsy.
There is still much unknown about Alzheimer's. Researchers believe Alzheimer's disease is caused when an abnormal protein called amyloid builds up in the brain, damaging nerves and killing brain cells. These changes eventually cause brain cell dysfunction, dementia and even death. In response to the brain injury, the nerves produce an increased level of another brain protein called Neural Thread Protein (NTP) as part of an attempt to repair the damage.
The Alzheimer's test at HealthScreen America measures NTP, which is increased even in early stages of the disease. An NTP measurement level greater than 18 units is considered a positive result and requires a physician's consultation.
"We are working closely with local physicians and organizations to ensure that clients with a positive result receive immediate assistance from those who are trained and prepared to offer expert advice and treatment," Balbona said. "While this can be distressing news, it is far better to discover the condition early while there is still time to affect the course of the disease. This is a quality of life issue and one that should not be ignored."
He added, "Early diagnosis also affords Alzheimer's patients time to talk to their family members and to be involved in planning for their own future including how their treatment and daily care will be managed as symptoms progress."
Balbona said the test would be helpful in ruling out or confirming Alzheimer's, but that it was not a substitute for the diagnostic protocols administered and evaluated by skilled physicians.
The test, called AlzheimAlert(TM), was developed by biopharmaceutical company Nymox Corporation (NASDAQ:NYMX).The Alzheimer's Association expects the number of individuals with Alzheimer's to more than triple in the next 30 to 40 years as baby boomers age, making widespread improvements in diagnosing and treating Alzheimer's imperative. While the disease can occur in people in their 30s, 40s and 50s, most are older than age 65.
HealthScreen America is a personal health management company offering consumers direct access to affordable, advanced medical technologies to screen for the leading causes of death and disability. Through its retail locations and mobile units, HealthScreen provides more than 45 low-cost, advanced screening tests for early detection of conditions including heart disease, stroke, osteoporosis, diabetes and cancers of the lung, colon, prostate and ovaries. The company also enables clients to store their DNA for future tests and screens for certain genetic diseases including hemochromatosis.
More information is available by calling toll-free 877-727-3366 or at http://www.HealthScreenAmerica.com.

18.Painkillers lower Alzheimer's protein in mice

By Amy Norton

NEW YORK, Nov 07 (Reuters Health) - Numerous studies have suggested over-the-counter painkillers may help fight Alzheimer's disease, but new research indicates that only certain ones can do the job and it may have nothing to do with their pain-relieving powers.
Various studies have hinted that nonsteroidal anti-inflammatory drugs (NSAIDs)--which include common painkillers like aspirin and ibuprofen--could help prevent or treat Alzheimer's disease. For example, some population studies have shown NSAID users to be at lower risk of developing Alzheimer's. And a recent study in mice suggested that ibuprofen could reduce the abnormal "plaques" that mark the brain in Alzheimer's.
Experts have speculated that this protective effect occurs, at least in part, because NSAIDs calm inflammation.
But in experiments with cells and genetically altered mice, US researchers have found that any Alzheimer's-related effects may be limited to certain NSAIDs and appear unrelated to the drugs' anti-inflammatory powers.
Instead, they report in the November 8th issue of Nature, ibuprofen and certain other NSAIDs may prevent the build-up of a particular Alzheimer's-linked protein called amyloid-beta 42.
This suggests that drugs designed to target this same process may fight Alzheimer's, while avoiding the dangers of giving high doses of NSAIDs, according to Edward H. Koo, Todd E. Golde and their colleagues.
"The surprising finding is that it is not going through an anti-inflammatory mechanism," Koo, a researcher at the University of California, San Diego, told Reuters Health.
Instead, he explained, this research suggests scientists should try to develop drugs that target amyloid-beta 42 the way some NSAIDs apparently do.
"This study does not endorse the use of NSAIDs for Alzheimer's," Koo emphasized, noting that such drugs can carry serious side effects such as gastrointestinal bleeding, particularly in the elderly.
Scientists have known that the brain plaques now considered a hallmark of Alzheimer's consist of amyloid-beta, a normally harmless protein. But Koo said no one has focused on the amyloid-beta 42 subtype as a drug target, despite the fact that some researchers believe this subtype may be key in the initial development of Alzheimer's disease.
In their research, Koo's team found that three NSAIDs--ibuprofen, indomethacin and sulindac sulphide--decreased amyloid-beta 42 in cell cultures, and ibuprofen did the same in mice.
However, other NSAIDs like aspirin, naproxen and celecoxib showed no such effects.
These findings could explain why some human studies have failed to find a benefit with certain anti-inflammatories, including the "best known NSAID"--aspirin, according to an editorial accompanying the report.
If the current findings "can be extended to people," certain NSAIDs could become the basis for new drugs to fight Alzheimer's, write Bart De Strooper of Flanders Interuniversitary Institute for Biotechnology in Leuven, Belgium, and Gerhard Konig of Bayer AG in Wuppertal, Germany.
However, since scientists already have a "wealth of clinical experience with NSAIDs," the editorialists also call for more studies of using these drugs among Alzheimer's patients.
SOURCE: Nature 2001;414:159-160, 212-216.

Volume 345:1515-1521 November 22, 2001 Number 21 (New England Journal of Medicine)

19.Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease

Bas A. in 't Veld, M.D., Ph.D., Annemieke Ruitenberg, M.D., Ph.D., Albert Hofman, M.D., Ph.D., Lenore J. Launer, Ph.D., Cornelia M. van Duijn, Ph.D., Theo Stijnen, Ph.D., Monique M.B. Breteler, M.D., Ph.D., and Bruno H.C. Stricker, M.B., Ph.D.

ABSTRACT
Background Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, have been inconsistent.
Methods We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine H2-receptor antagonists, antihypertensive agents, and hypoglycemic agents.
Results During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia.
Conclusions The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia.

20.Negative Effects of Caregiving for Spouse With Dementia May Last Years After Caregiving Ends, Study Finds
Story Filed: Wednesday, December 12, 2001 10:31 PM EST

COLUMBUS, Ohio, Dec 12, 2001 (ASCRIBE NEWS via COMTEX) -- The negative psychological impact of caregiving for a spouse with Alzheimer's or other forms of dementia continues for years after the spouse dies, new research suggests.
The study by researchers at the Houston VA Medical Center and Ohio State University found that, even three years after their spouse had died, former caregivers still showed levels of depression and loneliness similar to those in current caregivers.
For example, 41 percent of former caregivers showed mild to severe depression at two to three years after their spouses' death -- not significantly less than the 43 percent depression rate among current caregivers.
"One assumption has been that the psychological health of caregivers would improve once the burden of caregiving ends," said Susan Robinson-Whelen, the lead author of the study. "However, we found that the negative effects of long-term caregiving for a spouse with dementia may continue well beyond the caregiving years."
Robinson-Whelen began studying the health of caregivers as a post-doctoral fellow in psychiatry at Ohio State. She is now a researcher at the Center of Excellence on Healthy Aging with Disabilities at the Houston VA Medical Center. She co-authored the study with Yuri Tada, Robert MacCallum, Lynanne McGuire and Janice Kiecolt-Glaser, all of Ohio State. The study appears in the current issue of the Journal of Abnormal Psychology.
The researchers studied 49 former caregivers, 42 continuing caregivers and 52 noncaregiving control participants. The former and current caregivers all cared for a spouse suffering from some form of dementia, such as Alzheimer's disease. All the participants were assessed on a variety of psychological measures for four years. The former caregivers were tested once before the death of their spouse and three times following the death.
The most striking finding was that levels of depression did not significantly improve even two to three years after caregiving duties ended, said Kiecolt-Glaser, who is a professor of psychiatry at Ohio State. While many of the former caregivers showed evidence of relatively mild depression, it was still enough to impair their well-being, she said. Researchers were also concerned that the depression had not significantly decreased over time.
Kiecolt-Glaser noted that the control group in her study -- those who had never been caregivers -- had a depression rate of only 15 percent, compared to the rate of over 40 percent for former and current caregivers. "We didn't see the improvements you would hope and expect to see after caregiving has ended," she said.
Results also showed that former caregivers experienced fewer negative moods -- such as guilt and anger -- than did current caregivers, and did not differ significantly from noncaregivers in such negative mood states. However, former caregivers did not see a similar return to normal in how often they felt positive emotions, such as energy and enthusiasm. Even two to three years after caregiving ended, former caregivers reported fewer positive mood states than noncaregivers.
Moreover, former caregivers also showed higher levels of loneliness than did non-caregivers. "Most studies suggest many widowed people see improvements in their psychological health after a year or so of the death of their spouse," Robinson-Whelen said. "However, the former caregivers in this study still had relatively high levels of depression and loneliness even several years after the death of their spouse."
The former caregivers who were most likely to report psychological problems were those who said they often had recurring, unwanted thoughts about their caregiving experiences, or who said they tried to actively avoid such thoughts. Former caregivers who reported less social support from family and friends also were more likely to show signs of depression or other problems.
One area where former caregivers did show significant improvement was stress: after three years, former caregivers showed levels of stress very similar to those of non-caregivers. "You would expect that once the daily constant demands of caregiving were over that stress would go down," she said.
Robinson-Whelen said it is not known whether these results would apply to caregivers who cared for spouses with problems other than dementia. However, caring for a spouse with dementia may create special problems that make adjustment following death more difficult, she said.
However, the results do show that former caregivers may still need psychological help and support, even though their caregiving duties are over.
"Caregiving, especially for a spouse with dementia, is very difficult and the effects can linger for years," she said. "Former caregivers need more attention given to their needs."
The study was supported by grants from the National Institutes of Health and the Veteran's Affairs Rehabilitation Research and Development Service.
((AScribe - The Public Interest Newswire / http://www.ascribe.org))
(C)1999-2001 Ascribe News - http://www.ascribe.org
Copyright (c) 2001, AScribe Newswire, all rights reserved.

Public release date: 9-Jan-2002
Contact: Elaine Schmidt
elaines@support.ucla.edu
310-794-2272
University of California - Los Angeles

21.UCLA researchers invent first technique to image Alzheimer's onset

Findings will speed diagnosis, intervention and new therapies
UCLA scientists have created the first technique to image the earliest evidence of Alzheimer's disease in the living brain - before the disorder begins attacking brain cells. Reported in the January issue of the American Journal of Geriatric Psychiatry, the technique will allow doctors to monitor the disease as it unfolds - speeding diagnosis, intervention and new therapies for the disorder that afflicts 10 percent of people older than 65.
UCLA researchers combined a new chemical marker called FDDNP with positron emission tomography (PET) to see for the first time the brain lesions indicative of Alzheimer's disease in the living patient.
"We have developed the first tracer molecule that visually zeroes in on the brain lesions caused by Alzheimer's disease," said principal investigator Dr. Jorge R. Barrio, UCLA professor of medical and molecular pharmacology.
"This non-invasive method will help us monitor new vaccines and drugs designed to prevent and treat the brain damage caused by Alzheimer's disease," said co-author Dr. Gary Small, Parlow-Solomon Professor of Aging and UCLA professor of psychiatry and biobehavioral sciences.
Physicians regard these brain lesions, called amyloid plaques and tangles, as the definitive hallmarks of Alzheimer's disease. Experts suspect that the lesions' growth disrupts cell function and kills off brain cells, leading to disorientation and progressive memory loss.
Barrio and Small discovered that PET scans of patients injected with FDDNP showed the presence of early brain lesions - before the plaques are believed to destroy brain cells. If experts' hypotheses about the lesions' role prove accurate, UCLA's technique could identify when medical intervention may still stave off or prevent the onset of disease.
Using PET, the UCLA team detected high concentrations of FDDNP in the memory centers of nine Alzheimer's patients' brains. To verify their findings, the researchers performed a brain autopsy after one of the patients died. The post-mortem tissue showed FDDNP-stained lesions in the brain's memory centers - confirming the results of the patient's PET scan.
"When Alzheimer's disease strikes, the memory center is the first location where plaques take root and destroy brain cells," Barrio said. "So it's the first place where scientists must seek evidence of the disease."
Before UCLA's discovery, pathologists could make a definitive Alzheimer's diagnosis only by brain autopsy. As a result, physicians were able to treat Alzheimer's disease only after the disease has already caused apparent damage to the patient's memory. Furthermore, early clinical diagnostic methods produced accurate results 55 percent of the time.
"Most forms of dementia clinically look the same," Small said. "But if we can pinpoint the specific form of dementia, we can use the appropriate medication to postpone onset of the disease. This is a major gain."
"Combining the FDDNP marker with PET scans will enable us to better screen participants for clinical trials and produce more accurate research results," Barrio said. "This will bring new drugs to market faster with lower cost and improved accuracy for patients."
Pioneered by Dr. Michael Phelps, UCLA pharmacology chair, PET scans can differentiate Alzheimer's disease from the normal effects of aging. A drop in metabolism in one area of the brain indicates decreased activity in that region.
During the one-hour PET procedure, a technologist injects the FDDNP tracer molecule into the patient's arm after the patient enters the PET scanner. If lesions are present, the physician will see an accumulation of FDDNP in the brain's memory centers.
Barrio and Small's next step will be to refine the FDDNP-PET scan technique in order to monitor therapeutic drugs. The research team is comparing the PET scans of a larger group of Alzheimer's patients with those of unaffected individuals and patients with other dementias.
Alzheimer's disease afflicts nearly 10 percent of people older than 65. The condition often begins with mild memory lapses, then gradually advances to dementia - a progressive deterioration of memory, language and most mental functions. Alzheimer's patients eventually become bedridden and require constant care. The United States spends roughly $100 billion on the disease per year.
The UCLA study was supported by grants from the U.S. Department of Energy, Charles A. Dana Foundation, Alzheimer's Association, and the Institute for the Study of Aging Inc. Co-authors included Kooresh Shoghi-Jadid, Eric Agdeppa, Vladimir Kepe, Linda Ercoli, Prabha Siddarth, Stephen Read, Nagichettiar Satyamurthy, Andrej Petric and Sung-Cheng Huang.

Daily Yomiuri Online (January 11,2002)

22.Group finds Alzheimer's 'main cause'

In what could be a boost for victims of Alzheimer's disease, researchers at Osaka University have discovered a protein that kills cells in the cranial nerve of senile patients.
The university's Department of Medicine team, led by Prof. Masaya Toyama, believes the protein HMG-1 may be the main cause of senility, of which over 90 percent of Alzheimer's patients suffer from.
It has succeeded in synthesizing a "decoy" to lure the protein and will begin work on a new drug for senility with Taisho Pharmaceutical Co. to better current medicines that counteract only the symptoms and not the cause.
Further, studies show that the new process helps actually diagnose Alzheimer's, currently a major hurdle.
The researchers first dissected the brains of 17 victims of senility to detect the mutated form of a protein called presenlin 2 (PS2).
Although this protein causes hereditary Alzheimer's disease, which occurs at a comparatively young age due to abnormal genes, it is not believed to be responsible for senility in those who do not have abnormal genes.
The researchers, therefore, believed there was a problem with the PS2-making process from healthy genes and began research.
Normally, a protein is created with the help of an mRNA strand, which transcribes the data of a DNA and translates them onto the protein. The group discovered that the mRNA in senile Alzheimer patients is mutated.
The cause for the mutation is HMG-1, which is normally prevalent throughout the body. Its regular role is to attach itself to a DNA strand and regulate its function, but it is triggered to act abnormally by some as yet unknown cause.
The researchers then synthesized their "decoy" substance, which causes the HMG-1 protein to freeze all activities. They inserted the decoy into cells under similar conditions to those affected by Alzheimer's disease and saw that mRNA was produced normally and mutated PS2 proteins were not produced at all.
Furthermore, 1.5 to 2 times more mutated PS2 was discovered in the spinal fluids of patients afflicted with Alzheimer's compared to unaffected people.
Based on this, the group has also begun work on a medicine that examines the blood of Alzheimer's patients with a piece of equipment manufacturer in Kobe. If it can diagnose simple symptoms such as amnesia, it could eventually be able to cure and prevent the roots of the disease.

23.Stem cells offer hopes for improving memory loss
(Mainichi Shimbun, Jan. 13, 2002)
Alzheimer's disease sufferers' plight could be alleviated by stem cells, following an experiment by Japanese researchers.
Transplantation of stem cells extracted from a rat's germ into the brain of a rat with memory defects improved its problems, the experiment has proved.
The discovery could open the way for curing Alzheimer's disease that causes sufferers to become senile, researchers say.
In the experiment, the research team led by Keio University Prof. Hideyuki Okano and Kagawa Medical School Prof. Shogo Nagao injected a toxin into a rat's brain to prevent acetylcholine, a substance that transmits information from nerve cells to the brain, from being properly secreted, and thereby damaging its memory.
As a result, the rat became unable to walk to a destination that it had remembered. It also showed other symptoms of memory defects.
The researchers then extracted stem cells from a healthy rat's germ, developed them into nerve stem cells and transplanted them into the brain of the rat with memory defects. About a month later, the nerve stem cells restored the rat's ability to secrete acetylcholine and its memory returned to almost normal.
The discovery made in the experiment is likely to help in the development of a cure for Alzheimer's disease, the researchers said, noting that acetylcholine secretion disorders cause the illness.

24.Study: Drinking Can Ward Off Dementia
(By Emma Ross, AP Medical Writer January 24, 2002) Washingtonpost.com

LONDON -- A new study indicates that daily moderate consumption of alcohol, which has already been shown to help prevent heart disease and strokes, may also ward off Alzheimer's disease and other types of dementia.
The study, published this week in The Lancet medical journal, also found that it doesn't seem to matter what people drink - the effect is the same.
The finding adds to a growing body of evidence for the health benefits of moderate drinking.
Experts say moderation - between one and three drinks a day - is the key.
The adverse effect of excess alcohol is beyond question. Besides destroying the liver, several studies have shown that excessive drinking can be toxic to the brain. Alcoholics can end up with a shrunken brain, which is linked to dementia. There is even a medical condition called alcoholic dementia.
"For people who drink moderately, this is another indication that they are not doing any harm. And for those who don't, if they don't simply out of health concerns, they might want to rethink that position," said Meir Stampfer, professor of nutrition and epidemiology at Harvard School of Public Health, who was not involved in the study.
Scientists at Erasmus University in Rotterdam, the Netherlands, conducted a six-year study of 5,395 people aged 55 and over who did not have signs of dementia.
They were asked whether they ever drank alcohol. Those who said yes were quizzed on how often they drank and details on their consumption of specific drinks such as wine, beer, spirits and fortified wine such as sherry and port.
The men mostly drank beer and liquor, while women preferred wine and fortified wine.
The researchers also checked whether participants' drinking habits had changed over the preceding five years or whether they had engaged in binge drinking - more than six drinks in one day.
Everyone was categorized according to how much they drank. Four or more glasses of alcohol per day was considered heavy drinking.
By the end of the study in 1999, 197 of the participants had developed Alzheimer's or another form of dementia. Those who fared best were people who drank between one and three drinks a day. They had a 42 percent lower risk of developing dementia than the nondrinkers.
Those who weren't daily drinkers but had more than one drink per week had a 25 percent lower risk and those who drank less than a glass a week were 18 percent less likely than nondrinkers to develop dementia.
The number of heavy drinkers, who numbered 165 - mostly men - was insufficient to draw conclusions about any affect heavy drinking might have on dementia.
Recalculating all the figures for each type of alcohol separately, and comparing wine to other types of alcohol, yielded the same results.
"This red wine thing is a myth. The evidence for it is meager," said Stampfer. "It happens that red wine, in most cultures, is more likely to be consumed in moderation than spirits or beer, so for that reason it can appear to be specially protective, but in fact, the type of beverage does not matter."
Researchers suggested the blood-thinning and cholesterol-lowering properties of ethanol in alcohol may ward off dementia, which is often caused by a blood vessel problem.
Another possibility, the study speculated, is that low levels of alcohol could stimulate the release acetylcholine, a brain chemical believed to facilitate learning and memory.
On the Net:The Lancet, http://www.thelancet.com

25.Risky Alzheimer's surgery could hold promise
January 25, 2002
From Rhonda Rowland
CNN
SAN DIEGO, California -- Lola Crosswhite has never been one to shy away from a challenge. At 72, she's an avid photographer, fitness buff, scuba diver and downhill skier.
She's also a pioneering Alzheimer's patient -- only the third in the world to undergo an experimental gene-therapy procedure designed to slow the progression of the disease.
Surgeons at the University of California at San Diego (UCSD), have implanted genetically modified tissue deep in Crosswhite's brain. The tissue contains proteins called growth factors, which doctors hope will prevent the death of memory and reasoning cells, which typically degenerate in Alzheimer's patients.
"This won't be a cure," says Dr. Mark Tuszynski, the associate professor of neuroscience at UCSD who developed the procedure. "This will, if we are fortunate, slow the decline of the disease."
That would be enough for Crosswhite.
"If I could just stay where I am today and not get any worse, even that would be pretty wonderful because I am still able to enjoy my life, I am still able to do a lot of things," she says.
'I want this to be better'
Crosswhite has always been active. In her career days, she handled contract management and international sales for the aerospace industry, then started a business of her own with a partner. She also raised two children by herself.
But in her early 60s, Crosswhite began to notice that "something was not quite right." The diagnosis of Alzheimer's, when it came, was not a surprise, she says.
"Obviously, I didn't like that all that much, but I think to know is better than to wonder and wonder why you have such a hard time remembering things, and so to some extent to me it was a sense of relief."
The 11-hour procedure held substantial risks, but Crosswhite says she was willing to take them. She remained awake throughout the entire surgery.
"I don't really think about its being brave or not," she says. "It's just, to some extent, being selfish. I want this to be better."
Doctors had to insert long needles directly into Crosswhite's brain, which could have triggered bleeding. There was also the possibility that the added tissue could cause tumors, pain and even weight loss if not delivered to the right area. Being off-target by less than a quarter of an inch could render the therapy useless.
Adding to the complexity: Doctors had to give Crosswhite two MRI scans to make sure her brain had not been harmed.
"I think it's worth trying despite the risk," says Alzheimer's expert Dr. Leon Thal of UCSD, "because we stand to gain a tremendous amount of information about whether the approach will work. And then if it does, we're going to find simpler ways of trying to deliver the same type of compounds and get the same effect."
A month after the surgery, Crosswhite was back on the ski slopes.
And although it will be months yet before doctors will be able to tell if the gene therapy is slowing the progression of her Alzheimer's, Crosswhite says those who know her have noticed a difference already.
"People around me seem to feel that my short-term memory is much better than it used to be," she says. "That may be just wishful thinking, but I don't think so."

26.First-of-Its-Kind Study of Vascular Dementia Patients Taking ARICEPT(R) (donepezil hydrochloride tablets) Showed Significant Treatment Benefits Over Placebo in Cognition and Function
PR Newswire Date:January 25, 2002

- ARICEPT(R) Efficacy and Safety Study in New Treatment Area Presented
At The Second International Congress on Vascular Dementia (ICVD) -
SALZBURG, Austria, Jan. 25 /PRNewswire-FirstCall/ -- Treatment with ARICEPT(R) (donepezil hydrochloride tablets) significantly improved the cognitive and global (overall) function of patients with vascular dementia (VaD), compared with placebo, according to results from a first-of-its-kind clinical study presented today at the Second International Congress on Vascular Dementia (ICVD) in Salzburg, Austria. Only patients with VaD were included in this study. Patients with a diagnosis of Alzheimer's disease (AD) were excluded. ARICEPT(R) is currently indicated for the treatment of mild to moderate AD.
VaD, cognitive decline caused by a single, localized stroke, or series of strokes, is second only to AD as a cause of dementia. Up to one-third of all diagnosed dementia cases are VaD. In Europe, the prevalence of VaD is estimated to be 1.5 to 4.8 percent for people 70 to 80 years of age; of the patients over 65 years old diagnosed with dementia in the United States, approximately 9 to 39 percent have VaD.
This study is one of two conducted to examine the efficacy and safety of ARICEPT(R) in patients with VaD, excluding patients diagnosed with AD. The results of the second study are expected to be released in mid 2002. Eisai Co., Ltd., which discovered and developed ARICEPT(R), will work with its strategic alliance partner, Pfizer Inc., to file both studies with regulatory authorities worldwide for an indication to treat VaD.
"This groundbreaking study is the first time a cholinesterase inhibitor has been studied in a population composed primarily of patients with vascular dementia. VaD is a condition that has been underdiagnosed and undertreated," said Raymond D. Pratt, M.D., senior director, clinical research, Eisai Inc., who presented the data at the Second International Congress on Vascular Dementia (ICVD). "These results suggest ARICEPT(R) may be a promising option in treating VaD -- a condition for which there is currently no approved treatment."*
VaD is directly correlated with risk factors for stroke, including high blood pressure, diabetes, elevated cholesterol levels and smoking. The prevalence of VaD increases with age. Patients with VaD typically experience a stepwise decline in function, in contrast to patients with AD, who often experience a gradual, progressive decline. Like all forms of dementia, VaD results in significant physical, financial and emotional burden for patients and their families.
"Vascular dementia is an important and underrecognized problem," said Don Smith, MD, Colorado Neurological Institute and member of National Stroke Association's Prevention Advisory Board. "Clearly, the topic of vascular dementia deserves much more attention than it currently receives."
Study Details
The study included patients with VaD and excluded those with a diagnosis of AD. Patients were selected using research criteria specifically designed to identify patients with VaD. The criteria were developed by the National Institute of Neurological Disorders and Stroke (NINDS) with support from the Associate Internationale pour la Recherche et l'Enseignment en Neurosciences (AIREN).
The NINDS-AIREN criteria define VaD as cognitive decline involving memory loss, as well as impairment in at least two other cognitive domains that interfere with activities of daily life. These domains include orientation, attention, language-verbal skills, coordination, calculations, executive functions, motor control, functionality, abstraction, and judgment. Patients were also required to have neuroimaging evidence of cerebrovascular disease obtained by a computed tomography (CT) scan or magnetic resonance imaging (MRI).
This 24-week, double-blind, randomized, placebo-controlled study, included 616 men and women with VaD, with an average age of 75 years. The majority of participants had a history of stroke. Virtually all (99.7 percent) participants took one or more other medications, most frequently to prevent cardiovascular risk factors, with over 80 percent receiving some form of medication to prevent strokes.
Participants received daily doses of either 5 milligrams (mg) ARICEPT(R) (donepezil hydrochloride tablets), 10 mg ARICEPT(R) or placebo. Patients who received ARICEPT(R) showed significant improvement in their cognitive function compared to those taking placebo (P = 0.001, 5 mg; P <0.0001, 10 mg), as measured by the Alzheimer's Disease Assessment Scale (ADAS-cog), a standard test of cognitive abilities. Evaluation of global function also revealed significant improvements for patients at both ARICEPT(R) doses compared to patients who received placebo (P= 0.004 and P= 0.047, respectively), as measured by the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC-plus), a standard global assessment tool.
"Patients with VaD are often prescribed numerous medications to treat primary cardiovascular diseases such as blood pressure, cholesterol-lowering and diabetes drugs," said Sandra E. Black, M.D., Head, Division of Neurology, Sunnybrook & Women's College Health Sciences Centre, University of Toronto. "In this study, ARICEPT(R) was well-tolerated, even when taken with other medications."
Adverse Events
Overall, adverse events did not differ significantly in frequency between the ARICEPT(R) (donepezil hydrochloride tablets) groups (90.4 percent for 5 mg patients; 91.6 percent for 10 mg patients) and the placebo group (86.5 percent). Rates of cardiovascular events were also similar among all study participants (19 percent for 5 mg group; 20 percent for 10 mg group; 22 percent for placebo). As expected and consistent with the drug's known mechanism of action, side effects related to the digestive system, including diarrhea and nausea, occurred more frequently in ARICEPT(R)-treated patients than placebo-treated patients. Other adverse events that occurred significantly more often in ARICEPT(R)-treated patients were accidental injury, insomnia, leg cramps, rhinitis, and abnormal dreams. Overall, 491 patients (79.7 percent) completed the study and 125 (20.3 percent) discontinued, including 73 (11.9 percent) who discontinued due to an adverse event. No deaths were considered to be related to ARICEPT(R).
Information About ARICEPT(R) Treatment in Alzheimer's Disease
While there is no cure for Alzheimer's disease, medical treatments are available to manage symptoms of the disease. Once-a-day prescription ARICEPT(R), indicated for mild to moderate Alzheimer's disease, can improve cognition and maintain patient function.
In a progressively degenerative disease such as Alzheimer's, improvement, stabilization or a less-than-expected decline over time is considered a positive response to treatment. These types of responses have been observed in patients treated with ARICEPT(R) in clinical trials. Individual responses to treatment may vary.
ARICEPT(R) is well tolerated but may not be for everyone. Some people may experience nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, or loss of appetite. In studies, these side effects were usually mild and temporary. Some people taking ARICEPT(R) may experience fainting. People at risk for ulcers should tell their doctors because their condition may get worse.
ARICEPT(R) (donepezil hydrochloride tablets) is the number-one prescribed Alzheimer's medication worldwide with more than 450 million days of patient use; more than 1.7 million people in the United States alone have begun ARICEPT(R) therapy.
It is estimated that 1 in 10 individuals older than age 65 has Alzheimer's disease. Approximately 4 million Americans are thought to have the disease; by the year 2050, it is estimated that nearly 14 million Americans will suffer from Alzheimer's.
For more information about managing Alzheimer's disease and about ARICEPT(R), please call the toll-free number, (888) 999-9616, or see http://www.aricept.com.

27.New Alzheimer's Risk Factor Identified
High Homocysteine Levels Double Your Risk, but B-Vitamins May Help
By Salynn Boyles
WebMD Medical News

Feb. 13, 2002 -- High blood levels of a substance called homocysteine have been linked to an increased risk for both heart attack and stroke. Now, new research finds it to be a major risk factor for Alzheimer's disease and other age-related dementias.
If confirmed, the association between homocysteine and three of the major diseases of aging suggests the exciting possibility that these diseases might be prevented by simply taking your vitamins. It is known that B-vitamins like folic acid, B-6, and B-12 lower homocysteine levels. It is not clear, however, whether supplemental doses of these vitamins are protective against disease.
"The good news is that we may have found a potential risk factor for Alzheimer's disease that is modifiable," says Neil Buckholtz, PhD, who is chief of the Dementias of Aging program at the National Institute on Aging (NIA). "We don't know yet whether reducing homocysteine levels will reduce dementia risk, but this is something that can and will be tested in clinical trials."
In the latest homocysteine study, Boston University School of Medicine researchers found a strong link between elevated plasma levels of homocysteine and Alzheimer's risk in a group of 1,092 elderly people enrolled in the ongoing Framingham Heart Study. During eight years of follow up, 111 of the participants developed dementias, including 83 diagnosed with Alzheimer's disease.
Those with elevated blood homocysteine levels at entry into the study were twice as likely to develop Alzheimer's during the follow-up period as those with lower levels of the substance in their blood. The study, published Feb. 14 in The New England Journal of Medicine, is the first to link homocysteine levels in the years before symptoms develop with dementias associated with aging.
"We expected to find some effect, but we did not expect it to be so large," lead author Sudha Seshadri, MD, tells WebMD. "Homocysteine has emerged as a very important risk factor for [heart] disease. Our study suggests that it is also important in Alzheimer's. Now we have to find out if lowering homocysteine levels decreases risk."
The National Institute on Aging is planning a nationwide study to evaluate whether high supplemental doses of folic acid, B-6, and B-12 can slow the rate of mental decline in people with Alzheimer's disease.
And that strategy has already worked to decrease the number of birth defects that are linked to low blood levels of folic acid. In 1998, the Food and Drug Administration mandated that folic acid be added to grain foods like flour, rice, and cereals. Earlier findings from the Framingham Heart Study found that homocysteine levels fell about 7%, and folic acid levels doubled, following the change.
Although hopeful that such an action would successfully decrease the risk of dementia, scientists say that it's still too early to recommend vitamins for this purpose. "Scientifically, it is premature to say that people should take these vitamins in supplement form on the basis of our data and other studies," Seshadri says. "But this reinforces the importance of eating a healthy diet. The best way we know of decreasing homocysteine levels is eating lots of green leafy vegetables, fruits, and whole grains."
The findings point to chemical causes for age-associated dementias. Another major study released this week finds evidence that behavior is also key. When it comes to brain function, the research suggests, you have to use it or lose it.
An ongoing, nationwide study of elderly Catholic nuns, brothers, and priests found that those who routinely participated in brain-stimulating activities were at reduced risk for developing Alzheimer's. The more the participants performed activities like reading newspapers and books, the greater the protective effect. The study was published Feb. 13 in the Journal of the American Medical Association.
Those reporting frequent brain-stimulating activities at the beginning of the observation period were found to be 47% less likely to develop Alzheimer's disease over four and a half years of follow up than were those reporting infrequent cognitive activities.
Physical activity was not found to be associated with a reduction in risk. "This observation is important," the researchers wrote, "because it suggests that the association of cognitive activity with disease risk reflects mental stimulation rather than a nonspecific result of being active." The study was conducted by researchers at Chicago's Rush Institute for Healthy Aging.

28.Alzheimer victim selects embryo free of disease
By David Derbyshire, Science Correspondent
(Filed: 27/02/2002)
www.telegraph.co.uk

A WOMAN who knows that she will develop Alzheimer's within 10 years has used a controversial embryo screening technique to "select" a baby free from the disease that has blighted her family.
Unlike her mother, aunt and uncle, the baby girl does not carry a rare genetic mutation that triggers the onset of dementia before the age of 40.
Doctors who carried out the process said the technique could be used to screen embryos for other genetic conditions that strike later in life, such as breast cancer or Huntington's disease.
But critics warned that the advance took medicine a step closer to an era of "designer babies" and questioned whether it was appropriate to "weed out" embryos for diseases that do not develop until middle age.
There are also concerns that the mother will be unable to care for her child when she develops Alzheimer's.
Details of the procedure were reported yesterday by a team led by Dr Yury Verlinsky, a leading fertility expert and director of the Reproductive Genetics Institute, Chicago.
The mother was a 30-year-old American who carried a gene mutation, known as V717L and found in around a dozen families worldwide. It almost always causes Alzheimer's disease in the mid to late 30s.
The woman's sister developed dementia at 38. Her brother also showed symptoms in his 30s. A baby born to a carrier of the gene has a 50:50 chance of inheriting the disease.
The team used preimplantation genetic diagnosis (PGD) to screen 15 embryos created with in vitro fertilisation. PGD is carried out on a single cell removed from an embryo three days after conception when it has six to 10 cells.
Four of the embryos free from the mutation were implanted into the woman. One developed into a healthy baby girl.
The researchers, who published details of the test in the Journal of the American Medical Association, said it was the first known successful PGD for early-onset Alzheimer's.
Although the particular gene mutation carried by the mother is extremely rare, a more common single gene mutation is responsible for an estimated 3,000 to 4,000 cases of early-onset Alzheimer's in Britain.
Last night Dr Verlinsky told The Telegraph that the procedure could be used for that gene, and for families with a history of breast cancer, colon cancer or Huntington's disease.
He said he was happy to use the technique on "predisposition genes" - those that increase the risks of an illness, rather than guarantee it.
"If there is a late onset disease in the family, then I believe that they are entitled to screening," he said. "The other option is to screen during pregnancy and terminate, which I think would be worse."
The report comes just days after the Human Fertilisation and Embryology Authority ruled that a British couple could create a test tube baby to help save the life of their three-year-old son who suffers from a rare blood disorder.
The couple will use IVF to create several embryos and PGD will be carried out to select a baby with the same tissue type. Stem cells from the baby's umbilical cord will then be transplanted into the little boy to "repair" his bone marrow.
Under HFEA rules for IVF treatment, doctors can screen embryos for "serious genetic conditions". It is up to the HFEA on a case by case basis to decide whether a particular disease is "serious".
Harry Cayton, chief executive of the Alzheimer's Society, said of the American case: "This raises serious ethical concerns because this is an illness that people develop later in life.
"It is a different decision to the one parents might make if they knew a child was going to be born with cystic fibrosis and so would suffer and be ill all their life. Who knows what might happen to someone before they reach their late 30s."
The rogue gene interferes with the production of the protein amyloid, triggering the build up of "plaques" in the brain. The plaques kill brain cells and eventually the sufferer.
Prof Jack Scarisbrick, the chairman of the anti-abortion group Life, said: "The whole thing smacks of a kind of attitude to human life that easily degenerates into consumerism. We only want the best products and so we send back those that are not right."

29.Blood Test for Alzheimer's New Test Predicts Telltale Plaques in Brains of Live Mice
By Liza Jane Maltin
WebMD Medical News

March 21, 2002 -- The only way to accurately diagnose Alzheimer's is to examine the patient's brain after death, but researchers have come up with a blood test to identify Alzheimer-type changes in living mice.
Developed in part by WebMD sponsor Eli Lilly and Co., the new test predicts the amount of telltale plaque in the brain.
"We don't know if this finding in mice will apply to humans," says study leader David M. Holtzman, MD, in a news release. "If it does, it has the potential to provide a non-invasive means of detecting Alzheimer's pathology even before clinical symptoms appear." Holtzman is the Charlotte and Paul Hagemann Associate Professor of Neurology and associate professor of molecular biology and pharmacology at Washington University School of Medicine in St. Louis.
The findings appear in the March 22 issue of Science.
Recently, scientists have discovered that physical changes can begin in the brains of Alzheimer's patients 10-20 years before they ever show symptoms. For unknown reasons, these people experience a build-up of dangerous amounts of a particular protein that eventually clumps together in the brain to form plaques.
The brain plaques of Alzheimer's disease are akin to the plaques that clog arteries, leading to heart attack. The researchers want to develop a blood test that can predict Alzheimer's disease before symptoms begin, just like an angiogram of the blood vessels can predict an impending heart attack, says researcher Steven M. Paul, MD, group vice present at Lilly Research Laboratories.
The team looked at 49 mice with a genetic predisposition to Alzheimer's disease. The researchers evaluated these animals' blood for plaque-forming proteins at the beginning of the experiment. They then injected the mice with a special antibody that harmlessly draws these proteins out of the brain and into the blood, and retested their blood at intervals throughout the experiment.
Within a year, all the animals had developed brain plaques to varying degrees.
Within five minutes of receiving the special antibody, blood samples revealed plaque proteins -- and the amount of protein correlated to the amount of plaque in each animal's brain.
"This has obvious implications for developing a similar blood test for brain [plaque] in humans," says Holtzman. "Though we will not be able to detect risk in someone who has not begun to accumulate [the proteins], we hope to predict the disease well before symptoms appear. Such a test could distinguish individuals suffering from dementia caused by Alzheimer's from those with other types of dementia, and may help us evaluate an individual's response to particular medical therapies," he says.
Medically Reviewed
By Dr. Gary Vogin

Nature Science update
30.Drug saps Alzheimer's
Optimism for chemical that destabilizes harmful protein build-ups.
16 May 2002
HELEN PEARSON

Clinical studies will start within weeks on a new drug(CPHPC) that may erode the protein clumps behind Alzheimer's disease and type II diabetes.
In these diseases, proteins that are usually soluble fold abnormally into tightly packed deposits called amyloid that wreck internal organs. In mice, the prototype drug shrank these protein accretions within weeks, scientists have revealed. Preliminary tests on patients look promising.
"I can't describe how excited I was," says Mark Pepys of University College Medical School in London, who has been working on the idea for the past 25 years. "We've invented a new molecule - and it does what we want."
Leslie Iversen, who studies Alzheimer's at King's College London is also enthusiastic. Clearing away the plaques that clog patients' brains is thought to be key to reversing the nerve damage that causes dementia.
But Iversen suspects the drug will need some modification before it hits the shelf: "It's not a cure," he warns.
Blocker blocking
Pepys' drug targets a protein called serum amyloid P component or SAP. SAP coats amyloid deposits protecting them from being destroyed and removed by the body. "Normal scavenging mechanisms can't get rid of them," explains Iversen.
The team screened 100,000 chemicals for one that stops SAP sticking to amyloid. They developed a molecule that ties two SAP proteins together, which has the added bonus of speeding SAP breakdown in the liver1.
As the drug lowers SAP levels in the blood it strips away any SAP clinging to amyloid deposits. So while the drug cannot penetrate the brain, it can draw out the SAP lodged there and potentially destabilize Alzheimer's plaques.
The team gave the drug to 19 sufferers of systemic amyloidosis for up to nine and a half months. This rare and ultimately lethal condition is caused by widespread protein deposits affecting tissues such as skin and heart.
I can't describe how excited I was
Mark Pepys, University College Medical School, London
To watch SAP move around the body, they injected a radioactively labelled version of the protein which they followed with a whole-body radiation scanner.
Within ten minutes, SAP moved towards the liver. The drug cleared it from the blood after 24 hours. It is too early to say whether these gravely ill patients have improved, but Pepys' unpublished results suggest that amyloid build-ups are eroded.
Building on success
Vaccination against the amyloid protein - one of the most promising Alzheimer's treatment strategies being pursued - received a setback recently when clinical trials were halted because patients developed brain inflammation. Other drugs are being developed that prevent proteins massing into plaques.
But Pepys' molecule could tackle a wide range of diseases. Amyloid accumulates in the pancreas of people with type II, or adult onset, diabetes. People receiving kidney dialysis also suffer from build-up of proteins that dialysis machines cannot filter out.
In theory, the molecule might also alleviate prion diseases, including the human form of mad cow disease, variant Creutzfeldt-Jakob disease (vCJD), which is also caused by misfolded proteins. But amyloid deposits do not always form in these spongiform encephalopathies, so Pepys is cautious about whether the drug is appropriate to treat CJD.

References
Pepys, M.B. et al. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature, 417, 254 - 259 , (2002).

31.Scanning may help detect early Alzheimer's disease
Last Updated: 2002-07-25 11:00:39 -0400 (Reuters Health)

STOCKHOLM (Reuters) - A new brain imaging technique could help doctors detect Alzheimer's disease decades before symptoms appear, scientists said on Thursday.
They also said it could speed up the development of drugs to fight the degenerative brain disorder, which affects around 12 million people worldwide.
In research presented at an international Alzheimer's meeting, scientists from the University of California in Los Angeles (UCLA) said a chemical marker called FDDNP allows doctors to track early changes in the brain.
They used the marker in conjunction with a brain imaging technique called positron emission tomography (PET).
"We found that people with normal memory performance with a genetic risk for Alzheimer's disease had a higher signal on the PET scan than those without the generic risk, indicating that evidence of the disease is apparent even before people have obvious memory symptoms," Dr Gary Small said.
Alzheimer's disease is not apparent until patients develop symptoms such as memory loss and confusion. The disease is marked by the buildup of plaques and tangles in the brain, and usually occurs in people older than 60.
Small and his team used FDDNP, which was developed at UCLA, and PET to pinpoint early signs of the illness. Theirs was one of several studies presented at the meeting looking into new ways to detect Alzheimer's with PET scans.
"What these studies are suggesting is that we can see the physical evidence of Alzheimer's disease decades before people even reach the age at risk," Small explained.
The UCLA scientists studied people with the ApoE-4 gene, which is associated with Alzheimer's. It is one of several factors that may increase the risk of developing the illness.
Small said the technique could have two purposes--as a potential diagnostic tool after it is developed further, and to test the effectiveness of new treatments.
"What's exciting about this new invention is that it offers us a way to test new drugs that could be targeted to clearing out the plaques and tangles and to start testing them in people before they have significant brain damage from Alzheimer's disease," he said.
Alzheimer's is the leading cause of senile dementia. There is no cure for the condition, and drugs can only improve symptoms temporarily. Patients are eventually unable to perform daily tasks and require constant care.
Up to 4,000 scientists and doctors are attending the week-long International Conference on Alzheimer's Disease and Related Disorder in the Swedish capital.

32.Consuming More Calories and Fats May Be Associated With a Higher Risk of Alzheimer Disease
Alzheimer's Association USA

CHICAGO - Eating more calories and fats may contribute to an increased risk of Alzheimer disease (AD) in some people, according to an article in the August issue of The Archives of Neurology, one of the JAMA/Archives journals.
According to background information given, significantly reduced calorie diets have been associated with longer life spans in mice and rats. Researchers believe that the relationship is a result of the production of fewer free radicals, destructive molecules formed during the breakdown of food and oxygen in cells. Free radicals damage cells and may increase the damage done by beta amyloids, the glue-like particles found in the brains of people with AD.
Jose A. Luchsinger, M.D., of Columbia University, New York, NY, and colleagues studied the association between caloric intake and AD in 980 elderly individuals without AD at the start of their study. The researchers followed these patients for an average of 4 years and recorded how many calories they ate and tested for the presence of the apolipoprotein E (APOE) epsilon 4 allele, a gene that has been associated with AD.
During the study, 242 patients developed AD, and 28 percent tested positive for the APOE epsilon 4 gene. The average daily caloric intake of the women studied (67 percent of the study population) was 1,267 kcals. Men consumed an average of 1,316 kcals per day. Average daily fat consumption in both groups was 38 grams.
The researchers divided the study group into four groups depending on how many calories were consumed daily. The group that consumed the most calories had a 50 percent greater chance of developing AD.
The researchers also looked at the effect of the APOE epsilon 4 gene. Of the participants, 263 tested positive for the APOE epsilon 4 gene, and among them, those who consumed the most calories had a 2.3 times greater chance of developing AD compared to those who ate the fewest calories.
The authors write that "Calorie restriction may also decrease [nerve cell] death and increase expression of neurotrophic [nerve-protecting] factors in the brain. Reduced calorie intake can increase the brain's capacity for plasticity and repair in neurodegenerative disorders, including AD."
The researchers conclude: "Our analyses of 242 cases of incident AD... revealed that the risk of AD is associated with higher total calorie intake and fat intake in individuals [with] the APOE epsilon 4 [gene]. In individuals without the APOE epsilon 4 [gene], calorie and fat intake were not associated with risk of AD."
(Arch Neurol. 2002;59:1258-1263. Available post-embargo at archneurol.com)
Editor's Note: This study was supported by grants from the National Institute of Aging, Bethesda, Md., and the Charles S. Robertson Memorial Gift for research on AD, the Blanchette Hooker Rockefeller Foundation, and the New York City Speaker's Fund for Public Health Research, New York, NY.

33.Neurochem Files Investigational New Drug Application For Alzhemed(TM) to Treat Alzheimer's Disease

SAINT-LAURENT, Canada, Aug. 29 /PRNewswire-FirstCall/ --
Neurochem Inc. (TSX: NRM) announced today that it has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration for Alzhemed (TM), the company's lead candidate for the treatment of Alzheimer's Disease (AD). The IND submission precedes the initiation of a Phase II
clinical trial in the United States for patients suffering from mild to moderate stage AD.
"The IND filing for the initiation of Phase II trials for Alzhemed is an important milestone within our Alzheimer's disease program," said Dr. Louis R. Lamontagne, President and CEO of Neurochem. "In planning the Phase II trial, we have adopted a graduated, strategic approach, focusing this trial on
Alzhemed's safety, tolerability and pharmacokinetic profiles in patients. Our objective is to optimize the subsequent North American efficacy trials based on the results obtained in this Phase II clinical study."
A Phase II clinical trial, scheduled to begin in the U.S. this fall, is expected to investigate the safety, tolerability and pharmacokinetic profile of Alzhemed in patients with mild to moderate AD. Specifically, the study is planned to determine optimal dosing regimens for subsequent pivotal efficacy trials. The effect of Alzhemed on the amyloid beta protein (the pharmacological target for drug activity) levels in cerebrospinal fluid and plasma would also be evaluated. The study is designed as a multicenter, randomized, double-blind, placebo-controlled and parallel design study. A total of 48 AD patients would receive placebo or Alzhemed (3 dose levels) for a period of three months.
Neurochem has previously investigated the safety, tolerability and pharmacokinetic profiles of Alzhemed in healthy volunteers in three single dose and one multiple dose Phase I clinical trials involving a total of 117 subjects. In all three studies, Alzhemed was shown to be safe and well tolerated at the anticipated therapeutic dose in both young and elderly volunteers.

About Alzhemed (TM)
Alzhemed is an oral small organic molecule that has been specifically designed to modify the course of the disease by interfering with the association between glycosaminoglycans (GAGs) and amyloid beta amyloid protein. Alzhemed as part of a "disease modifying" class of drug candidates, is expected to act at two levels: to prevent and stop the formation and deposition of amyloid fibrils in the brain and in binding to soluble amyloid beta, to inhibit the inflammatory response associated with amyloid build-up in
Alzheimer's Disease. Its anti-amyloid effectiveness has been demonstrated in an aggressive transgenic mouse model of brain amyloid with a significant 61% reduction in amyloid beta plasma levels and a 30% reduction in amyloid beta brain soluble and insoluble fractions after only 8 weeks of treatment.

About Neurochem
Neurochem is an industry leader in the development of therapeutic drugs and diagnostic tools for central nervous system (CNS) and amyloid-related diseases associated with aging. The Company has to date advanced three drug candidates to clinical trials: Fibrillex(TM), for the life-threatening orphan
disease, secondary amyloidosis in a pivotal Phase II/III clinical trial,
Alzhemed(TM), for the treatment of Alzheimer's Disease advancing to Phase II clinical trials, and Cerebril(TM), for hemorrhagic stroke also advancing to Phase II clinical trials. The Company has built a strong product pipeline by developing a novel, proprietary series of compounds that inhibit the
formation, deposition and toxic effects of amyloid fibrils within the body.
Neurochem's overall therapeutic programs target CNS disorders including Alzheimer's disease, epileptic seizures caused by head trauma or acute brain injury, and hemorrhagic stroke (due to cerebral amyloid angiopathy), and other life-threatening diseases including systemic amyloidosis and amyloid-
associated diabetes type II. (http://www.neurochem.com).

All of the statements contained in this news release, other than statements of fact that are independently verifiable at the date hereof, are forward-looking statements. Such statements, based as they are on the current expectations of management, inherently involve numerous risks and
uncertainties, known and unknown. Some examples of known risks are: the impact of general economic conditions, general conditions in the pharmaceutical industry, changes in the regulatory environment in the jurisdictions in which Neurochem does business, stock market volatility, fluctuations in costs, and
changes to the competitive environment due to consolidation or otherwise.
Consequently, actual future results may differ materially from the anticipated results expressed in the forward-looking statements.

For Further Information, Please Contact:
Dr. Lise Hebert
Director, Communications and Investor Relations & Project Management
lhebert@neurochem.com
Tel: (514) 337-4646
Fax: (514) 337-5339

Nathalie Bourque
National Public Relations
nbourque@mtl.national.ca
Tel: (514) 843-7171
Fax: (514) 843-6976

Karla MacDonald or Jessica Morrison
Feinstein Kean Healthcare
kmacdonald@fkhealth.com or jmorrison@fkhealth.com
Tel: (617) 577-8110
Fax: (617) 577-8985

SOURCE Neurochem Inc.
Web Site: http://www.neurochem.com

34.Senior Homicides A Growing Problem
October 3, 2002
PHILADELPHIA (AP) -- In three months, two elderly Pennsylvania men have allegedly been killed by fellow residents at assisted living facilities. Analysts say the attacks are part of a small but growing problem.

With more Americans living into their 80s and 90s, an unprecedented number of seniors suffering from conditions such as Alzheimer's disease that may make them aggressive have moved into institutions, and assaults on caregivers, relatives and friends are on the rise, experts say.

Roy D. Schrack, 91, died from pneumonia Sunday, five days after he was knocked down by his 83-year-old roommate, who suffers from dementia, at an assisted-living center in Wyomissing, authorities said.

Officials said Schrack suffered a broken hip when the roommate threatened him, grabbed his shirt, causing him to fall, then fell on top of him. A medical examiner ruled the death a homicide, saying complications from the fall led to Schrack's illness.

His death came less than three months after 81-year-old Joseph A. Braun died from injuries sustained in a scuffle with a resident at the Berks Heim nursing home, authorities said. That case was also ruled a homicide.

Prosecutors haven't filed charges in either case. Nursing homes report thousands of incidents of patient-on-patient violence each year. Most of the alleged attacks involve small fights, but even those can lead to serious injury among the very old.

New York and Florida both reported cases last year of nursing home patients being killed by fellow elders suffering from dementia.

"It's not a minor problem, and it's one that, unfortunately, we think we may be dealing with more in the future," said Mark Miller, a policy analyst with the National Center on Elder Abuse.

Nationwide, more than 3,000 complaints about resident-on-resident abuse were lodged with state long-term care ombudsman programs in 2000, up from around 2,500 complaints in 1996.

Analysts said the rise coincides with a growing number of Americans suffering from dementia.

By 2000, some 42 percent of nursing home patients suffered from dementia and 50 percent were taking psychoactive drugs, according to the American Health Care Association, which represents 12,000 mostly for-profit nursing homes. The number of nursing home beds dedicated to Alzheimer's patients nearly doubled in five years, from 50,000 in 1995 to 97,000 in 2000.

Since aggression is one of the common effects of Alzheimer's, some senior advocacy groups have suggested that, despite a deepening understanding of dementia and its causes, many facilities are ill-equipped to handle elders who become violent.

"In some of these residences, there isn't enough staff, there is insufficient training, and there is low pay," said Toby S. Edelman, a lawyer with the Center for Medicare Advocacy. "We need to be careful that we are sending people to places that can care for them appropriately."

Nanne Lewine, a policy analyst for the senior advocacy group AARP, said many nursing homes have done away with policies requiring unruly patients to be put in physical restraints. States have also shied away from committing elders with dementia to mental hospitals, especially those who only exhibit destructive behavior occasionally.

"It seems to be a pretty prevalent problem, but it could be one of those situations where, for the facilities, you are damned if you do, and damned if you don't," she said. "You don't want to throw someone into an institution when they only have problems sporadically. You want to have them live as independently as possible."

BMJ 2002;325:932-933 ( 26 October )
paper
35.Fish, meat, and risk of dementia: cohort study
Pascale Barberger-Gateau, senior lecturer, Luc Letenneur, researcher, Valerie Deschamps, research fellow, Karine Peres, research fellow, Jean-Francois Dartigues, professor, Serge Renaud, researcher.

INSERM U330, Universite Victor Segalen Bordeaux 2, case n°11, 146 rue Leo-Saignat, 33076 Bordeaux Cedex, France

Correspondence to: P Barberger-Gateau Pascale.Barberger-Gateau@isped.u-bordeaux2.fr

The role of dietary fat in dementia arouses increasing interest.1 Fatty acids could be involved through several mechanisms, including atherosclerosis, thrombosis, and inflammation.2 We evaluated whether there is a relation between consumption of fish (rich in polyunsaturated fatty acids) or meat (rich in saturated fatty acids) and risk of dementia.

Participants, methods, and results
We obtained data from the PAQUID (Personnes Agees QUID) epidemiological study of cognitive and functional ageing (www.healthandage.net/html/min/paquid/entrance.htm). During the third wave of the study (1991-2) investigators visited 1674 people aged 68 and over without dementia and living at home in 75 parishes in southwestern France and recorded their frequency of consumption of meat and fish or seafood: daily, at least once a week (but not every day), from time to time (but not every week), never. Participants were followed up two, five, and seven years afterwards: 1416 (84.6 %) had at least one follow up visit. All the participants who had lost three points or more on the mini-mental state examination since a previous visit or were suspected of having dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) were visited by a neurologist to confirm the diagnosis.
We calculated the incidence of dementia per 100 person years. We used a Cox proportional hazards model with delayed entry to estimate the relative risk of dementia, taking into account age, sex, and education (at least the French primary school diploma "Certificat d'Etudes Primaires" versus less education3).
During the seven years of follow up 170 new cases of dementia occurred, including 135 cases of Alzheimer's disease. The table shows a significant trend between increasing consumption of fish or seafood and decreasing incidence of dementia (P for trend=0.0091). Frequency of fish or seafood consumption was higher in the participants with higher education (879/1051 (83.6%) v 262/365 (71.8%) consuming fish at least weekly; P<0.0001). Participants who ate fish or seafood at least once a week had a significantly lower risk of being diagnosed as having dementia in the seven subsequent years (age and sex adjusted hazard ratio 0.66, 95% confidence interval 0.47 to 0.93). When we added education into the model the hazard ratio was almost unchanged (0.73) but the 95% confidence interval (0.52 to 1.03) slightly overlapped 1.00, indicating that the "protective" effect of weekly fish or seafood consumption was partly explained by higher education of regular consumers. Participants who ate fish or seafood at least once a week had a hazard ratio, adjusted for age and sex, of 0.69 for developing Alzheimer's disease in the seven following years, with borderline significance (95% confidence interval 0.47 to 1.01). We found no significant association between meat consumption and risk of dementiaP for trend=0.59; age and sex adjusted hazard ratio for weekly consumers 0.56 (0.26 to 1.20).

Comment
Elderly people who eat fish or seafood at least once a week are at lower risk of developing dementia, including Alzheimer's disease. The Rotterdam study found similar results but had a much shorter follow up (mean 2.1 years).4 Given that the first consequences of dementia on everyday living can appear three years before diagnosis,5 poor dietary habits could be a consequence rather than a cause of cognitive decline in the Rotterdam participants.
In addition to providing vascular protection, the n-3 fatty acids contained in fish oils could reduce inflammation in the brain and may have a specific role in brain development and regeneration of nerve cells.2 Healthy dietary habits acquired in infancy could be associated with achievement of higher education. Highly educated people might also adhere more closely to dietary recommendations on fish consumption.

Reuters Health Information (2002-10-25):
36.Brain fluid drain studied as Alzheimer's therapy
Brain fluid drain studied as Alzheimer's therapy
Last Updated: 2002-10-25 12:15:55 -0400 (Reuters Health)
NEW YORK (Reuters Health) - An investigational treatment designed to improve the circulation of the fluids bathing the brain and spine could be a feasible therapy for Alzheimer's disease, results of a pilot study suggest.
However, researchers caution that it is too early to say whether the therapy--in which an implanted shunt drains small amounts of cerebrospinal fluid (CSF) from around the brain--will become a weapon against Alzheimer's.
CSF fills the spaces around the brain and spinal cord, and it is naturally produced, absorbed, then replenished by the body. With age, however, this normal CSF circulation diminishes. The experimental shunt therapy is based on the hypothesis that helping CSF drain from the skull might shuttle away proteins associated with Alzheimer's brain damage.
Alzheimer's disease is marked by two types of abnormal brain deposits--"plaques" composed of amyloid beta proteins and "tangles" made up of tau proteins. Some researchers speculate that the soluble concentrations of these proteins in CSF may influence the levels in a person's brain. For example, the authors of the new study note, some Alzheimer's patients have been found to have low amyloid beta levels in CSF samples, which could be the result of poor "clearance" of the proteins from the brain.
To begin to test this idea and the usefulness of CSF drainage, Dr. Gerald D. Silverberg and his colleagues compared 15 Alzheimer's patients who had a shunt implanted with 14 who did not have the surgery. They found that over 1 year, mental functioning scores remained fairly stable among the shunt patients, but declined among the other study participants.
Silverberg, a researcher at Stanford University in California, and his colleagues report the findings in the October issue of Neurology. The Redwood City, California-based Eunoe, Inc., which makes the shunt under the name
Cognishunt, funded the study.
The investigators point out that the study was too small to conclude that the shunt actually slowed patients' mental deterioration. However, they did detect changes in the levels of tau and amyloid beta in the CSF drained from patients' brains--suggesting, Silverberg's team explains, that improving CSF circulation may help slow the progression of Alzheimer's by boosting the clearance of substances toxic to the brain.
But whether this is the case is far from clear, according to an editorial accompanying the report.
"The authors do not advocate shunt treatment for Alzheimer's disease at this time. We strongly concur," write Dr. David A. Bennett of Rush Alzheimer's Disease Center in Chicago, Illinois, and Dr. Michael P. McDermott of the University of Rochester in New York.
They note that although this pilot study had an "interesting" rationale, it is still unclear whether CSF drainage actually influences the movement of amyloid and tau from the brain.
They also point to the risks of the shunt, which is set up to drain fluid from a brain ventricle, or cavity, and into the abdomen. In this study, two patients had seizures, one developed an infection, and one sustained a small tear to the
bowel during surgery--although all these complications were successfully managed. In three patients, the shunts became blocked.
According to Silverberg's team, a larger clinical trial of the shunt therapy is now under way.
SOURCE: Neurology 2002;59:1126-1127, 1139-1145.

CNN.com
37.New scans show Alzheimer's in a living brain
Sunday, January 12, 2003 Posted: 8:59 AM EST (1359 GMT)

(AP) -- Some doctors would enjoy nothing more than poking around inside your brain. First they would give your frontal cortex a thorough going-over. Then maybe they would take a peek at your temporal lobes. Finally, they would confidently predict whether in five or 10 or maybe even 20 years you will lose the whole works to Alzheimer's disease.

Not that you would want to know this, necessarily, since nothing can be done yet to stop the disease. Still, doctors appear surprisingly close to getting their wish.
Experimental new technology is opening a window on the living human brain, catching the first clear look at the mess Alzheimer's makes as it happens.
It builds on the standard imaging machines, such as PET scanners, that are sometimes used on people with suspected Alzheimer's disease. Those can reveal whether parts of the brain are shrunken, as occurs in Alzheimer's, or work sluggishly. But short of cutting open the skull, there has been no way to reveal the disease itself, to tease out the errant gummy proteins that distinguish Alzheimer's from normal gray matter.
Until now. The new approach is also a PET scan, but unlike anything now available, it lights up these misplaced proteins. Scientists can look at pictures of cross-sectional slices of the brain, and for the first time, they can say: That's Alzheimer's. They can see it creeping insidiously, inexorably across the places that control memory, reasoning and everything else that makes us who we are.
"It's an incredible first step," says Neil Buckholtz, dementia chief at the National Institute on Aging.

Solving the puzzle
Two competing teams in Pittsburgh and Los Angeles have produced these scans in the past year, using similar methods. No one knows whether either approach will make it into routine use. But many believe something like them eventually will.
"They are both really magnificent examples of how far the technology has come," says William Thies, the Alzheimer's Association's medical director. "Here we have the ability to actually image something in the human brain that previously could only be seen in an autopsy."
Ordinary PET scans trace radioactive sugar as it moves through the brain, revealing how vigorously it is used in various parts. While this offers clues to how well the brain functions, it says little specifically about Alzheimer's.
For that, doctors must examine slices of brain under a microscope. Seen there, the disease has an unmistakable signature -- deposits of protein fragments called beta amyloid that fill up the spaces between brain cells and probably somehow contribute to their death. This amyloid plaque is easy to spot because it avidly absorbs a textile dye called Congo red.
But revealing amyloid in a living brain is another matter, since it's invisible on an ordinary brain scan. For years, researchers have puzzled over how they could introduce an amyloid-seeking chemical into someone's head so it would show up on these scans. Ideally, Congo red could be bonded with a radioactive isotope, injected into the blood and then watched as it travels through the brain. If it accumulates somewhere, bingo, that's amyloid.
However, like many chemicals, Congo red does not cross into the brain from the bloodstream, so that won't work. Seven years ago, Chester Mathis, a radiochemist, and Dr. William Klunk, a psychiatrist, teamed up at the University of Pittsburgh to find something that would.
They started out with Congo red, hoping to make it enter the brain by taking away its electrical charge. It was slow going. Eventually, they moved on to other dyes, including one called thioflavin T.
"We removed the charge," says Mathis. "Lo and behold, not only does it get into the brain, but it's even more potent than the parent dye in binding to amyloid." Much tinkering later, including testing on mice and baboons, the team created Pittsburgh Compound B, a radioactive dye ready to try on people.

Dye-ing to be useful
That happened last winter at Uppsala University in Sweden. Doctors injected the dye into 14 volunteers. Nine had early stage Alzheimer's. The rest were normal. Each took a 90-minute turn inside the PET scanner.
To be useful, the dye had to do more than stick to the volunteers' amyloid. It also had to avoid most everything else inside their brains. As the researchers went over the scans, they found no dye in the cerebellum. That was an encouraging sign, since amyloid doesn't accumulate there.
Furthermore, the scans showed little accumulation in the healthy volunteers. But the Alzheimer's patients were clearly different. On the scans, the dyed amyloid shows up tomato red and yellow. The colors ooze ominously across the frontal cortex and the temporal and parietal regions.
"When I saw it for the first time, I felt like, 'Wow, there it is,'" says Klunk. "There is amyloid in the brain. You're looking at it, after trying for so long."
At an Alzheimer's conference last July in Stockholm, the Uppsala scans were shown in public for the first time. Klunk and Mathis were sitting in the audience as the images with their dramatic red and yellow blotches filled the screens.
"Several thousand people were in the auditorium, and they gasped," remembers Mathis. "It was exactly what pathologists see when they apply stains to human tissue. Everybody realized it was in the right places."
The Pittsburgh team's main competition is a group at UCLA headed by Jorge Barrio, a pharmacologist, and Dr. Gary Small, a psychiatrist. They have developed a synthetic chemical called FDDNP and tagged it with radioactive fluorine-18 so it will show up on PET scans. Plaque is hydrophobic, meaning it resists water, and FDDNP is designed to home in on any hydrophobic tissue.
In testing on about 70 older people, their scans show buildups of hydrophobic material, presumably plaque, in areas of the brain where it is known to accumulate during Alzheimer's disease. However, finding people with obvious Alzheimer's is unlikely to be the most important use of any such brain scan.
"This is driven by the idea that it will probably be easier to protect the brain before it's damaged than to repair damaged cells later, so let's find it as soon as possible," says Small.
Among their elderly volunteers, the UCLA researchers say, were several chosen because they seemed free of the disease. But in two of them, the scans showed apparent plaque. More careful evaluation revealed they had memory problems. Perhaps the scans had picked up early-stage Alzheimer's
"This is driven by the idea that it will probably be easier to protect the brain before it's damaged than to repair damaged cells later, so let's find it as soon as possible," says Small.
Among their elderly volunteers, the UCLA researchers say, were several chosen because they seemed free of the disease. But in two of them, the scans showed apparent plaque. More careful evaluation revealed they had memory problems. Perhaps the scans had picked up early-stage Alzheimer's
The problem is proving any of them work. Alzheimer's symptoms vary from person to person. Often the disease progresses slowly. It could take several years of testing to prove that a drug has any effect on memory and reasoning. Even then, assessing changes in symptoms will be a judgment call.
"No CEO will commit to what will be a long, large, expensive trial when there is no decent endpoint," says Dr. Samuel Gandy, director of the neurosciences institute at Thomas Jefferson University.
Offering such an endpoint could be the first big use of the new scans. Experts envision testing an amyloid drug on a dozen or two volunteers, then following them for a few months to see if it changes the amount of amyloid on their brain scans. If it does, then developers would feel more confident taking the drug into large-scale testing to see if it slows symptoms, too.
In fact, the scans will allow the ultimate challenge of the central dogma of Alzheimer's disease -- whether amyloid plaque truly is an essential culprit in the progression of the disease or whether it's simply a byproduct of it.
"The major question is, If you get rid of the plaque, will that help your cognition?" asks Buckholtz. "And if you prevent it from forming, will that prevent the disease?"

A routine brain scan
But if amyloid plaque truly is a cause of Alzheimer's disease and if brain scans can spot it early, then some experts envision someday routinely giving the scans to people in their 60s, 50s or even their 40s, especially if the disease runs in their families.
Studying people with scans at various ages should help doctors learn when amyloid starts to build up, how it moves across the brain and what amount causes symptoms. Do some people escape the disease even with large amounts of amyloid? And if so, does it matter which parts of their brains are involved?
Like many people, Klunk has a fantasy about what he will do on his very last day at work.
"Here's how I'd like to retire," he says. "Somebody comes into my office, 65, parents had Alzheimer's. I send him out for a scan. Either I say, 'There's nothing there.' Or 'You have the earliest stages of amyloid deposition. It's no big deal. Start on anti-amyloid drugs. Don't worry.' That's where I'd like to end."

The Global and Mail
38.Nicotine enhances memory, study finds

By STEPHEN STRAUSS

Friday, January 17, 2003 - Page A8

While sucking on a cigarette definitely is bad for your health, numerous non-smokers may find themselves some day being prescribed nicotine patches to combat Alzheimer's disease.
In a soon-to-be-published study, scientists in North Carolina will describe how they tested the patches on 11 senior men and women to counter deteriorating memories.
After several weeks of treatment, the subjects experienced significant improvements in their abilities to make decisions quickly and recognize objects.
The researchers are so impressed with the results that they propose a long-term, multisite study involving a large number of seniors whose memories are frayed.
As well, researchers at the University of Manitoba have published material detailing nicotine's ability to combat the effects in nerve cells of one of the substances believed to cause Alzheimer's.
"The concept is the same as the effect of Aspirin on inflammation," said Daniel Sitar, lead U of M researcher.
U.S. and European studies published over the past year indicate that nicotine has a protective effect in laboratory animals whose conditions mimic those resulting from Alzheimer's.
Said Paul Fraser, a researcher with the Centre for Research in Neurodegenerative Diseases at the University of Toronto, "The definitive animal experiment has already been done in Sweden."
All this research reinforces the results of small studies on humans by Edward Levin at Duke University's Medical Center laboratory, which found that using nicotine patches on people with Alzheimer's reduced some of their mistakes by 10 to 80 per cent.

Despite the encouraging data, some researchers are concerned that the public might misinterpret the results.
In particular, they fear that some will conclude smoking is beneficial.
"By no means am I encouraging anyone to take up smoking or to continue smoking because clearly the adverse consequences of smoking outweigh any cognitive improvement," Prof. Levin said.
Ken Kellar, a Georgetown University professor in Washington, who hopes to collaborate with Prof. Levin on the large study, noted: "Smoking cuts life expectancy by seven or eight years, and some would argue that that is a way of getting rid of Alzheimer's patients before they come down with the disease."
Still another cause for going slow is confusing epidemiological data.
Initially, it was thought that half as many smokers as non-smokers came down with Alzheimer's.
But several recent analyses of Alzheimer's data has turned up neither a positive nor a negative connection.
But proponents of nicotine as a brain medicinal argue that this shows only that the bad features of smoking cancel any good effects of nicotine.
Some scientists said a lack of funding is part of the reason there have been no large trials examining the nicotine-patch effect on a disease such as Alzheimer's.
Because nicotine is in the public domain, the drug's new medical uses cannot be patented.
"We could have had answers 10 years ago to the question of whether it is good for Alzheimer's if drug companies had given a go on it," Prof. Kellar said.
Instead, several drug companies are trying to develop nicotine look-alikes that they can patent, Prof. Levin said.
The arrival of these look-alikes or a test proving the long-term efficacy of nicotine patches for elderly patients is some time away.
"It's really heart-rending when you get a call from someone who wants to know whether to use the patch, and you have to say [that] in a couple of years we will have a better answer for you," Dr. Levin said.
"It's especially hard when they say, 'But my grandmother has Alzheimer's now.'

Ｈerald Sun(Feb. 5,2003)

39.Low testosterone, dementia link

MEN with low levels of testosterone may be at risk of developing brain diseases like dementia and Alzheimer's in later life.
Alzheimer's usually occurs after the age of 65, causing serious damage to neurons in the brain.
It is heralded by progressive memory loss, confusion and ebbing of higher brain functions.
A study of West Australian men released by a testosterone replacement centre today supported earlier Australian and overseas research linking low levels of testosterone with a risk of developing Alzheimer's, the founder of the Well Men Centre said.
Linda Byart said the unpublished research was based on 100 men between the ages of 29 and 80 who attended the centre with low levels of testosterone.
Ninety-six per cent of the men experienced "loss of interest mentally and loss of motivation" and 85 per cent suffered memory loss, lapses in concentration and loss of mental clarity.
The subjects all had testosterone levels below 12 nmols, with is accepted as low by the American Association of Clinical Endocrinologists.
In Australia, levels of less than 8 nmols are accepted as low by the Pharmaceutical Benefits Scheme (PBS).
The findings follow a recent conference in London which examined the relationship between the male hormone and the brain, and the potential role of testosterone in preventing dementia.
One of the presenters was Dr Ralph Martins of the Sir James McCusker Alzheimer's Disease Research Unit at the University of Western Australia.
Dr Martins' group led the world in establishing a protein called beta amyloid as a major culprit in Alzheimer's disease.
When beta amyloid deposits build up in the brain they clog neural tissues, killing brain cells en masse.
Early studies had shown a "very strong association" between low testosterone and high levels of beta amyloid, Dr Martins said.
Laboratory tests in the US also indicated that testosterone blocked the toxic effects of beta amyloid.
"It appears to have a two-pronged effect though its major function appears to be reducing the level of amyloid," he said.
Dr Eva Hogerhorst from England's Oxford University told the conference that researchers from the Oxford Project to Investigate Memory and Ageing had found lower levels of testosterone in men with Alzheimer's.
"Sex steroids such as testosterone and estradiol have been found to potentially protect the brain against Alzheimer's disease," she said.
In 1995, the Australian Bureau of Statistics estimated that either Alzheimer's disease or a related dementia afflicted 130,000 Australians.
During the next 40 years, its incidence is predicted to increase 254 per cent in Australia.

ITV,com(Fe.5 2003)

40.Mobile phones in Alzheimer's scare

Researchers claim there may be a link between the use of mobile phones and the early onset of Alzheimer's disease.
Scientists have discovered that prolonged exposure to mobile handsets can destroy cells in the parts of the brain responsible for memory, movement and learning.
Three years ago, an investigation by Sir William Stewart claimed that there was no evidence of a health risk associated with the use of mobile phones.
But the new research, from Lund University Hospital in Sweden, links the use of mobiles with damage to the neurons in the brain.
The study looked at the effects of radiation on laboratory rats, who were bombarded for two hours with radiation equivalent to that from mobile phones.
Professor Leif Salford said: "The reason for our choice of 12-26 week-old rats is that they are comparable to human mobile phone-addicted teenagers.
"Damage of the neurons of this kind may, in the long run, result in reduced brain capacity.
"We cannot exclude that after some decades of (often), daily use, a whole generation of users may suffer negative effects in middle age."
However, a spokesman for the Mobile Operators Association dismissed the results of the research, claiming "the weight of scientific evidence suggests" that exposure to radio waves within international guidelines does not cause health problems.
Lawrence McGinty, science editor of ITV News, said: "I am not worried. I am still using my mobile.
I don't think we should be worried by this research in itself, but I think it should prompt further extended research to see if there are any problems."

San Luis Obispo.com( Feb. 04, 2003)

41.Holocaust survivors with Alzheimer's can relive old horrors

BY TOM MCCANN Chicago Tribune

CHICAGO - KRT NEWSFEATURES
(KRT) - Hela Fisk hides bread in cubbyholes in her bedroom. She becomes frightened if nurses mention the word "shower." At 89 and stricken with Alzheimer's disease, the petite grandmother of five relives the horror of the Holocaust as though it were happening now.
Fisk and thousands of Chicago-area Jews who endured the Nazi purges have entered their 80s and 90s, and many now find themselves in health care facilities, struggling each day with age-related dementia. Their minds can no longer keep buried the tortured memories of concentration camps, gas chambers and loved ones killed before their eyes.
Compounding the problem, many of the things that spark vivid flashbacks are found in hospitals and nursing homes: white lab coats, restraints and locked doors, antiseptic smells, people yelling in pain. In addition, many Holocaust survivors underwent excruciating experiments at the hands of German doctors.
So for the last four years, a group of Chicago-area social workers has been training nursing home employees - some of whom know little about the Holocaust - to understand what the survivors are going through and offer tips on how to avoid triggering bad memories and violent reactions.
Though the needs of aging Holocaust survivors have sparked discussions among geriatrics researchers and care providers around the world, this systematic approach is fairly recent. David Bier of the Council for Jewish Elderly said health care professionals in the Chicago area began to notice symptoms particular to Holocaust survivors in the early 1990s.
As the problem grew, the council and other Jewish agencies decided four years ago to create the Holocaust Community Services program, which visits dozens of nursing homes in Chicago and the suburbs, giving history lessons and sensitivity seminars to everyone from nurse's aides to cooks and dishwashers.
"All it takes is something little to provoke a flashback," Bier said. "It might be the sight of a military uniform. Or it might be a loud, confrontational voice."
At one retirement home a few years ago, a young nurse started putting patients' wheelchairs in a row and telling them they were being lined up for the showers, Bier said. One woman, a Holocaust survivor, became combative and tried to flee, though the aide had no idea why.
"For a person during the Holocaust, going to the shower meant going to the gas chambers. The memories are so traumatic, many can't even bear to hear the word," Bier said.
Many nursing homes now give them baths, and others decorate shower stalls with flower and cartoon decals.
Another common occurrence is the hoarding of food in pockets and drawers and under mattresses, as if hiding it from soldiers, Bier said. If a worker tries to take the food away from them, they often lash out.
"We tell the employees to just give them some space, let them keep the food," Bier said. For perishables like fruit or bread, you can quietly replace them with canned goods. They just want the safety of having it there."
Dr. Michael Gordon, the head of geriatrics and internal medicine at Baycrest Centre for Geriatric Care in Toronto, said he has treated hundreds of such cases among Holocaust survivors and sees more each day.
"During Alzheimer's you revisit the past, and Holocaust survivors have a pretty awful past," Gordon said. "They may have tried to compartmentalize it or forget it, but with age that coping mechanism begins to fail."
Rabbi Marvin Hier, dean of the Simon Wiesenthal Center in Los Angeles, a Jewish human rights organization, said it is simply a different version of what many survivors have lived with for decades.
"Even 50, 60 years later, those horrors never leave you, they're always fresh. The majority of survivors suffer nightmares even when completely healthy," Hier said. "So as they get older and more medically vulnerable, reigniting those memories gets even easier."
At the Gidwitz Place nursing home in Deerfield, Ill., this month, about 50 employees gathered around a big-screen TV to watch black-and-white footage of mass graves, death marches and Jewish prisoners gaunt with starvation. Bier then led them in discussion for more than an hour.
For many, it was their first glimpse of the Holocaust. Immigrants from Haiti, China, the Philippines and Mexico, they were never exposed to it in school.
"Just a little education is all you need," said Ann Hartman Luban, director of Holocaust Community Services. "Once they see these images, they understand."
Darius Brauel, 36, has been an orderly at Gidwitz Place for three years. He said he has to be especially careful because he has a German accent.
"At first I just couldn't figure out why this person was so frightened of me," he said. "But then I found out she survived the Holocaust. It was my accent. Now I just try to speak softly, give the person a chance to calm down. Being nice will always win them over."
At Lieberman Geriatric Health Centre in Skokie, employees have taken part in the training since its launch in 1998. Social service director Jo Hammerman keeps plastic dolls on hand for women who might have lost children in the concentration camps. One nurse climbs into bed with a patient and hugs her to get her out of bed in the morning, she said.
"When Alzheimer's takes away their short-term memory, they live through World War II all over again, worrying about their families, crying for their babies," Hammerman said. "The nurses know not to argue. Instead, we get into their reality, try to make them feel better. It's called therapeutic fibbing."
Rose Sharon, 48, goes to Lieberman every day to visit her mother, Hela Fisk, who has flashbacks so intense she trembles, shouts and sometimes begins swinging at people around her.
Fisk spent years in a Jewish ghetto in Poland. When her family was found hiding, her husband and 5-year-old son were killed by Nazi soldiers, and she was shipped to a forced labor camp.
"She never spoke about that camp. It was just too painful," Sharon said.
Fisk immigrated to New York after the war and married another Holocaust survivor, Stephen Fisk. In the 1960s he developed a brain tumor related to his war injuries, and his mind became trapped in the Holocaust, Sharon said. He sometimes confused his young children for children he had lost in the war; he would make the family stow away food and force the children to hide beneath their beds. He eventually had to be hospitalized.
"My mom went through so much. She kept it all inside. Then her mind started to go a few years ago and things just started rushing to the surface," said Sharon, who moved her mother here from Manhattan in 1998. "She was hoarding piles of food in her apartment. She was getting afraid of other people."
Fisk's nurses and aides try to give her time to herself when the flashbacks hit, rather than struggling to stop them, avoiding confrontations that could further provoke her. Most of the time, they say, she is in great humor.
"You just have to treat her right. Give her time to cool off," said nurse's aide Gloria Ortiz, 45. "The smell of coffee brings her out of it or talking about fashion and dresses. Little by little, she gets back to her old self. She starts smiling again."
Sharon said she made a great choice in sending her mother to Lieberman Centre and appreciates the employees' Holocaust training.
"It's just wonderful to know that they understand my mother," she said. "I really worry about her, and the care she gets here helps me sleep at night."

Thursday, March 27, 2003
42.Study: Silent strokes increase risk for Alzheimer's

(AP) -- Here's another good reason for healthy living: Symptomless, unnoticed strokes more than double the risk of developing Alzheimer's disease, according to a large Dutch study.
The researchers and other experts said the finding suggests many people could prevent the mind-robbing disorder by keeping their heart and blood vessels healthy by exercising, eating a balanced diet and quitting smoking.
Elderly people who suffered tiny "silent strokes" -- detected by an MRI -- had their mental function decline more sharply and were about 2.3 times more likely to develop Alzheimer's or other types of dementia, researchers at Erasmus Medical Center found.
The study, the first major one on silent strokes, was published in Thursday's New England Journal of Medicine.
The work provides "very powerful confirmation" of evidence linking narrowed blood vessels in the brain, stroke and Alzheimer's, said Bill Thies, vice president for medical and scientific affairs at the Alzheimer's Association.
"This is an extraordinarily well-done study in a big group of people," Thies said. "They have identified an outcome from these small (strokes) that we wouldn't have suspected."
In an editorial, Drs. John Blass and Rajiv Ratan of Cornell University's Weill Medical College said the study and other evidence indicate inadequate blood flow in the brain is an underlying cause of both Alzheimer's and stroke -- and that silent stroke may be the first sign of Alzheimer's, not just a risk factor.
Silent strokes are fairly common in the elderly, based on MRI scans of the 1,015 people aged 60 to 90 in the study, said lead investigator Dr. Monique Breteler, head of the Erasmus center's neuroepidemiology research group.
The scans, performed in 1995 and 1996, found brain cell damage in 217 people that indicated a silent stroke. Over an average of 3.6 years of follow-up, 3 percent, or 30 people, developed dementia; 26 had Alzheimer's and four had other forms.
A stroke is a "brain attack" in which the flow of blood and oxygen to part of the brain is interrupted. Most often, it is caused by a blood clot or a hardening of arteries in the brain that cuts off blood flow; this type of stroke, called an infarct, was examined in the study.
Damage from a stroke, such as difficulty speaking or weakness in a limb, varies with the stroke's location and severity. But mental function often declines.
In dementia, mental ability usually declines gradually, impairing memory, learning skills, judgment and attention span. Alzheimer's disease, which also is linked to excessive buildup of proteins in the brain, accounts for about two-thirds of dementia cases.
Eliminating risks
Along with following the 1,015 patients to see who developed dementia, the researchers did a second MRI on 619, some of whom had had additional silent strokes. Mental decline was even more severe in those people, as well as those who had lesions deep inside the brain from narrowed blood vessels, Breteler said.
Because many people who did not undergo a second MRI were in poorer shape mentally, Breteler said, the researchers probably underestimated how much silent strokes increase risk of dementia.
Many people with Alzheimer's have standard risk factors for stroke and heart disease. Those include elevated blood pressure, cholesterol and blood sugar levels; eating a diet high in fat and low in vegetables; smoking; and getting little or no exercise.
Getting the elderly to follow health guidelines to reduce or eliminate those risk factors could prevent dementia or strokes, Breteler said.
Blass and Ratan suggested the same steps for any patients found to have had a silent stroke. They also recommended such patients be monitored by doctors and take baby aspirin every day.
"It's another reason for keeping your cardiovascular system healthy," said Dr. Patrick Pullicino, chairman of neurology and neurosciences at University of Medicine and Dentistry of New Jersey in Newark. "This is simple, common sense."
Pullicino, who is running a 70-center study on preventing stroke and death in heart patients, said there is evidence of mental impairment in elderly people with heart failure, in which the heart can't pump enough blood and oxygen to the brain and body.
He said when an MRI shows a patient has had a silent stroke, doctors must determine the cause and aggressively treat it to prevent a second stroke.

Mon Apr 14, 5:54 PM ET Add Health - Reuters to My Yahoo!
43.Aluminum in Drinking Water Tied to Alzheimer's

By Jacqueline Stenson
SAN DIEGO (Reuters Health) - Adding support to a controversial theory linking aluminum with Alzheimer's disease (news - web sites), new research indicates the disease is more common in regions of northwest Italy where levels of aluminum in drinking water are highest.
And when the investigators studied the effects of one form of the metal on two types of human cells in the lab, they found it hastened cell death.
"We were absolutely surprised by these results," said study author Dr. Paolo Prolo, a researcher at the University of California at Los Angeles. "I did not expect any effect from aluminum."
In findings released here Monday at the annual Experimental Biology meeting, Prolo and colleagues focused on monomeric -- single molecule -- aluminum. This is the type that can be most easily absorbed by human cells, he said.
While there have been suggestions that aluminum cookware might pose a risk for Alzheimer's, the type of aluminum used in pots and pans consists of multiple molecules and does not appear to affect human cells, according to Prolo. "There is almost no evidence that the cookware is dangerous," he said.
When the researchers tested water in regions of northwest Italy in 1998, they found that total aluminum levels -- including monomeric and other types of aluminum -- ranged from 5 to 1,220 micrograms per liter, while monomeric aluminum levels alone ranged from 5 to 300 micrograms per liter.
Environmental officials generally recommended that total aluminum levels be below 200 micrograms per liter, Prolo noted.
After comparing this data to death rates from Alzheimer's in those regions, the researchers found that the disease was more common in areas with the highest levels of monomeric aluminum.
Back in the lab, Prolo and colleagues then tested the effects of monomeric aluminum on human immune-system cells and bone cancer cells. Ideally, human brain cells would be tested but these are not readily available because a biopsy of a patient's brain is necessary to acquire them, he said.
"We found that a very low quantity of aluminum added to our cell cultures was modifying cellular processes" like normal cell death, Prolo told Reuters Health.
When the aluminum was paired with beta-amyloid, a protein found in the brains of Alzheimer's patients, the combination killed off even more cells.
Because aluminum could kill both types of human cells, these findings raise the question of whether aluminum is potentially involved in other diseases, Prolo said.
But much more research is needed to understand how the metal does or does not affect people, he added.

44.Memantine Adds Benefits to Donepezil Therapy in Alzheimer's Patients
By Roberta Friedman, PhD

BALTIMORE, MD -- May 21, 2003 -- Adding memantine to donepezil provides therapeutic benefit over treatment with donepezil alone for people with Alzheimer's disease, according to findings reported here on May 16th at the Annual Meeting of the American Geriatrics Society.
The drug is approved for use in Europe. Food and Drug Administration is expected to make its decision known about the drug's U.S. approval this fall.
Memantine modulates NMDA receptors. "It was a pleasant surprise to see this degree of effect" from the agent, said investigator Pierre Tariot, MD, of the departments of psychiatry, medicine, and neurology, University of Rochester, New York.
A trial at 37 medical centers in the US examined safety and efficacy of memantine for 24 weeks. The study randomised 403 patients in equal numbers to either placebo or memantine at 10 mg twice a day, added to established therapy with donepezil.
Patients had to be taking donepezil for 6 months prior to enrollment, and donepezil dosing had to be stable for the previous 3 months. On average, the patients had been taking donepezil for 2 years.
Mean score on the Mini Mental State Exam at entry was 10, consistent with moderate to severe Alzheimer's disease. "At a time when you expect to see them declining," said Dr. Tariot, family will say patients "are more like themselves," more alert, less apathetic.
Two measures of cognitive function displayed improvement by Week 24 after memantine was added. The Severe Impairment Battery test of cognitive performance showed better results for patients taking the two active drugs, compared to those taking donepezil and a placebo (P<0.001). The Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC-plus) test, a global assessment, also showed the superior outcome achieved with the combination therapy compared to adding donepezil plus placebo (P=0.027).
Significantly less decline on the daily function assessment test, Alzheimer's disease Cooperative Study Inventory - Activities of Daily Living (ADCS-ADL), also were observed when memantine was added to donepezil (P=0.028).
Drop out rates were higher in the group that received donepezil plus placebo, at 25%, compared to 15% for those taking both active drugs.
"Is it safe if you combine the two [agents]? The answer, is a resounding 'yes'," said Dr. Tariot.
Forest Laboratories, Inc. funded the study.

[Study title: Memantine/Donepezil Dual-Therapy is Superior to Placebo/Donepezil Therapy for Treatment of Moderate to Severe Alzheimer's Disease. Abstract P542]

Japantoday
45.Team develops Alzheimer's vaccine without side-effects
Tuesday, June 17, 2003 at 09:00 JST

NAGOYA - A research team at a state-run institute in Aichi Prefecture said Monday it has discovered a vaccine to treat and prevent Alzheimer's disease without causing side-effects.
Hideo Hara and other members of the team at the Chubu National Hospital's National Institute for Longevity Sciences in Obu city found the oral drug did not cause side-effects in mice and was effective administered once every six months.
The team members said they will announce their finding "as an epoch-making treatment method" at a meeting of the Japan Gerontological Society to take place from Wednesday to Friday in nearby Nagoya.
Alzheimer's is a degenerative disease of the central nervous system characterized by premature senile mental deterioration. It is caused by accumulation of excessive amounts of beta-amyloid proteins which affect the brain tissue and lead to atrophy of the brain.
In the team's experiment, the vaccine, which is a virus whose genes have been recombined so it would artificially create beta-amyloid proteins, was fed to the mice.
As a result, an antibody produced in the mucous membranes of the intestines moved to the brain and removed the beta-amyloid proteins that had become attached to the brain, preventing them from accumulating, team members said.
They used mice that were 45 weeks old - equivalent to humans in their 70s - and made prone to developing Alzheimer's disease, gave them the vaccine once, and then checked their brain 11 weeks later.
Normally, accumulated beta-amyloids make up about 2.5% of the brain of such 56-week-old mice, but those that received the vaccine had only about 0.5% of their brain covered by the protein, according to the team.
Fifteen-week-old mice, equivalent to people in their 30s, that were given the vaccine also showed almost no accumulation of the protein in their 56th week from birth.
The team is planning to test the treatment method on aged monkeys by the end of this year with the hope of conducting clinical testing on humans around summer next year.
University of Tokyo professor Yasuo Ihara said the team's study is "significant" as the biggest issue so far in developing medical treatment for Alzheimer's disease had been how to curb side effects of the medicine.
"From now on, the big issue will be how well to fill the gap between mice and humans in the course of clinical trials," Ihara said.
A U.S. pharmaceutical firm developed a vaccine for Alzheimer's in 1999, involving injecting a virus under the skin, but of some 350 patients on whom the treatment was administered, 15 developed brain fever as a side-effect and the vaccination was stopped. (Kyodo News)

46.Mind Games May Trump Alzheimer's Study Cites Effects Of Bridge, Chess

By Shankar Vedantam
Washington Post Staff Writer
Thursday, June 19, 2003; Page A01

Playing chess, bridge or a musical instrument significantly lowers the risk of developing Alzheimer's disease or other forms of dementia, according to the most comprehensive study to examine the benefits of challenging intellectual activity among the elderly.
Seniors who regularly engaged in pastimes that stretched their minds -- sorry, watching TV doesn't count -- lowered their risk of developing Alzheimer's disease and other dementias by as much as 75 percent, compared with those who didn't exercise their minds, researchers said yesterday.
The report bolsters a growing body of evidence that exercising the mind through board games, social activities and education offers powerful protection against mental deterioration and disease.
"I see a lot of elderly patients -- a lot come with memory complaints," said Joe Verghese, a neurologist at the Albert Einstein College of Medicine in the Bronx, who led the study team. "They have so-called senior moments -- they go in a room and forget why they are there. One thing I advise is for them to increase their participation in cognitively stimulating activities."
Some mental activity appears to be better than none, said Verghese. And the more hours seniors spent doing challenging tasks, the more protection they gained against brain decline. The day may not be far off, he said, when doctors recommend a game of chess and the daily crossword along with physical exercise and a healthy diet.
The benefits of such activities -- widely available and inexpensive -- appear to benefit those at all levels of education and IQ.
the finding comes as researchers race to find ways to slow or prevent disorders such as Alzheimer's disease, which afflicts 4 million Americans. As the large number of people in the baby boom generation age, dementia-related disease is expected to rise, and reducing its toll could have enormous ramifications.
Equally intriguing from a scientific standpoint is the idea that mental activity such as playing bridge can alter the molecular march of a neurological process.
"How can the molecular determinism of Alzheimer's disease be trumped by elderly people's card-playing?" asked Joseph Coyle, a professor of psychiatry and neuroscience at Harvard Medical School, in an analysis of Verghese's study. Both papers are being published today in the New England Journal of Medicine.
"The apparent conflict is between biology and psychology," Coyle said in an interview. But neuroscientists are finding that in many ways the brain is "plastic" -- thoughts and experiences change neural structure and chemistry.
"Using the mind actually causes rewiring of the brain, sprouting new synapses -- it may even cause the generation of new neurons," Coyle said. "So psychology trumps biology."
The new study tracked 469 people over age 75, starting in 1980. The researchers measured how often they participated in leisure activities such as reading, walking, dancing and board games. As people aged, researchers tracked how many people developed dementia.
Verghese's team also solved a chicken-and-egg problem that dogged previous research: Do mental activities really prevent dementia, or does dementia cause people to lose interest in mental activities? By screening out anyone who might have had dementia at the outset from their analysis, the researchers showed that leisure activities influenced dementia in their study, and not the other way around.
Those who played board games had a 74 percent lower risk and those who played an instrument had a 69 percent lower risk. Doing crossword puzzles cut the risk by 38 percent.
Purely physical activities failed to lower the risk, said Verghese, except for dancing, which lowered the risk by a dramatic 76 percent. Of all the physical activities, dancing involved the most mental effort, the researchers noted. A previous study found benefits for gardening, which also involves both mental and physical effort.
Andrea Farbman, executive director of the American Music Therapy Association, noted that music therapy is being widely used in Alzheimer's disease care.
"These are people who would not know what day it is, what their name is or where they are, but they can recall the songs, the chord and music," she said.
Lon S. Schneider, professor of psychiatry, neurology and gerontology at the University of Southern California, said that while final proof of the benefits of mental activity would require a study that compared people who systematically increased mental activity against a group that did not, the current results were promising.
"Use it or lose it -- exercise your mind," he said. Schneider said that because participants in Verghese's study had probably been involved in leisure activities their whole lives, it would be unwise to advise 80-year-olds who had never been mentally active to solve a crossword puzzle every day.
Rather, he said, people should find ways to stretch their minds doing things they already enjoy: "If you are interested in sports, learn the box scores," he said. "Learning the statistics is learning and memory."

(c) 2003 The Washington Post Company

Journal Watch (May 27, 2003)
47.Serum Cholesterol Is Not Related to Risk for Alzheimer's Disease

Physician-authored summaries and commentary from the publishers of the New England Journal of Medicine

Posted 06/24/2003

Summary
The apolipoprotein E (APOE)4 allele is a well-established risk factor for Alzheimer's disease (AD). However, the underlying pathophysiologic connection is unclear, despite observed associations between APOE4 and increased serum cholesterol, between lipoprotein(a) and AD, between cardiovascular risk factors and dementia, and between use of statins and lower risk for AD.

Researchers followed a cohort of 1026 participants in the Framingham study who were free of vascular disease and dementia in 1988-1989, had undergone APOE genotyping, and had serial cholesterol determined biennially from 1950 through 2000. AD developed in 77 subjects from 1992 through 2000. Risk for developing AD was not associated with any measured serum cholesterol levels, including lifetime mean total cholesterol level (from baseline in 1948 through 1978), total cholesterol level in 1988, HDL cholesterol level in 1988, or change in cholesterol level between 1978 and 1988. These results were not altered by adjustment for potential confounders such as age, sex, APOE genotype, coronary artery disease, lipid-lowering therapy, and body-mass index.

Comment
The long-term follow-up on this case-control cohort gives considerable credence to the investigators' conclusion: No association exists between serum cholesterol and risk for developing AD. The authors also conclude that the association between statin use and decreased risk for AD probably is not due to reductions in serum cholesterol.

-- Thomas L. Schwenk, MD

48.Small Study Suggests Insulin-Alzheimer's Link

Mon June 23, 2003(Reuters)
By Natalie Engler
NEW YORK (Reuters Health) - New research suggests that high levels of insulin may boost production of brain proteins that are linked to Alzheimer's disease.
In a small speculative study, investigators found that giving older people very high doses of insulin increased the amount of a starchy protein that forms plaques in the brains of people with Alzheimer's disease. The relationship between insulin and levels of the protein was most pronounced in the oldest participants.
The results suggest that treatments that lower insulin levels or improve its effectiveness may help delay or prevent Alzheimer's disease, Dr. Suzanne Craft of the Veterans Affairs Puget Sound Health Care System in Seattle said in an interview.
The results also underscore the importance of treating and preventing diabetes, making it increasingly clear that "high insulin levels are bad for your brain, as well as for your body," she told Reuters Health.
People with type 2 diabetes often lose their sensitivity to insulin, and have elevated blood levels of the blood-sugar-regulating hormone. Type 2 diabetes, the most common form of the disease, typically develops later in life and is often related to lifestyle and obesity.
Craft and her colleagues report their findings in the June issue of the journal Neurology.
Because many scientists suspect that the protein, called beta-amyloid, initiates a process that results in Alzheimer's disease, much research has focused on developing drugs that decrease its production or stimulate its breakdown or removal.
This new study is the first to suggest that beta-amyloid levels can be altered by giving people insulin, said Craft, who is also a professor of psychiatry at the University of Washington School of Medicine.
To investigate insulin's effect on the abnormal proteins, Craft and her colleagues studied 16 healthy adults aged 55 to 81. Half of the volunteers received an intravenous dose of insulin (mixed with dextrose to maintain blood sugar levels) followed by a placebo. The other half of the participants received the placebo first.
When the researchers compared the levels of beta-amyloid in the fluid that cushions the brain and spinal cord, they found that insulin raised the levels of a type of beta-amyloid called AB42. The increase was most pronounced in participants age 70 and over.
AB42 is the major form of beta-amyloid deposited in plaques.
In keeping with previous studies, the researchers also found that insulin aided recall, but only in the younger participants. People who had the greatest jump in beta-amyloid levels fared the worst on memory tests.
The reasons for the age discrepancy in memory are unclear, but the authors speculate that younger people may more effectively clear AB42 from their brains than older folks.
"Although we need to confirm our results in a larger group of patients, taken together, they suggest that problems with insulin metabolism may affect beta-amyloid levels and memory, and in doing so contribute to the development of Alzheimer's disease for some adults," said Craft.
She added that "the results are also consistent with reports that conditions associated with chronic high insulin levels, such as (high blood pressure) or diabetes, increase the risk of developing Alzheimer's disease."
But whether insulin increases the release of beta-amyloid from cells or blocks its clearance remains unknown, Dr. Douglas Galasko, of the VA Medical Center and the University of California in San Diego points out in an editorial accompanying the report.
In an interview, he also noted that the dose of insulin given to the study participants was much higher than the amount diabetics typically receive or the body produces naturally.
"We don't know if lower levels of insulin would also lead to changes in AB42 levels," he told Reuters Health.
However, he notes in his editorial that the small study "will undoubtedly stimulate further research relating insulin and Alzheimer's disease," including investigation of an enzyme that breaks down both insulin and beta-amyloid.

SOURCE: Neurology 2003;60:1886-1887,1899-1903.

49.Adding Fish to Diet May Reduce Risk of Alzheimer's
Monday, July 21, 2003

CHICAGO - Older people who eat fish at least once a week may cut their risk of Alzheimer's (search) by more than half, a study suggests.

The study adds to the evidence that diet may affect a person's chances of developing the mind-robbing disease that affects 4 million Americans.
Researchers found that people 65 and older who had fish once a week had a 60 percent lower risk of Alzheimer's than those who never or rarely ate fish. The meals included tuna sandwiches, fishsticks and shellfish; the amounts eaten were not specified.
"This is very promising, but it's very early and really we need to have a lot more studies," said lead researcher Dr. Martha Clare Morris of Chicago's Rush-Presbyterian-St. Luke's Medical Center (search).
The study involved 815 Chicago residents 65 and older. Follow-up tests nearly four years later found that 131 participants had developed Alzheimer's.
The researchers found an association between eating fish and a reduced risk of Alzheimer's even after adjusting for age, sex, ethnicity and risk factors like heart disease.
The study was published Monday in the Archives of Neurology (search). It was funded by the National Institutes of Health (search).
If the finding holds up, it could provide a simple way for people to reduce their risk of Alzheimer's, said Neil Buckholtz, chief of the dementia division at the National Institute on Aging (search).
Fish is rich in an omega-3 fatty acid (search) that is believed to be important for brain development, Morris said. Studies have shown that animals fed the fatty acids had better learning abilities and memory, she said.
She said some participants in the latest study also saw a decreased risk of Alzheimer's from eating omega-3 fatty acids found in vegetables and nuts.
The same researchers found in an earlier study that people who have diets heavy in saturated fats run double the risk of getting Alzheimer's.
Dr. Rachelle Doody, professor of neurology at Baylor College of Medicine in Houston, questioned the new study's conclusion and warned, "Articles like this raise expectations and confuse people."
Doody said the researchers "can show an association, but they can't show cause and effect" between fish and Alzheimer's.
She said it is not known whether those people who had a reduced risk had eaten fish most of their lives, and whether other dietary habits had an influence. Also, those studied were asked to recall their diets nearly two years later on average, Doody said.
Bill Thies, vice president of medical and scientific affairs at the Alzheimer's Association, called the study "an interesting suggestion."
"It's not definitive proof. It points in the direction of benefits," he said.

August 18, 2003
50.New Alzheimer Projections Add Urgency to Search for Prevention, Cure
Investment in Research Critical to Heading off Collapse of Health Care System

Chicago, IL/Washington, DC - An expected Alzheimer's epidemic will be far worse than previously thought, according to a new study published in the current issue of Archives of Neurology. The study, "Alzheimer's Disease in the U.S. Population," predicts the prevalence of Alzheimer's disease will increase 27% by 2020, an astonishing 70% by 2030, and nearly 300% by 2050, unless science finds a way to slow the progression of the disease or prevent it.

According to the study's authors, current and future estimates of Alzheimer's disease are essential for public health planning. But because Alzheimer's can progress slowly and is often not diagnosed, and because there is no requirement that the disease be reported, it has been difficult to gauge the scope of the problem.

According to Sheldon Goldberg, president and CEO of the Alzheimer's Association, "If left unchecked, it is no exaggeration to say that Alzheimer's disease will destroy the health care system and bankrupt Medicare and Medicaid."

Funded by the Alzheimer's Association and the National Institute on Aging, and conducted by researchers from the Rush Institute on Healthy Aging, the Rush Alzheimer's Disease Center, Rush-Presbyterian-St. Luke's Medical Center, and the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, the study evaluated the incidence of Alzheimer's in a biracial urban community, and applied the findings to U.S. Census data and National Center for Health Statistics mortality data to estimate prevalence in the U.S. population.

The researchers, led by Denis Evans, M.D., estimate that currently some 4.5 million Americans have Alzheimer's. Using low, middle and high U.S. Census projections, the researchers calculate Alzheimer's prevalence over the next five decades. The study predicts that by mid-century, between 11.2 and 16 million Americans will have Alzheimer's, with the medium number of cases expected to reach 13.2 million. The new numbers represent a significant increase over a 1990 study by the same researchers that estimated 7.5 to 14.3 million cases, with a medium range of 10.2 million, by 2050.

“Our choice is clearer than ever," said Goldberg. "Either increase funding for research to fend off this looming public health disaster, or sit back and wait for it to overwhelm the health care system."

The study suggests the increases in the prevalence of Alzheimer's disease are a result of the rapid growth of the oldest age group - 85 years and over - and of a decline in the death rate among persons over age 65 to about half the current rate by 2050. According to the study, by 2030 nearly half the individuals with Alzheimer's will be 85 years and older.

“Age is the single greatest risk for the disease," said Goldberg. "This study represents a significant step forward in confirming what we're up against. If we don't find answers soon, it will be devastating on multiple fronts."

Numerous economic studies have shown that Alzheimer's disease costs American business $61 billion annually, and by 2010, Medicare spending on Alzheimer's will rise to $49.3 billion (a 54% increase over costs for 2000) and Medicaid costs will rise to $33 billion (an 80% increase).

According to Goldberg, the solution to Alzheimer's lies in finding a way to prevent the disease or delay its onset so that millions of people now at risk never suffer its disabling effects. "The only way to do that is through investment in highly focused basic science research and clinical trials that will bring scientific discoveries out of the laboratory and into the hands of the people who will benefit from them," Goldberg said.

The Alzheimer's Association has been working with Congressional leaders to increase federal funding for Alzheimer research - from the estimated $640 million the National Institutes of Health will spend in 2003, to $1 billion annually. However, in the current budget climate, these requests have not seen significant movement. The Senate Appropriations Committee has proposed a 3.7% increase next year over current funding. Next month when the Senate returns, Senator Arlen Specter (R-Pa) and Senator Tom Harkin (D-IA), plan to offer an amendment that would provide a 9.2% increase. According to scientists, without these additional funds, the pace of Alzheimer research will slow dramatically.

After the NIH, the Alzheimer's Association is the leading source of Alzheimer research funding in the U.S.

The study concludes, "The large public health challenge is to make these projections obsolete and irrelevant by discovering routes to the prevention of the illness through better understanding of its underlying biology and by discovery of modifiable risk factors."

TheWBALChannel.com November 26, 2003
51.NIH Establishes Toll-Free Alzheimer's Hotline　Hotline Provides Information About Memory Problems

Federal health officials offer free help to those who notice changes in older family members.

The National Institutes of Health recently established a toll-free telephone program for caregivers, friends and family members who worry that a loved one may be suffering from Alzheimer's disease.
Studies show that family members are often the first to notice early changes, but in many cases, aren't sure if they are true symptoms of a memory problem.
"We know that half of persons with Alzheimer's disease go unrecognized. This is primarily because the early symptoms are subtle, are often dismissed by family and friends and often times unrecognized by medical practitioners," said Dr. Mark Sager, who is with the Wisconsin Alzheimer's Institute.
The hotline, called the Alzheimer's Early Recognition Telephone System (ALERTS), is anonymous and confidential. It offers a brief screening test that can tell someone who is worried about memory problems whether they need to get help.
The toll-free number is (800) 289-4974.

reference:Alzheimer's Early Recognition Telephone System (ALERTS) 1-800-289-4974
Approximately 4 million Americans have Alzheimer's Disease and more people are diagnosed with the disease every day. Although there is no cure for Alzheimer's disease at this time, there are medications available that can help people stay alert and active longer than they would without treatment. Unfortunately, many people overlook memory loss because they mistakenly believe that it is a normal part of aging. When memory loss goes undetected, people lose the opportunity for early treatment of the disease as well as the opportunity to participate in planning for their futures.
The Alzheimer's Early Recognition Telephone System (ALERTS) provides Wisconsin residents free, anonymous access to information about Alzheimer's Disease and other dementias, dementia screening tools, and contact information for local dementia diagnostic and support resources.
Call ALERTS to find the answers to these and many other questions:
When is forgetfulness normal?
What is dementia?
What is Alzheimer's disease?
How is dementia treated?
Should I see a doctor about my memory concerns?
Strategies for planning for the future
How do I take care of someone with dementia?
Where can I get the help I need? What resources are available in my community?
For those concerned about their own memory or those recently diagnosed with dementia...
ALERTS allows you to anonymously take a screening exam that will let you know if you should visit a doctor about your memory concerns. ALERTS provides up-to-date medical information about dementia and Alzheimer's disease, current treatment options, referrals to local diagnostic and support resources. Strategies for disclosing a diagnosis, discussing prognosis with your physician and family, and planning for the future are also included.
For those concerned about someone they love...
ALERTS offers a screening tool to assess whether the person you are concerned about should be evaluated by a physician, current medical information about dementia, and symptoms and warning signs of different types of dementia. ALERTS can also help you to prepare for a memory diagnostic exam, including ideas on how to get someone resistant in for a memory assessment. Information is also provided about what to expect and how to cope after a diagnosis is made. ALERTS can also refer you to organizations in your area that can offer more information, support and assistance.
For those caring for someone with dementia...
ALERTS offers information on care strategies, tips on dealing with some of the most common challenges, what to expect as the disease progresses and the importance of self care. Separate assessment tools allows caregivers to monitor their stress and levels of depression and provides links to support and assistance available in their local communities.
ALERTS - 1-800-289-4974

Tuesday, December 16, 2003 CNN health
52.Alzheimer's may start decades before signs appear

WASHINGTON (AP) -- A study of young adults who have a gene mutation linked to Alzheimer's suggests the brain-destroying disease starts decades before symptoms appear, indicating that someday it might be possible to begin prevention therapies at an early age.

A team led by researchers at the Banner Good Samaritan Medical Center in Phoenix scanned the brains of 12 young patients who have a mutation of the APOE gene associated with a high risk of Alzheimer's disease. They found that the young patients shared some of the same metabolic changes seen in patients with advanced and mild cases of the disease.
"People with this susceptibility gene have reduced brain activity in each of the brain regions that are progressively affected later in life" among Alzheimer's patients, said Dr. Eric M. Reiman, chief of the Positron Emission Tomography Center at Banner and first author of the study.
The study appears this week in the Proceedings of the National Academy of Sciences.
Reiman said researchers have yet to prove a link between the metabolic changes and the development of the disease, but the finding "suggests that there are brain changes many years before the possible onset of memory and thinking problems.
"We believe these brain changes provide a foothold for the development of some of the microscopic and metabolic abnormality that we see in patients later in life," he said.
Bill Thies, vice president of Medical and Scientific Affairs for the Alzheimer's Association, said the Reiman study is part of an ongoing effort by many researchers to find a way to identify at an early age who will later develop the memory loss and thinking problems of Alzheimer's disease.
There is no proven preventive therapy now for Alzheimer's, but Thies said that when the therapy is found, doctors will need to have tests that can identify patients.
Thies said studies of the way the brain processes glucose in patients with Alzheimer's is considered quite promising in the search for early clinical evidence of the disease.
"The best that can be said is that there is a correlation between glucose utilization and (Alzheimer's) pathology," said Thies. "Whether it is causative, we can't say."
Alzheimer's is a progressive and fatal brain disease that slowly wipes out memory and, eventually, all cognitive function. The disease is marked by deposits of plaques and tangles in key parts of the brain, causing the progressive and wholesale death of neurons. The precise cause is unknown and there is no cure, although some drugs can modify the course of the disease in some patients.
In the study, Reiman and his team conducted brain scans on 12 patients with a gene mutation linked to Alzheimer's. They compared these scans with those from 15 patients who were not carriers of the gene. All the study subjects were between 20 and 39, an age which is usually decades before the onset of Alzheimer's symptoms.
Reiman said they found that the gene carriers had an abnormally low level of brain glucose metabolism, when compared to the non-carriers. He said the low level of metabolism occurred in the same sections of the brain that other studies have shown are most dramatically affected in Alzheimer's patients. Earlier studies have found low levels of glucose metabolism in the brains of patients with mild and severe Alzheimer's.
"This study suggests that it may be possible to target brain changes and prevent Alzheimer's by intervening at a young time when that intervention will be particularly effective," said Reiman. "The thinking is that the earlier you can detect brain changes, the earlier you might be able to intervene with a prevention therapy."

December 16, 2003
CANADIAN COLLOQUIUM ON DEMENTIA

53.AD pathology doesn't always predict the disease
Even with high lesions and plaques, some never display AD symptomology

By Susannah Benady

MONTREAL - The quest to unravel the complexities of how Alzheimer's develops has revealed some individuals are blessed with the ability to override the illness, despite having the brain abnormalities usually associated with the disease.
So while technically having the same physiologic changes as Alzheimer's patients, they can nonetheless continue to function at a high level, according to findings from the Nun Study, a longitudinal study of aging and Alzheimer's disease.
Those who enjoy a high degree of "brain reserve" appear to be able to withstand the ravages of senile plaques, neurofibrillary tangles and genetic susceptibilities to the disease without expressing the clinical symptoms of Alzheimer's, said co-researcher Dr. Suzanne Tyas (PhD), in a presentation here recently at the second Canadian Colloquium on Dementia.

Serum folate levels
One factor that predisposes a person to good brain reserve appears to be high serum folate levels, one of 18 nutritional markers the researchers tested for correlation with the disease.
Larger brain size and more education can also provide this extra reserve, the researchers found.
"A number of subjects in our study were found on postmortem to have a high degree of senile plaques, neurofibrillary tangles and lesions," said Dr. Tyas, assistant professor of gerontology at the University of Kentucky, where the study is being conducted.
"And yet they showed no clinical signs of Alzheimer's while alive, and continued to function at a high cognitive level."
The Nun Study, begun in 1992, has followed 678 Roman Catholic sisters, initially 75 to 102 years of age, who are evaluated yearly and who have agreed to brain donation at the time of death.
Supported by the National Institute on Aging, it is one of the first large autopsy studies to include normal as well as demented participants.
The study has shown while genes (particularly apolipoprotein E4), early environmental influences and neuropathology are all important contributors to the disease, an individual can suffer in all three areas and yet live and function as normal-or better.
One of the nuns, Sister Bernadette, was found at postmortem to be on the 80 to 95 percentile for neurofibrillary tangles and senile plaques, and also had a high-risk genetic profile. She nonetheless displayed "stellar" cognitive performance on annual tests right up until she died.
"Sister Bernadette was at the very highest levels (of plaques and tangles) with an enormous neuropathologic load," said Dr. Tyas, who works at the university's school of public health.
"She was Braak stage 6-the highest-based on the number of pathologic lesions, their distribution and how far they have progressed.
"In addition, she had the highest genetic risk of apolipo-
protein E. So we were expecting a particular clinical profile."
However, when the researchers matched the brain to the results of the annual tests completed by every participant in the study, they found the opposite of what they had expected.
"Sister Bernadette's last clinical exam showed her as highly accurate on time assessments-very strong cognitive performance throughout her life, certainly no hint of dementia.
Cognitive improvement
"Her cognitive measures not only showed stability, some even showed improvement. There was certainly no clinical picture of dementia."
The finding was enough of a surprise that it raised the question of whether there had been an administrative slip-up along the way.
"We had to double-check that we hadn't made a mistake matching the brain with the cognitive tests," said Dr. Tyas.
But while unusual, the case of Bernadette was not unique. Up to 30% of participants who were found to have severe neuropathology post mortem did not experience dementia while they were living.
The remaining 70% did suffer from dementia and generally speaking, the study found the percentage of subjects who had dementia increased strongly depending on the severity of Alzheimer's pathology in the brain.
Even mild neuropathology was enough to cause obvious dementia in some individuals.
"After death, the neuropathologist counts and stages the lesions
. . . and found of those who had the mild stage of the disease, 21% were clinically diagnosed while alive. So even mild neuropathology resulted in dementia."
But, clearly, pathology, while it has an impact, is not the only story, said Dr. Tyas. Neither, the study has shown, are vulnerable genes.
Genetics
"The percentage of participants (who) had Alzheimer's was related to the number of apolipoprotein E4 alleles.
"But genetic risk factors are not a complete explanation either, because fewer than half of the (participants) with two apolipoprotein E4 alleles had Alzheimer's."
The researchers have concluded what protected Bernadette and her non-suffering counterparts was the cognitive reserve afforded by the absence of physical brain shrinkage.
"Sister Bernadette did not experience atrophy, or shrinkage of the brain, even though she had a lot of neuropathology," said Dr. Tyas.
"We believe this buffered the pathologic impacts of the plaques and tangles."
The Nun Study researchers have also found that a larger brain size and more years of schooling can also provide this extra reserve.
Subjects who completed 16 or more years of formal education or whose head circumference was in the upper two-thirds, denoting a larger brain, were four times less likely to be demented than those with both smaller head circumferences and less education.
Since no association between education or head circumference and severe brain abnormalities was found, having higher education or a larger brain does not decrease the chances of Alzheimer's brain abnormalities, but rather allows the brain to function at a higher level despite these abnormalities, said the researchers.

54.Drug Shows Promise in Targeting Alzheimer's Root
Mon December 15, 2003 Reuters

NEW YORK (Reuters) - A preliminary study of an antibiotic drug showed promise in reducing the plaque believed to be the root cause of Alzheimer's disease and could lead to the development of a new treatments, researchers reported on Monday.
A clinical trial of the drug, clioquinol, led by researchers at the University of Melbourne in Australia, appeared to improve cognitive function in patients with Alzheimer's by lowering levels of a protein known as beta-amyloid that is thought to be implicated in the build-up of plaque.
Most Alzheimer's researchers believe that the cause of the disease is formation of plaque in the brain. But that has yet to be definitively proved.
"The main importance of studies like this is to attempt to prove the principle that amyloid-lowering agents can stabilize or possibly even reverse cognitive decline in Alzheimer's," said William Thies, vice president of medical and scientific affairs at the Alzheimer's Association.
In a pilot trial of 36 patients with moderately severe Alzheimer's disease who received the drug clioquinol, researchers found that beta-amyloid levels declined in the clioquinol group and increased in the placebo group. Patients taking clioquinol also performed better on a test of cognitive ability.
The research, which appeared in the December issue of The Archives of Neurology, suggests that clioquinol works by inhibiting zinc and copper ions from binding to beta-amyloid, helping to dissolve the protein and preventing it from accumulating.
"The findings support a proof of concept in humans that a drug targeting metal/beta-amyloid interactions can have a significant effect on beta-amyloid metabolism, and through this, a beneficial modification on the progression of Alzheimer's disease," the researchers said.
Still, Thies said that while the trial is promising it is too small to draw definitive conclusions.
"The sample size is very, very small and the effect is not dramatic."
Now the researchers are applying to the U.S. Food and Drug Administration to conduct a bigger trial, of 80 people. But there are substantial safety concerns with clioquinol. The drug, introduced more than 30 years ago as an antibiotic, was withdrawn after several thousand people, mainly Japanese, developed vitamin B deficiencies that in some cases led to blindness.
The researchers said they are supplementing their patients with vitamin B and so far have seen no such symptoms. Even so, the company that holds the rights to the drug, Prana Biotechnology Ltd. of Australia, no longer plans to plow money into the drug. It will concentrate on developing derivatives instead.
Researchers plan to continue to study clioquinol, however, in conjunction with Sam Gandy, director of the Farber Institute for Neurosciences of Thomas Jefferson University in Philadelphia.
"I think the general approach is extremely exciting," said Gandy. "At this point in the field of Alzheimer's the most important question to answer is whether plaque is causative of the disease or merely a bystander."
Several other companies, including Neurochem Inc., are developing drugs aimed at inhibiting the development of amyloid protein or dissolving it once it is formed. There is some evidence that dissolving plaque reduces symptoms of the disease, which range from memory loss to dementia.
"Any study that establishes that an anti-amyloid drug could stabilize or reverse cognitive decline would be a landmark study," Gandy said.

55.Now, Reduce Your Risk of Alzheimer's
Intriguing new studies say the same measures that help your heart could also help prevent dementia
Newsweek Jan. 19 issue

Michael Lewis for Newsweek
Scientist Martha Clare Morris' (center) study suggests seniors who eat fish have a lower risk of Alzheimer's
By Anne Underwood

Just days into 2004, are you already struggling with those New Year's resolutions to eat right, exercise and shed excess pounds? Here's added incentive to stick with the program. It turns out that the healthy measures most of us vow to take every New Year's could not only make us look better in bathing suits but also lower our risk of Alzheimer's disease.

For generations, Alzheimer's has seemed as unpredictable as a game of chance-either you win or lose at dementia roulette. But that picture is starting to change. Scientists have long known that proper diet, exercise and weight control can help lower the risk of heart disease, strokes and vascular dementia. Now they're recognizing that the same healthy-lifestyle factors may also lower the risk of Alzheimer's. In short, what's good for the heart is good for the brain. Next month the Alzheimer's Association, a nonprofit group in Chicago that supports research and services for families, will begin rolling out a campaign to raise awareness of the new findings. "Over the last three years, the single most significant trend in research is the evidence that risk factors for heart disease track with those for Alzheimer's," says Bill Thies, vice president of medical and scientific affairs.

The vascular hypothesis, as the idea has come to be known, got its tentative start in the 1980s at the medical examiner's office in Lexington, Ky. Neuropathologist Larry Sparks, who was then the chief bio-medical consultant, was studying the brains of people who had died in a variety of accidents. None of the victims had overt signs of dementia. But Sparks noticed that many of their brains bore the same telltale amyloid plaques and neurofibrillary tangles that characterize the brains of Alzheimer's patients. As the number of cases grew, he noticed something else. Plaques and tangles were three times more common in the brains of people with heart disease. "That suggested that if they were resilient enough not to succumb to heart trouble in their 60s, they might be star-ing down the loaded barrel of dementia in their 80s," says Sparks, now with the Sun Health Research Institute in Arizona. The scientific community was skeptical.

Then results started coming in from long-term epidemiological studies. In 1996 Dr. Ingmar Skoog, a psychiatrist at Goteborg University in Sweden, published a study in The Lancet showing a correlation between high blood pressure at the age of 70 and a tendency to develop Alzheimer's 15 years later. Was hypertension years earlier setting people up for Alzheimer's in their old age?

Other studies suggested it was. In 2000 the Honolulu-Asia Aging Study reported that middle-aged Japanese-American men with diastolic blood pressure over 90 (the second of the two blood-pressure readings is diastolic) ran five times greater risk of dementia 20 to 25 years later than those with diastolic pressure in the 80-to-89 range. If the men treated their high blood pressure, however, risk of later Alzheimer's fell. The Honolulu findings were particularly powerful because the researchers were able to examine the brains of participants at death. "The higher their midlife blood pressure, the more plaques and tangles they had on autopsy," says Lenore Launer, chief of neuroepidemiology at the National Institute on Aging and one of the investigators.

In the last three years, still more cardiac risk factors have been implicated in Alzheimer's disease-obesity, smoking, atherosclerosis, high cholesterol and excessive levels of a substance in the blood called homocysteine. Moderate smoking, for example, doubled or tripled Alzheimer's risk in two studies. (Heavy smokers, don't think this lets you off the hook. Scientists say the only reason a two-pack-a-day habit doesn't turn up as a risk factor is that heart disease kills so many people before they are old enough to develop Alzheimer's.) And as America's girth expands, keep in mind that obesity poses a risk, too. In the Goteborg study in Sweden, every one-point increase in body-mass index at the age of 70 increased the risk of Alzheimer's 15 years later by 36 percent. Diabetes, which is also associated with excess weight, doubled the risk of Alzheimer's in two other large surveys.

Want to lower your chances of dementia? A heart-healthy diet is a good place to start. Last summer Martha Clare Morris of the Rush Institute for Healthy Aging in Chicago published an epidemiological study showing that senior citizens who ate fish at least once a week reduced their risk of Alzheimer's four years later by 60 percent. It's way too early to say why, but Morris noted a particular correlation between intake of DHA-one of the omega-3 fatty acids in fish-and reductions in Alzheimer's. "DHA is the primary lipid in the brain," she noted. In other surveys, she's found that those who eat the greatest quantities of foods containing vitamin E-such as vegetable oils, wheat germ, whole grains, sunflower seeds and collard greens-reduce their risk as much as 70 percent. On the opposite side of the ledger, saturated fat and trans fats, long a target of the American Heart Association, appear to increase the incidence of Alzheimer's. Healthy Heart, Healthy Brain

Changing your lifestyle isn't foolproof protection against Alzheimer's disease. But the same measures that help the heart appear to help the brain. Here are some of the steps you can take to improve your odds of staying sharp well into old age.

MEASURES TO TAKE
Keep blood pressure in the normal range-below 120/80
Eat a heart-healthy diet, including fish and foods rich in vitamin E
Control cholesterol levels
THINGS TO AVOID
Smoking
Foods high in saturated fats and trans fats (partially hydrogenated vegetable oils)
Excess weight, overeating and a sedentary lifestyle

At this stage, none of these results are conclusive. The evidence comes mainly from epidemiological studies, which find associations but don't establish cause and effect. "A survey might find that people get less dementia if they wear Brooks Brothers shirts," jokes Dr. Bruce Yankner at Harvard. "But maybe the fact they wear button-down shirts is just an indicator that they are well to do and therefore take better care of their health." The vascular hypothesis won't be secure, he says, until research firmly links cardiovascular risk factors to mechanisms underlying the development of Alzheimer's. Such evidence is starting to emerge. For example, scientists have shown that high cholesterol in rabbits, mice and guinea pigs leads to increased formation of amyloid plaques in the animals' brains. But the evidence is still preliminary.

Even if all the research holds up, there are no guarantees that any individual will be able to avoid the devastating ill-ness. The rare early-onset Alzheimer's that strikes people in their 40s and 50s is heavily controlled by genetics. The more common late-onset form seems more amenable to reduction, but genes still play a role. In the end, however, it can't hurt to adopt more heart-healthy behaviors. With heart disease holding strong as the nation's No. 1 killer, you only stand to benefit by helping your heart. It's a no-brainer.

Source: Philadelphia College of Osteopathic Medicine Released: Tue 09-Mar-2004, 16:00 ET

Printer-friendly Version

56.Common Bacteria Linked to Alzheimer's Disease
Libraries
Medical News Keywords
ALZHEIMER'S DISEASE, CHLAMYDIA PNEUMONIAE, AMYLOID PLAQUES
Contact Information

Available for logged-in reporters only
Description

Researchers have shown a link between Chlyamydia pneumoniae and the amyloid plaques found in the brains of people with sporadic, non-hereditary Alzheimer's Disease.

Newswise ? The paper "Chlamydia pneumoniae induces Alzheimer-like Amyloid Plaques in Brains of BALB/c Mice," to be published in the April issue of Neurolobiology of Aging shows a link between the bacteria Chlyamydia pneumoniae and the amyloid plaques found in the brains of people who have sporadic, non-hereditary Alzheimer's Disease.

Researchers at Philadelphia College of Osteopathic Medicine's Center for the Study of Chronic Diseases of Aging have been studying a link between this common respiratory bacteria and pathology consistent with Alzheimer's Disease for several years. This most recent work builds on their ground-breaking research published in Medical Microbiology and Immunology in 1998 that discovered Chlamydia pneumoniae in 90 percent of brains taken from individuals who had suffered from Alzheimer's Disease. Their new work shows that the bacteria, when sprayed into the noses of mice not predisposed to amyloid plaques, can cause progressive deposition of amyloid plaques, in essence creating a partial model of Alzheimer's Disease.

“We believe this could be a trigger mechanism for the pathology in Alzheimer's Disease," says lead researcher Brian Balin, Ph.D. "People have been suspecting this for decades but could not find anything. It is very difficult to pinpoint an infectious cause for a progressive, chronic disease. We also believe that our isolation of Chlamydia pneumoniae from the human Alzheimer's Diseased brain and induction of pathology in normal mice is proof of principle that this can be a causative mechanism turning on pathology."

At one time, Alzheimer's was thought to be a hereditary disease. Research has shown that only two-to-five percent of Alzheimer's cases have a genetic tie. Fifty percent of people who reach age 85 will develop Alzheimer's

Balin is already looking further ahead. He wants to set up clinical trials in patients with late-onset AD to investigate the effect of typical antibiotics used for treating C. pneumoniae infections. But there is a lot of controversy now whether any existing antibiotics for C. pneumoniae can truly clear the organism from our bodies. "We try to intervene by using an antibiotic approach initially," says Balin. "I think it would offer hope to a patient that would have sporadic AD and would be diagnosed with having chlamydia infection as well. But in reality we are not sure whether the antibiotic approach will be sufficient to actually eradicate. Right now, we are thinking that combining antibiotics and anti-inflammatory drugs might be instrumental in treating AD, but obviously we do not have a final answer on that."

To access Neurobiology of Aging: http://www.sciencedirect.com/science/journal/01974580

[ 06 April 2004 Source:Inpharm.com

57.Links between obesity/diabetes & Alzheimer disease: Diet-induced insulin resistance shown to increase CNS beta-amyloid levels and worsens cognition in a model of Alzheimer disease

Daily Updates5th April: There is growing evidence of a link between type-2 diabetes/obesity and Alzheimer disease. Researchers now report that diet-induced insulin resistance increases beta amyloid generation, amyloid plaque burden in the brain and behavioural impairment in a model of Alzheimer disease.

The aging population will contribute to an expansion of the already $30 billion neurodegenerative market. The market for Alzheimer disease therapy is expected to grow from 16 million patients to 21 million by 2010 in the seven major pharmaceutical markets. Between 2005 and 2010, drugs for treating Alzheimer disease could achieve sales of well over $2 billion.

A second condition that has dramatically increased in incidence over the past decade is diabetes which, according to WHO currently affects some 130 million people world-wide, a figure that is predicted to increase to 300 million by 2025. The majority of patients suffer from type 2 diabetes. The global market for diabetes therapeutics reportedly topped $8.1 billion for the 12 months to September 2000, a 19% increase over the previous 12 months (for a full analysis of diabetes therapeutics and market opportunities click here).

An evolving concept is that diabetes is a risk factor for developing Alzheimer disease. Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes). Evidence is growing to link precursors of amyloid deposition in the brain and pancreas with the pathogenesis of Alzheimer disease and type 2 diabetes, respectively and a recent study has demonstrated that type 2 diabetes is twice as prevalent in Alzheimer disease versus non-Alzheimer disease controls.

The reason for diabetes being a risk fact for Alzheimer disease is unclear however increased beta-amyloid (Abeta) aggregation through inhibition of insulin-degrading enzyme is one hypothesis. Insulin-degrading enzyme (IDE) has been identified as a principal regulator of Abeta levels in neuronal and microglial cells and human genetic studies have implicated the Insulin-degrading enzyme region of chromosome 10 in both Alzheimer disease and type 2 diabetes. In a recent American Journal of Pathology article, Farris et al report that naturally occurring IDE missense mutations in a well-characterized rat model of type 2 diabetes mellitus result in decreased catalytic efficiency and a 15 to 30% deficit in the degradation of both insulin and Abeta. Endogenously secreted Abeta(40) and Abeta(42) are significantly elevated in primary neuronal cultures from animals with the IDE mutations although in these animals compensatory mechanisms appeared to prevent the in vivo build up of Abeta.

In their upcoming Faseb Journal article Ho et al report that diet-induced insulin resistance increases amyloidogenic beta-amyloid Abeta1-40 and Abeta1-42 peptide generation in the brain of Tg2576 mice, which model Alzheimer disease-like neuropathology. This corresponded with increased gamma-secretase activities and decreased IDE activities. Moreover, increased Abeta production also coincided with increased Alzheimer disease-type amyloid plaque burden in the brain and impaired performance in a spatial water maze task.

Further exploration of the apparent interrelationship of insulin resistance to brain amyloidosis revealed a functional decrease in insulin receptor-mediated signal transduction in the brain, and perhaps more importantly an increase in glycogen synthase kinase (GSK)-3alpha.

As in diabetes, GSK-3 is also elevated in Alzheimer disease brain. Furthermore, GSK-3 inhibitors prevent tau hyperphosphorylation, and also protect cultured neurons from cell death triggered by Abeta. GSK-3 inhibition improves glucose handling in various models of insulin-resistance/diabetes prompting the development of this therapeutic class for the treatment of metabolic disorders. This new data shows that in susceptible mice, insulin resistance can exaggerate characteristics of Alzheimer disease pathology and, furthermore, that increased GSK-3 activity may contribute to this phenomenon. Inhibitors of GSK-3 may therefore not only be of use to Alzheimer and metabolic disease per se but they may also break the link between the two conditions offering new treatment options to patients with metabolic disorders with or without Alzheimer disease (for a state of the art overview of GSK-3 click here).

57-1.New Research An Important New Step In Determining Whether Curry Can Protect Against Alzheimer's(April 11,2004)
Curcumin, which provides the yellow color in curry, may activate a key enzyme with antioxidative properties

Washington, DC -- A new study has found that curry, a common and popular cooking additive, could be an effective enhancer of an enzyme that protects the brain against oxidative conditions. This research is an important first step in determining whether curry could be preventive agent against acute neurodegenerative conditions, or reducing the progression of chronic and age associated neurodegenerative disorders, such as Alzheimer's disease.
Free Radicals and Neurodegenerative Disease
One of the most prominent current theories of aging is the "free radical theory." According to this theory, free radical molecules generated through mitochondrial metabolism can act as causative factor of abnormal function and cell death. Various toxins in the environment can injure mitochondrial enzymes, leading to increased generation of free radicals and oxidative stress, that over the life-span would eventually play a major role in aging. Free radical's oxidative damage to key intracellular targets such as DNA or proteins has been shown to be a major cause of the degenerative diseases related to aging such as cancer and Alzheimer's disease.
Luckily, mammalian cells have developed highly protective systems against including oxidative challenges over time. When properly activated, each one of these cell systems has the possibility to restore cellular homeostasis and resume the ability to fight off oxidation. Activation of antioxidant pathways is particularly important for tissue with relatively weak antioxidant defenses, such as the brain. In fact, increasing evidence points to the notion that reduced cellular expression and activity of antioxidant proteins and the consequent oxidative stress are fundamental causes for brain aging processes and neurodegenerative diseases.
HO-1 and Curcumin
There are a variety of genes encoding proteins that possess anti-oxidant properties. Of particular interest in the central nervous system (CNS) is the hemeoxygenase-1 (HO-1), which has been reported to operate as a fundamental defensive mechanism for neurons exposed to an oxidant challenge.
At the same time, a number of studies have supported the beneficial effects of some commonly used natural products in preventing various pathologic conditions. Spices and herbs often contain phenolic substances with potent antioxidative and chemopreventive properties. Among them is curcumin, a natural phenolic agent, extracted from the rhizome of Curcuma Longa, and the yellow pigment in curry, strongly induced HO-1 expression and activity in rat astrocytes.
In recent years, there has been an unprecedented interest in identifying new pharmacological strategies to increase defense mechanisms by activating multiple antioxidant defense genes, a process that has been referred to as programmed cell life. Previous studies have shown that induction of HO-1 can represent an efficient antioxidant system and a potential pharmacological target in a variety of oxidant- and inflammatory-mediated diseases, including brain aging and neurodegenerative disorders.
A New Study
A new study extends previous findings examining the neuroprotective effects of curcumin and its ability to induce HO-1 on cultured hippocampal neurons. This research effort investigated the effects of curcumin on the expression profiles of other genes involved in the cellular stress response. The study also explored subcellular localization of HO-1 protein in one of the large cells of nervous tissue after treatment with curcumin.
The investigators of a study entitled "Curcumin Cytoprotective Effect in Rat Astrocytes and Neurons is Mediated by Specific Induction of HO-1," will present their findings at the American Physiological Society's (APS) (www.the-aps.org) annual scientific conference, Experimental Biology 2003, being held April 17-21, 2004, at the Washington, D.C. Convention Center. The research team represents two countries. The Italian researchers are Giovanni Scapagnini from the Institute of Neurological Sciences, CNR, Catania, Claudia Colombrita and Vittorio Calabrese at the Dipartimento di Scienze Chimiche, Universita' di Catania, and Alessia Pascale, at the Department of Experimental and Applied Pharmacology, Universita' di Pavia, Pavia. In the United States, the researchers are Michael L. Schwartzman and Nader G. Abraham from the Department of Pharmacology, New York Medical College, Valhalla, NY.
Methodology
Rat type 1 astrocytes and rat hippocampal neurons were exposed to various concentrations of curcumin. After each treatment (six or 24 hours), cells were harvested for the determination of heme oxygenase activity and protein expression. The researchers also measured the expression of HO-1 and Phase II detoxification enzymes mRNAs by real time quantitative RT-PCR.
Neurons growing in 24 wells were also exposed to different concentrations of curcumin, and cell viability was determined at 24 hours. Other neurons were pretreated for 18 hours with curcumin 15?M or curcumin 15?M + zinc protoporphyrin IX (ZnPP IX) 10?M and then exposed for two hours to 50 mu/ml glucose-oxidase (GOX), before cell viability was determined.
Results
Treatment of astrocytes with curcumin increased expression of HO-1 protein at both cytoplasmatic and nuclear level, as shown by immunofluorescence analysis under laser-scanning confocal microscope. The researchers also found a significant expression of quinone reductase and glutathione S-transferase, two members of Phase II detoxification enzymes, in astrocytes exposed to 5-15 μM curcumin. With exploration of the effects of curcumin on HO-1 activity in cultured hippocampal neurons the researchers found elevated expression of HO-1 mRNA and protein. Higher concentrations of curcumin (50-100 μM) caused a substantial cytotoxic effect with no change in HO-1 protein expression. Interestingly, pre-incubation (18 h) with curcumin 15 μM resulted in an enhanced cellular resistance to GOX mediated oxidative damage; this cytoprotective effect was considerably attenuated by ZnPP IX, a specific inhibitor of heme oxygenase activity.
Conclusions
This study identifies a novel compound that could be used for therapeutic purposes as potent inducers of HO-1 for protecting brain cells against oxidative conditions. The researchers believe that additional in vitro and in vivo studies are necessary to determine whether curcumin can be used as preventive agent against acute neurodegenerative conditions that affect an increasingly aged population.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 11,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

58.Brown Rice May Prevent Alzheimer's Dementia: FANCL

Tokyo (JCNN 20/05/2004) - Japanese cosmetic manufacturer FANCL has announced that its research group has discovered the effectiveness of pre-germinated brown rice against Alzheimer's disease in collaboration with Meijo University Professor Makoto Ukai.

Based on their animal experiments, they have confirmed that there is a possibility that a continuous intake of brown rice effectively inhibits learning and memory deficits induced by beta-amyloid protein. Beta-amyloid protein is considered one of the factors to cause Alzheimer's dementia.
Detailed research results will be discussed in the forthcoming July 1 issue of "Biological & Pharmaceutical Bulletin," which is published by the Pharmaceutical Society of Japan.
An online version is already available under the title "Effect of pre-germinated brwon rice on beta-amyloid protein induced learning and memory deficits in mice" at https://denshi.pharm.or.jp/home/pubpharm/pubview.asp?p=b040013.
Currently, FANCL markets "hatsuga mai," a pre-germinated brow rice product, in Japan.
Copyright c 2001-2004 JCNN. All rights reserved. A division of Japan Corporate News Network KK.

Yahoo! News Fri, Jul 02, 2004

59.Big Blood Pressure Drop May Lead to Alzheimer's

Thu Jul 1, 7:02 PM ET Add Health - HealthDay to My Yahoo!

By Ed Edelson
HealthDay Reporter

THURSDAY, July 1 (HealthDayNews) -- A drastic drop in blood pressure may be a harbinger of Alzheimer's disease (news - web sites) and other forms of dementia in older people, new Swedish research finds.
The study, which followed nearly 1,000 Stockholm residents aged 75 or older, found that a 15-point drop in systolic blood pressure (the higher number in a blood pressure reading) was linked to a threefold increase in the risk of dementia. The report appears in the July 2 issue of Stroke.
Doctors consider a blood pressure reading of 120/80 as healthy.
This latest discovery adds complexity to the relationship between blood pressure and dementia. Several previous studies have shown high blood pressure in the midlife years is associated with an increased risk of dementia later in life.
The new finding is open to several explanations, said Dr. Laura Fratiglioni, a professor of geriatric epidemiology and leader of the group at the Karolinska Institute that did the study. One possibility is the same process that results in the brain damage of dementia also causes a drop in blood pressure.
"My personal hypothesis is that a decrease in blood pressure may facilitate a process that has already begun," Fratiglioni said, with lessened blood flow to the brain increasing the damage to brain cells that results in dementia.
There's also an outside chance that overzealous efforts by patients and their physicians to lower blood pressure might lead to brain damage, Fratiglioni said. "The message is not to treat high blood pressure but to treat it in a good way," she added, with careful monitoring of blood pressure levels through the years.
Each participant in the study had a blood pressure measurement and physical examination at the start, and again three and six years later. Blood pressure did drop slightly in participants who didn't develop dementia, but the drop was much sharper in those who developed the condition. And as blood pressure dropped, the severity of dementia increased.
Bill Thies, vice president for medical and scientific affairs at the Alzheimer's Association, said the only thing certain about the relationship between blood pressure and the loss of mental function seen in dementia is that "it is complex."
"It is possible that dementia causes a decrease in blood pressure," Thies said. "The same thing that causes damage to the brain may cause a decrease in blood pressure."
The relationship between high blood pressure earlier in life and the later development of dementia has been observed in several studies, he said. "The ultimate study would be to actually take a group of people and lower their systolic blood pressure in later life to see if it is beneficial or not," Thies said. "But that would be a difficult area to investigate."
Any link between high blood pressure and dementia later in life "is still obscure, and may be multifactorial," he said, but "there are increasing reasons to think that Alzheimer's disease and blood vessels and blood flow are related."
However, the fact that high blood pressure increases the risk of heart disease and stroke is unchallenged, Thies added, and doctors treating patients with Alzheimer's disease should take that into account.
"Because people have Alzheimer's disease doesn't mean you stop worrying about other medical problems," he said.

SCIENCE JOURNAL
By SHARON BEGLEY

60.Fevered Debate Over　Alzheimer's Origins　Causes Deep Divisions
August 6, 2004

Although the exchange did not quite descend to the level of name-calling, it was not what you usually hear at scientific conferences. Halfway into a debate on whether Alzheimer's disease is caused by the accumulation in the brain of sticky "plaques" made of a protein called beta-amyloid, as the leading theory holds, and whether therapies that target amyloid are the best bets, one scientist let loose.

"I think your treatment will kill people," said neuropathologist Mark Smith of Case Western Reserve University, Cleveland, referring to anti-amyloid therapies. To which neuroscientist Todd Golde of the Mayo Clinic, Jacksonville, Fla., responded, "Ethically, I would say you're not in the right place."

Behind the scenes at last month's 9th International Conference on Alzheimer's Disease (the amyloid debate was not part of the official program), you could almost trip on the ideological lines drawn in the sand.

Beliefs about what causes this merciless disease have taken on such a religious fervor that one group is called tauists, after a protein called tau that forms "neurofibrillary tangles" inside the neurons and, say these scientists, kills neurons responsible for memory and thought. Another is called baptists, after the beta-amyloid protein that forms plaques around brain neurons and, say its accusers, causes neuron-killing tau tangles or kills neurons directly, or both. Apostates think amyloid plaques sop up neurotoxic proteins along with poisonous metals such as zinc and copper, and that eliminating plaques could therefore harm patients. Hence Dr. Smith's accusation.

As I wrote1 last April, there are growing doubts that amyloid is guilty as charged. Autopsies of people with early-stage Alzheimer's show that the tangles form first, before plaques, in brain regions initially affected by the disease. "If you look at the evidence, it's the tangles that cause neuronal degeneration, and they come first, before the amyloid," says neurologist Patrick McGeer of the University of British Columbia, Vancouver, who was awarded one of the Alzheimer's Association's top scientific prizes at the meeting.

Another problem for the amyloid dogma is that "almost all aged brains have extensive amyloid deposition, even in people who die with no symptoms of Alzheimer's," says neurologist Peter Davies of the Albert Einstein College of Medicine in the Bronx. Worse, adds neurobiologist Nikolaos Robakis of Mount Sinai School of Medicine, New York City, autopsies of the brains of Alzheimer's victims show that "plaques don't correlate with neuronal death. The amyloid is here and the dead neurons are somewhere else."

The amyloid debate has taken on added urgency, for many Alzheimer's therapies now in the pipeline are predicated on the guilt of amyloid. A vaccine being developed by Elan Corp., Dublin, for instance, targets amyloid plaques; unfortunately, it also shrank the brains of many volunteers it was tested on. Drugs being developed by Eli Lilly & Co., Indianapolis, and Neurochem, Laval, Quebec, target amyloid, too.

"The question is, if we are successful in controlling amyloid, will we be successful in helping patients?," says Zaven Khachaturian, who ran the Alzheimer's program at the National Institute on Aging. "The field doesn't have a clue."

But it might soon. Scientists who believe that amyloid causes Alzheimer's have one indisputable fact on their side: Mutations in three genes which cause the familial, inherited form of the disease all pump up amyloid levels in the brain. Surely this proves amyloid's guilt?

In the huge diversity of views presented at the meeting -- there were 4,500 scientists and 2,000 presentations -- you could hear the beginnings of an answer. "There were some faint suggestions that these 'amyloid' mutations do something besides affect amyloid," says Dr. McGeer.

For instance, an Alzheimer's gene once thought to do nothing but make lots of amyloid turns out to have a second job, said Dr. Robakis: It also stabilizes proteins that help keep neurons alive. When this gene (it's called PS1) is mutated, it speeds the death of neurons by triggering those toxic tau tangles and by making neurons more likely to commit suicide. A second Alzheimer's gene, called APP and also thought to simply be a source of amyloid, also seems to moonlight. When mutated, it pushes neurons to change in ways that lead to suicide, finds Rachael Neve of Harvard Medical School, Boston.

In other words, mutations in "amyloid" genes wreak havoc in ways that don't involve amyloid.

Interestingly, suicidal neurons seem to release amyloid. Perhaps that has fooled scientists into concluding that the amyloid around dead neurons is the killer, when it is actually an innocent by-stander.

No existing drug stops, let alone reverses, the inexorable cognitive and memory decline of Alzheimer's. The one thing baptists, tauists and apostates agree on is that drugs that prevent the disease will not cure it, and drugs effective against early Alzheimer's won't be the same as those that work against late Alzheimer's. We'll need a whole armamentarium.

Will any of the treatments target amyloid? "If amyloid were the answer," says Dr. McGeer, "the disease would have been solved by now."

Copyright 2004 Dow Jones & Company, Inc. All Rights Reserved

61,Alzheimer's Risk Linked to Job Type In a New Study(August 10,2004)

By JENNIFER CORBETT DOOREN
DOW JONES NEWSWIRES
August 10, 2004; Page D4

People who hold mentally demanding jobs throughout their working years may be at lower risk for developing Alzheimer's disease, according to a new study.

The study, appearing in the Aug. 10 issue of Neurology, examines a potential link between Alzheimer's and the types of jobs people held from their 20s until age 60.

The study examined 122 people with the brain-wasting disease and 235 people without it. Everyone was age 60 or older. In general, the study found that people with Alzheimer's were more likely to have held less mentally demanding jobs than those without the disease. They were also more likely to have had physically demanding jobs.

However, the researchers said they aren't sure what the link is between Alzheimer's disease and occupations.

"It could be that the disease has a very early effect on the individual's capacity to pursue a mentally challenging occupation," said lead researcher Kathleen Smyth, an associate professor at Case Western Reserve University School of Medicine and at University Hospitals of Cleveland. "Or it could be that higher levels of mental demands result in increased brain-cell activity, which may help maintain a reserve of brain cells that resists the effects of Alzheimer's disease."

The researchers tallied information about the types of jobs, industry, the length of time in jobs and people's most important activities in their jobs. Then, using data developed by the U.S. Labor Department, Ms. Smyth and her colleagues looked at 44 measures of worker functions and traits to determine the mental demands of various jobs.

Those with managerial and professional jobs -- such as doctors, engineers, architects, stockbrokers and teachers -- fall into the most mentally demanding category.

Bank tellers, barbers, roofers and cooks rank in the middle on a continuum of high-to-low mentally demanding jobs.

When comparing the Alzheimer's group and the non-Alzheimer's group, researchers found that both groups held jobs with the same level of mental demand in their 20s. Then in their 30s, researchers started to find a divergence between the groups. Those without Alzheimer's typically moved to jobs with higher mental demands during their 40s and 50s, increasing the mental-demand level by about 33% across the decades.

The mental demands of occupations for those with Alzheimer's remained about the same in later decades. Ms. Symth said there is no way to quantify the risk of developing Alzheimer's with the types of jobs people hold.

One limitation of the study is the fact that it didn't control for socioeconomic status. People with higher socioeconomic status typically hold jobs with higher mental demands.

"Variations in income, access to health care and better nutrition...could be responsible in part for our findings," Ms. Smyth said.

About 4.5 million Americans currently suffer from Alzheimer's. By 2050, as the population ages and life expectancy grows, the number of Americans with the disease is expected to reach between 11.3 million to 16 million, according to the Alzheimer's Association.

Write to Jennifer Corbett Dooren at jennifer.corbett-dooren@dowjones.com1

URL for this article:
http://online.wsj.com/article/0,,SB109210158191487240,00.html

Hyperlinks in this Article:
(1) mailto:jennifer.corbett-dooren@dowjones.com

Copyright 2004 Dow Jones & Company, Inc. All Rights Reserved

This copy is for your personal, non-commercial use only. Distribution and use of this material are governed by our Subscriber Agreement and by copyright law. For non-personal use or to order multiple copies, please contact Dow Jones Reprints at 1-800-843-0008 or visit http://www.djreprints.com/.

NIH　News August 26, 2004

62.Study Shows Placing Relative with Dementia into Long-Term Care Facility Does Little to Ease the Emotional Burden of Caregivers

A new study shows that caregivers of dementia patients who must make the difficult decision to place their relatives into institutionalized care get no relief from depression and anxiety, and in fact suffer additional emotional trauma following their decision . The study, funded by the National Institute of Nursing Research and the National Institute on Aging, part of the National Institutes of Health, appears in the August 25, 2004 issue of the Journal of the American Medical Association (JAMA).

The four year investigation, which was coordinated by the University of Pittsburgh School of Medicine and led by Richard Schulz, Ph.D., Director of the Center for Social and Urban Research at Pitt, determined that clinical intervention may greatly benefit caregivers by helping them to prepare for the placement of their relatives and by treating their depression and anxiety during the placement process.

This is the first study to provide a comprehensive analysis of the emotional turmoil caregivers experience during the transition of their loved one from home to a long-term care facility, according to Dr. Schulz. The investigators looked at a number of factors including the conditions that led to placement, the nature of contact between the caregivers and their relatives after institutionalization, and the impact of these factors on health outcomes among caregivers following the placement.

Participants of the study were recruited from six U.S. sites and included 1,222 caregiver-patient pairs. For the 180 caregivers who had to turn over care of their loved one to an institution, symptoms of depression and anxiety stayed as high as when they were in-home caregivers. These findings stand in sharp contrast to earlier findings reported by Schulz and his group showing that death of a loved one after care giving results in improvement in depression.

“Caregivers who place their loved ones in an institution do not get the sense of relief or experience the closure observed among caregivers whose loved ones pass away," said Dr. Schulz. "They continue to feel distressed because of the suffering and decline of their loved one as well as having to face new challenges such as frequent trips to the long-term facility, reduced control over the care provided their relative, and taking on responsibilities such as coordinating and monitoring care," he added.

According to Dr. Schulz, "cognitive and functional declines are common in patients who go into long-term care, and caregivers often blame themselves for this decline and question their decision to institutionalize their loved one."

Caregivers who were married to the patient and those who visited most frequently had the most difficult transition. Spouses reported higher levels of depression both before and after placement and more anxiety after placement than their non-spouse counterparts. Almost half of the caregivers in the study visited the patient daily and continued to provide some form of physical care during their visits.

The study recommends that spouses, caregivers who remain actively involved with the care recipient, caregivers who have high levels of depression, and those who lack adequate support from others should receive interventions. "We need to help caregivers who place their relatives, said Dr. Schulz.. "We need to treat their emotional distress, educate them about the nature of long-term care facilities and their impact on patient functioning, engage them in end-of-life planning, and prepare them for the eventual death of their loved one," he added.

The patients in this study were all diagnosed with moderate to severe Alzheimer's disease and had a median age of 80 years. Caregivers were mostly female with a median age of 63 years. The sample was 56 percent white, 24.2 percent African American, and 19 percent Hispanic; most were spouses or children.

The researchers found that African American and Hispanic caregivers were less likely to place their relative in a facility than whites; caregivers reporting greater burden were more likely to place their loved one in long-term care; caregivers who reported that their care giving experience made them feel useful and important were less likely to place their relative in a facility.

“The findings of Dr. Schulz and his associates are particularly relevant as Americans live longer and the number of families faced with placing their loved ones into institutional care grows," said NINR Director Patricia A. Grady, PhD, RN, FAAN.. "Knowing that these caregivers are vulnerable to ongoing depression and anxiety following such a placement, health professionals can make a difference in these people's wellbeing by helping them with their emotional distress, and by helping them prepare for and deal with these often difficult transitions," Dr. Grady added.

MSNBC Dec. 6, 2004

63.Food for thought: Can diet protect memory?
Smart eating choices may prevent age-related brain decline

By Molly Masland
Health Editor

As concern over Alzheimer's disease grows, more Americans are turning to expensive and potentially unsafe supplements that claim to enhance memory. But prevention of age-related memory loss may be no further away than your refrigerator, and no more expensive than a bag of groceries, experts say.
With the aging population of baby boomers in the United States, more research is being done than ever before on diseases such as Alzheimer's and other forms of dementia. Scientists are developing a better understanding of why memories fade, and along the way they are finding new ways to combat the decline.
For one thing, research increasingly suggests that diet may be important in preventing Alzheimer's.

Inside the aging process
As the brain ages, it loses the ability to protect itself from the barrage of commonplace dangers it faces every day, particularly inflammation and oxidation, a process which allows damaging free radicals to attach themselves to cells.
While it's not entirely clear what causes Alzheimer's disease, amyloid plaque - a goopy, fibrous substance akin to fur balls in the brain - plays a key role. As the plaque builds up, it causes more oxidation and inflammation, and begins to kill off brain cells.
In addition, brain cells often stop communicating with each other as people age, making it harder for the brain to process thoughts, retain short-term memory and create new cells.
"Old neurons are like old married couples - they don't talk to each other very much anymore. They just sit in the room with the remote and stare at the TV," says Dr. James Joseph, director of the Neuroscience Lab at the Human Nutrition Research Center on Aging at Tufts University in Boston.

Older dogs can learn new tricks
While research in the field of aging and nutrition is still in its infancy, scientists have found that diet may help minimize the brain's sensitivity to oxidation and inflammation, as well as improve brain cells' ability to communicate with each other.
One of the most intriguing areas of research involves the role of antioxidants, potent chemicals in plants that protect against free radicals, highly active molecules that damage cells. Antioxidants are what give fruits and vegetables their bright colors. Plants produce these chemicals to protect themselves from environmental insults, such as pollution, and when humans eat plants, they also reap the protective benefits.
In a study involving about 70 beagles, Dr. Carl Cotman, director of the Institute for Brain Aging and Dementia at the University of California, Irvine, found that older dogs fed a diet rich in antioxidants over several years were able to perform tasks - and learn new tricks - far better than fellow canines fed a normal diet.
“We rejuvenated a capacity in the aging brain which wasn't there in the beginning and wasn't coming back on its own," says Cotman. "It indicated the brain has a capacity to recover some age-related loss of cognitive function."
Moreover, MRI scans later revealed structural changes in the brains of the dogs on the antioxidant diet, most notably a decrease in the buildup of amyloid plaque.

A cornucopia of benefits
While it's unclear exactly how the antioxidants affected the dogs, Joseph, co-author of "The Color Code: A Revolutionary Eating Plan for Optimum Health," says many fruits and vegetables primarily valued for their powerful antioxidants may in fact provide multiple benefits for the aging brain. They may not only slow oxidation, but may also act as anti-inflammatory agents, make the brain less vulnerable to amyloid plaque, improve communication between neurons and allow the brain to regenerate - all of which contribute to better memory in old age.
Purple fruits and vegetables, such as blueberries, cranberries and Concord grapes, may be especially beneficial for the brain, says Joseph. In a study on aging mice genetically engineered to develop Alzheimer's, Joseph was able to improve their cognitive function by feeding the animals a diet high in blueberries.
In addition to better memory and motor skills, Joseph found that the mice had fewer signs of damage from oxidation and inflammation in their brain tissue than did mice fed a standard diet. They also had higher levels of chemicals necessary for brain cells to regenerate and communicate.
While it's still too early to tell if the animal studies apply to humans, it's quite possible that "what's going on in the rat may be what's going on in a human," says Joseph, who published the results of the study last year in the journal Nutritional Neuroscience.
In addition to particular fruits and vegetables, scientists believe that curcumin, a spice used in India and known for its anti-inflammatory effects, may prevent memory loss. Curcumin is what gives yellow curry its bright color and is frequently used as a natural food dye.
In a study on genetically engineered mice, Dr. Greg Cole, associate director of the Alzheimer's Center at the University of California, Los Angeles, found that curcumin helped reduce amyloid plaque in the animals, and also limited damage from oxidation and inflammation. The results of the study were published in 2001 in the Journal of Neuroscience. A clinical trial is now under way at UCLA to test curcumin in people and find an effective dose.
New research has also shown that B vitamins, such as niacin and folic acid, are vitally important to brain function and may help keep the mind sharp. Found in a range of foods, including lean meat, fish, legumes, dairy products, grains and green, leafy vegetables, B vitamins appear to help control inflammation and may play a role in the development of new brain cells.

Supplements may not do the same
Given the growing evidence of the benefits of antioxidants and other chemicals on the brain, why not just take specific supplements to prevent memory loss?
Most researchers caution that sources of antioxidants from food are far more effective - and safer - than supplements. Although it isn't precisely known how the chemicals work, it's believed that they act in combination with one another.
In addition, different chemicals in plants protect against different kinds of damage, and there may be additional but as yet undiscovered substances in plants that work with antioxidants to provide the protective effects.

(c) 2004 MSNBC Interactive

MSNBC Dec. 6, 2004

64.Good for the heart, good for the brain
Cutting cholesterol, eating fish may keep mind sharp

By Molly Masland
Health Editor

Besides eating more fruits and veggies, avoiding saturated fats and trans fats may also help prevent age-related memory loss. When it comes to the amount of fat in the diet, researchers have found that what's good for the heart is good for the brain. In the same way that reducing levels of bad cholesterol can prevent arteries from becoming ravaged by atherosclerosis, low cholesterol levels in the diet may also help protect brain cells.
In a study involving rat brain cells, Dr. Mark Mattson, chief of the Laboratory of Neurosciences at the National Institute on Aging in Baltimore, found that reducing cholesterol and ceramide, a form of fat, made the cells more resistant to the destructive effects of the amyloid plaque. And in a study of mice genetically engineered to develop Alzheimer's, the NIA scientists found that how much the rats ate also was significant.
“What we find is that a high-fat diet is bad for learning and memory, and the low-calorie and intermittent fasting diets preserve learning and memory," says Mattson, whose research was presented last month at the Society for Neuroscience annual meeting in San Diego.
Although an actual cause and effect has not yet been proven, cholesterol appears to promote the production of amyloid plaque and contains an enzyme that the plaque needs to grow. It also promotes harmful oxidation and can cause damage to cell membranes.

A fishy story
While diets high in cholesterol are bad for the brain, getting plenty of omega 3 fatty acids, found primarily in fish, is vital for a healthy noggin, researchers say. In particular, a component of omega 3 fatty acids known as DHA, or docosahexaenoic acid, is key.
DHA is found in high concentrations in the brain and is needed for healthy cognitive function. It is widely believed to have an anti-inflammatory effect and is known to have a protective benefit on the heart. The most concentrated source of DHA is oily fish, such as salmon, tuna, herring, sardines and mackerel.
In an observational study conducted at Rush University Medical Center in Chicago, Dr. Martha Clare Morris, associate professor of internal medicine, found that people who ate fish once a week had a 60 percent reduction in the risk of Alzheimer's compared with people who never ate fish. Eating fish more than once a week did not appear to provide additional benefits.
Other studies have found similar results. Hoping to learn more about the processes behind DHA's apparent benefits, Cole conducted a study in which one group of aging bioengineered mice were fed food high in DHA while another group ate a standard diet and a third group ate a diet deficient in DHA. The mice fed a diet high in DHA performed better on memory tests and had reduced levels of amyloid plaque in their brains. The mice fed a diet low in DHA performed poorly on memory tests and also showed damage in the areas where brain cells communicate.

What about toxins?
Despite the protective effects of eating fish, many people may worry about the potential dangers of fat-soluble toxins such as mercury and dioxins. Most researchers don't have an answer to this conundrum except to point out that the health benefits for populations of people who eat lots of fish, such as the Japanese, appear to outweigh the risks.
For those consumers willing to pay extra, fish oil or purified DHA may offer similar benefits, although it's unclear if they're as beneficial as eating fish itself.
Cole says the best solution would be to consume the kind of DHA used in infant formulas, which is made from farmed marine algae.

(c) 2004 MSNBC Interactive

Friday, December 10, 2004 THE ORANGE COUNTY REGISTER

65.Focus on Alzheimer's shifts from treatment to prevention The number of Americans with the disease could triple in the next 50 years.

By MAYRAV SAAR
http://www.ocregister.com/ocr/2004/12/12/

For years, Alzheimer's disease research centered around treating the ill: reducing plaques in the brain, reversing the deterioration that had already set in.
But as baby boomers approach the age when Alzheimer's begins, the focus has shifted from the ill to those who could become ill - from treatment to prevention.
About 40 percent of Alzheimer's patients have a genetic predisposition to the disease, but few adults have any way of knowing whether it will hit. About 5 million Americans have Alzheimer's; in less than 50 years, that number could jump to 16 million.
But recent studies suggest - and a few new clinical trials are trying to prove - that Alzheimer's disease does not have to be a land mine along the road to old age. A new book by Newport Beach neuroscientist Daniel G. Amen and UC Irvine neurologist Dr. William Rodman Shankle suggests that there are ways to actively prevent the disease while you're young.
"It's been more and more in the spotlight because strategies are coming up that seem partially effective," said Carl Cotman, a UCI neurologist and board member of the Alzheimer's Association of Orange County. "It's driven by research progress in the field and the recognition that later in the disease you're notgoing toturn the disease around."
Prevention has even become a mandate of the nat ional Alzheimer's Association, said Bill Thies, vice president of medical and scientific affairs for the national group, based in Chicago.
"More attention has been paid to the key issues. What is it that causes this disease, and is there anything we can do about it?" Thies said.
The trick may be to focus on people 30 years or more before symptoms set in, when the disease first begins its campaign against the brain, said Amen, co-author of the new book "Preventing Alzheimer's."
"What we do early in life affects us at the end of our lives," Amen said.
Amen and Shankle call the concept "prevention by delay," meaning people can keep Alzheimer's disease at bay for so long they'll die of other causes before dementia can take hold.
Most of the recommendations probably sound familiar:
Eat right.
Exercise.
Lower your cholesterol and blood pressure.
Take your vitamins.
It's common-sense stuff for heart health or for people trying to avoid diabetes. Now research is showing that common tips for healthy living can do wonders for your brain.
In a study published in May in the journal Gerontology, UCI researchers found that antioxidant-rich foods literally helped old dogs learn new tricks.
Swedish researchers last month found that lifelong obesity is associated with an increased risk of Alzheimer's disease and other forms of dementia for women.
And doctors theorize that keeping the heart healthy helps keep enough blood pumping to the brain to prevent damaging cell death.
National clinical trials, including several at the UCI Medical Center, are underway to test whether antioxidants, estrogen, ibuprofen and folates can help prevent memory loss.
While the studies have been more effective in mice than in humans so far, researchers are confident that Alzheimer's can be prevented. The Alzheimer's Association six months ago launched its "Maintain the Brain" campaign, an effort aimed at people in their 40s and 50s to promote good habits in hopes of reducing the number of future Alzheimer's cases.
"If we can delay the disease by five years, we could cut the number of cases of Alzheimer's in half," Thies said.
EARLY DETECTION
While some researchers are on the trail of new drugs to disrupt the disease before it does the most damage, others are trying to find ways to diagnose it earlier. The combination of these efforts could lead to a way to preventing the disease from taking hold at all, Thies said.
Early detection would have helped Pat Van Dyke. Though she's only 52, her memory loss had gotten so bad she said she was in danger of losing her job.
"My boss told me, 'Nobody wants to work with you,' " said Van Dyke, who worked as a high-ranking administration assistant at a sales office before being demoted to a receptionist position. "That was a Friday, and I cried all weekend."
Faced with firing, Van Dyke sought medical attention and was diagnosed in March with Alzheimer's disease.
Van Dyke, of Anaheim, said she was in shock initially but knowing her diagnosis helped her cope.
"In a way it was almost a relief," Van Dyke said. "Otherwise you think you're stupid. I got to the point where I was badgering myself a whole lot, and that's unhealthy."
Now, Van Dyke is determined to do something about the disease. She takes Aricept, a drug that helps delay symptoms from worsening. She also takes daily doses of vitamins E and C, which are believed to help prevent memory loss and dementia. And she keeps her cholesterol low.
Van Dyke said she plans to exercise again when she leaves work in January, and she'll continue volunteering, reading newspapers and doing crossword puzzles to keep active.
"I am going to do everything I can to stay healthy and take care of myself and learn as much as I can," she said. "The end result will probably be the same, but I'm going to enjoy everything I can while I can."
Amen said the kind of prevention methods Van Dyke is taking would be even more effective well before middle age. This month, he will begin teaching a 12-week brain-science course to students at Back Bay High School in Costa Mesa.
"I think we have no love, honor or respect for the brain in our society," Amen said. "Think about letting children with developing brains hit soccer balls with their heads. We feed them high-fat diets, put them under stress. That's not loving the brain."
Thies and other Alzheimer's experts said they're not sure prevention needs to begin in high school, but it certainly couldn't hurt. And it needs to begin sometime.
"It's never too early and probably never too late to start," Thies said. "The earlier you start to change habits, the easier it gets to be. But I think you don't want people to become discouraged about whether it will make a difference."

The Australian　December 14, 2004

66.Skin test　detects Alzheimer's
By Sharon Labi　

AUSTRALIAN researchers say they have developed a skin test that can identify people with early Alzheimer's disease and those at risk of developing dementia.
Professor Zeinab Khalil of the National Ageing Research Institute at the University of Melbourne said Alzheimer's was a common problem but modern medicine had no reliable early diagnostic test.
"For researchers, there are difficulties trialling new medications because you're never absolutely sure your subjects have the condition," Prof Khalil said.
"We think we've found the holy grail of an early Alzheimer's test."
Prof Khalil said that in patients with Alzheimer's disease, a gunky material called amyloid built up around nerve cells and seemed to interfere with the way they worked.
Amyloid is thought to cause inflammation and damage to the tiny blood vessels that supply oxygen to the nerves.
Researchers at the University of Melbourne found this blood vessel damage could be detected outside the brain, on the skin.
They studied blood supply to the skin in people with confirmed Alzheimer's disease, people at risk of the condition, people with other forms of dementia and healthy elderly people.
"What we found is that the skin test was very good at identifying people with early Alzheimer's disease and, indeed, elderly people with mild memory impairment who are at risk of developing dementia a few years later," Prof Khalil said.
"This test has been in the making since 1992. We started with basic laboratory research which we then moved to the clinic to assess in patients.
"That was over five years ago and in that time we've shown that the results are reliable and repeatable.
"It is really exciting, especially since it's an Australian development."
The researchers will present their findings at the second International Conference on Healthy Ageing and Longevity to be held in Brisbane next March.

Alzheimer's Association, Dec. 13, 2004

67.Inability to smell may be early warning for Alzheimer's 　

An inability to identify 10 specific smells may help predict which individuals with mild cognitive impairment (MCI) will go on to develop Alzheimer's disease, according to a Dec. 13 presentation at the annual meeting of the American College of Neuropsychopharmacology.

Inability to detect those smells was a better predictor of progression to dementia than was shrinkage in the hippocampus, a key part of the brain affected by Alzheimer's disease. The researchers also found that having APOE-e4, a gene variation linked to an increased Alzheimer risk, was not a significant predictor of progression.

“There is no question that we need better ways to diagnose dementia as well as to identify who with MCI will progress to Alzheimer's disease," notes William H. Thies, Ph.D., Alzheimer's Association vice president, medical and scientific affairs. "It's conceivable that smell evaluation could one day play a role in this effort, because changes in the ability to smell have been widely noted in Alzheimer's disease. The notion that some smells might be more severely impaired than others is plausible, given that Alzheimer's disease tends to affect certain nerve cell circuits more severely than others.

“But we are a very long way from using smell evaluation as a reliable assessment tool. This study is an interesting step in that direction, but at this point it's extremely preliminary. The data have not been peer reviewed by independent experts or published anywhere. And the test has not been standardized or validated across a large group of people. Individuals should under no circumstances make any assumptions about their cognitive health based on their ability or inability to detect any odors," Thies cautions.

The study was reported by principal investigator Davangere P. Devanand, M.D., whose work was supported by the National Institute on Aging (NIA) as well as by the Alzheimer's Association. The researchers recruited 150 older adults with MCI and 62 with no evidence of cognitive problems, then periodically tested participants' ability to identify a variety of smells over an average of four years. Results suggest that scents of lemon, lilacs, leather, strawberries, smoke, soap, menthol, clove, pineapple, and natural gas were the best predictors of who would eventually develop Alzheimer's disease.

Individuals with MCI have problems with memory or other thinking skills serious enough to show up on tests but not severe enough to interfere with customary daily activities. MCI often, but not always, progresses to Alzheimer's disease. At this time, smell evaluation remains an experimental approach to predicting progression of MCI. Many factors can affect the sense of smell, including upper respiratory infections, current or past smoking, and normal variations in individual sensitivity.

MONDAY, Jan. 10 (HealthDayNews)

68.Weight Loss Signals Impending Alzheimer's It may point to dementia years before diagnosis, study finds

By Steven Reinberg
HealthDay Reporter

Weight loss, which has been previously associated with dementia and Alzheimer's disease, may begin up to six years before diagnosis, a new research suggests.
This is the first study to show that weight loss is associated with early cognitive impairment and that it increases as dementia worsens. The researchers said weight loss may contribute to, or speed up dementia, but it is not the primary cause of the condition.
The study was done among a group of Japanese-American men, and appears in the January issue of the Archives of Neurology.
"As a group, the men decrease in weight as they get older, but the men who got demented lost even more weight," said study co-author Lenore J. Launer, an investigator and chief of the Neuroepidemiology Section at the National Institute on Aging. "This suggests that when people are getting older, extra care needs to be given to make sure that they are getting an adequate diet," she added.
In their study, Launer and her colleagues collected data on 1,890 Japanese-American men, 77 to 98 years of age, who were part of the Honolulu-Asia Aging Study. Over 34 years, 112 of the men were diagnosed with dementia.
During the study, the men were examined six times. At the three most recent examinations, their weight was assessed and they were also tested for signs of dementia.
"Individuals who developed dementia had a significantly greater weight loss than individuals who did not develop dementia six years before the diagnosis," Launer said.
Many of the men with dementia had lost at least 11 pounds, which was about 10 percent of body weight among the men. This weight loss happened from two to six years before a clinical diagnosis of Alzheimer's or vascular dementia, the researchers noted.
Among men who did not develop dementia, only 12 percent had lost that much weight, the researchers found.
The increased weight loss among those with dementia may signal that something in the brain that controls appetite or metabolism is affected. "Weight loss is a sign of dementia," she said. "Not that it is leading to dementia."
Launer does not believe that weight loss causes Alzheimer's, or that maintaining weight can slow the process of increasing dementia. However, maintaining body weight may reduce the severity of other medical problems -- including falls, poor wound healing, and increased physical dependence -- that can accompany dementia, she said.
Launer added that she's not sure if these findings are applicable to other groups of men or women. "Further study is needed," she said.
Dr. Michael Grundman, head of the Alzheimer's Disease Prevention Program at Elan Pharmaceuticals in San Diego, said, "It is pretty clear that losing weight happens long before Alzheimer's is diagnosed."
"It [the research] suggests that people with mild cognitive impairment are already losing weight," he added.
According to Grundman, who wrote an accompanying editorial in the journal, weight loss could be a marker of impending dementia. "If doctors were to recognize this, then this is something they should think about in terms of cognitive decline or Alzheimer's disease," he said.
Weight loss may contribute to, or speed up dementia, Grundman said, "but it is not the primary cause of dementia." However, he suggested that maintaining body weight can help slow the progression of Alzheimer's.
"The weight loss that is associated with Alzheimer's is not normal," Grundman said. "There should be efforts to maintain body weight. Probably the earlier it is recognized that weight loss is occurring, the sooner you can intervene, and the potential benefits would be greater," he said. "It's not proven yet, but it just makes sense."

springfield.news-leader.com January 21, 2005

69.Study offers hope for Alzheimer's patients-Researchers found clearing plaque from brains of mice reduced swelling, led to quick recovery.-

By Jim Salter
Associated Press

St. Louis - Brain cells in mice recovered rapidly after brain plaques characteristic of Alzheimer's disease were removed, offering hope that plaque-clearing treatments could benefit patients with the disease, Washington University researchers said Thursday.
Results of the study will appear in the Feb. 5 issue of the Journal of Clinical Investigation.
No one knows for sure if the sticky plaque - amyloid beta peptide - is the true cause of Alzheimer's, a brain degeneration disease that eventually robs victims of memory and the ability to communicate and care for themselves. About 4.5 million Americans have the disease.
But the plaque is a prime suspect, and several companies are developing drugs to target the buildup.
Researchers at Washington University injected mice with an antibody that cleared plaque in parts of the brain. Where the plaque was cleared, swelling on nerve cell branches disappeared quickly, the researchers said.
"These swellings represent structural damage that seemed to be well established and stable, but clearing out the plaques often led to rapid recovery of normal structure over a few days," said Dave Holtzman, senior author of the study and head of the Department of Neurology at Washington University.
"This provides confirmation of the potential benefits of plaque-clearing treatments and also gets us rethinking our theories on how plaques cause nerve cell damage," Holtzman said.
Holtzman was among scientists who previously regarded plaque damage to nerve cells as something that only needed to happen once. Instead, the results suggest that plaques might not just cause damage but actively maintain it, he said.
To connect brain cell damage to plaque development, lead author Robert Brendza showed that as plaques appeared, nearby branches of nerve cells developed bumps and swellings.
Brendza injected antibodies directly onto the surface of the mouse brains. The antibodies cleared the plaques from the region of the injection, confirming earlier research.
But as Brendza monitored the swellings for three more days, he found a surprising result.
"We thought that clearing the plaques would halt the progression of the damage - stop the development of new swellings," Brendza said. "But what we saw was much more striking: In just three days, there were 20 to 25 percent reductions in the number or size of the existing swellings."
The rapid ability of the nerve cells to regain their normal structure could indicate that the cells are constantly trying to restore their normal structure, the researchers said. They cautioned that more research is needed to determine whether similar effects will occur in humans.
Dr. Sam Gandy, vice chairman of the Chicago-based Alzheimer Association's Medical and Scientific Council, called the finding "a pretty exciting advance."
"It shows that one of the long-standing structural abnormalities that was used to really define the disease is not something that's permanent and in fact it's reversible," Gandy said.
The largest swellings were the least likely to heal in the mice. Brendza will study whether additional treatment can prompt their recovery

January 22, 2005　 NYT

70.Safety Concerns Reported on J.& J. Alzheimer's Drug
By ANDREW POLLACK

Regulators are reviewing the safety of the Alzheimer's disease drug Reminyl after data from two clinical trials indicated that people taking the drug had a much higher death rate than those taking a placebo.
The review was announced yesterday by Johnson & Johnson, which said it was in discussions with the Food and Drug Administration and regulators in Europe and Canada.
The trials, which involved about 2,000 patients in 16 countries, were looking at whether Reminyl could be used to treat mild cognitive impairment, a form of memory loss that is often a precursor to Alzheimer's disease. Reminyl is approved in 69 countries as a treatment for mild to moderate Alzheimer's but not for mild cognitive impairment.
In the trials, which lasted two years, 15 patients taking Reminyl died compared with 5 taking the placebo. There were various causes of death but many were from heart attacks and strokes, a company spokeswoman, Carol Goodrich, said.
The announcement comes at a time of heightened concern over the safety of widely used drugs after the withdrawal from the market of Merck's pain reliever, Vioxx, which studies indicated posed an increased risk of heart attacks and strokes.
Johnson & Johnson said that overall number of deaths in the trials was low for the elderly population in the trial and that the incidence of serious side effects was the same for patients getting the drug and the placebo. Also, it said, the investigators in the trials had not thought the drug caused any of the deaths.
The results were reported to regulatory authorities in August and presented at medical conferences, Ms. Goodrich said. Asked why an announcement was being made only now, she said regulators in Europe and Canada had met with the company this week to obtain more data and were preparing to post information about the trials on their Web sites.
Ms. Goodrich said the information would still support the use of the drug for Alzheimer's disease.
A spokeswoman for Health Canada, Carole Saindon, said data was being analyzed and conclusions would be posted when ready. "It's very important that patients don't stop taking the medication without consulting their doctor first," she said.
A spokeswoman for the F.D.A., Kathleen Quinn, said the agency was looking at the data. European regulators could not be reached.
Reminyl was approved on the basis of six-month studies but the mild cognitive impairment trials lasted two years, increasing their chances of detecting side effects. Nevertheless, the Johnson & Johnson analysis said the excess of deaths in the mild cognitive impairment trials was evident by six months, while no such excess was seen in the Alzheimer's trials.
Reminyl, known generically as galantamine, was developed with Shire Pharmaceuticals of Britain. Sales for Johnson & Johnson are estimated at about $200 million a year. The drug, extracted from daffodil bulbs, is a cholinesterase inhibitor, which works by increasing the levels of acetylcholine, a chemical that transmits nerve signals in the brain. Others in this class include Aricept, sold by Pfizer and Eisai, and Exelon from Novartis.
Public Citizen, the watchdog group, recommends against using Reminyl or other drugs in its class, saying they have minimal benefit and the effectiveness and safety of taking them longer than six months is not known, according to Sidney Wolfe, director of health research.
There are no drugs approved for mild cognitive impairment but drug companies are pursuing that condition in hopes of preventing people from sliding into Alzheimer's.

BBC : Tuesday, 1 February, 2005, 09:28 GMT

71.Hope over early Alzheimer's test

Tests carried out on humans suggest people with Alzheimer's disease could be diagnosed before symptoms start to appear, US doctors say.
Patients are often not diagnosed until the later stages, after brain damage.
But researchers said a sensitive test to detect a type of protein molecule could identify the disorder early after successfully trialling it on 30 people.
The team at Northwestern University in Chicago have claimed Alzheimer's could be treated if caught early.
Lead researcher William Klein said traditional diagnosis came too late for people with Alzheimer's.
"We think the accumulation of the molecules is likely to be the first biomarker in Alzheimer's disease, and now this extraordinary powerful detection technology has changed what we think might be possible."
One in 20 people over 65 years old and a fifth of those over 85 have Alzheimer's.
The team believes molecules, called ADDLs, are present at high levels in the cerebrospinal fluid at the onset of Alzheimer's and block memory function, the Proceedings of the National Academy of Sciences reported.
Using a highly sensitive test, which employs bionanotechnology, the team was able to check the levels of ADDL in 30 individuals and found they were consistently higher in people with the disease.

'Encouraging'
Researchers are now hoping to develop a blood or urine test to detect the molecules, as cerebrospinal fluid is more difficult to obtain.
Alzheimer's Research Trust deputy chief executive Harriet Millward said an accurate test for Alzheimer's in the early stages would help treatment, but she said there was still a long way to go.

"This research is encouraging, but it is too soon to say how useful this particular technique will be as a diagnostic test.
"The results will need to be validated in larger numbers of people.
"Taking cerebrospinal fluid from people is not very practical and can be painful, so scientists hope to develop the technology for blood or urine samples.
"It is also not yet clear whether this method will enable doctors to differentiate between Alzheimer's and other forms of dementia for which future treatments may differ."

EurekAlert! date: 31-Jan-2005 Society of Nuclear Medicine

72.New nicotine-like imaging agent holds promise in PET studies, may help diagnose Alzheimer's disease

RESTON, Va.-- The chemical nicotine--a main ingredient in tobacco--may hold promise in the early diagnosis of Alzheimer's disease, give insight into therapeutic interventions for nicotine addiction and possibly complement the diagnosis of certain forms of lung cancer, according to a study in the January issue of the Society of Nuclear Medicine's Journal of Nuclear Medicine.
Researchers are examining nicotine's cognitive, behavioral and addictive actions, and, by looking at targets in the brain where nicotine acts, researchers hope to address several major health problems, said SNM member Jogeshwar Mukherjee, Ph.D., associate professor in residence at the department of psychiatry and human behavior, Brain Imaging Center, at the University of California at Irvine (UCI). A team of researchers from UCI and the Kettering Medical Center in Dayton, Ohio, found that imaging studies with a new fluorine-18 labeled imaging agent, nifrolidine, complement other ongoing positron emission tomography (PET) studies currently underway with nicotine-like PET imaging agents.

Nifrolidine was developed to specifically bind to a receptor (protein) that is present in the human and nonhuman brain; this receptor is involved in several brain functions, particularly cognition and certain aspects of learning and memory, according to Mukherjee. By binding at the same place as nicotine, nifrolidine helps to measure how and where nicotine acts. PET studies can be performed with nifrolidine to provide information on the receptor present in various regions of the brain. "Research has shown that with Alzheimer's disease there is a gradual loss of these receptors; therefore, there is a potential of early diagnostic value in nifrolidine-PET imaging," he said.

In addition, nicotine addiction and lung cancer may be linked to this receptor. The availability of a good PET imaging agent for this receptor will allow preclinical and clinical studies, leading to better understanding of different medical conditions and eventually helping in their diagnosis and treatment, said Mukherjee.

Additional research and work with animal subjects must be completed before this tracer can be used to demonstrate applications in human studies, said the co-author of "Synthesis and Evaluation of Nicotine α4β2 Receptor Radioligand, 5-(3'-18F-Fluoropropyl)-3-(2-(S)- Pyrrolidinylmethoxy) Pyridine, in Rodents and PET in Nonhuman Primate." The team plans to obtain complete toxicity and dosimetry data in order to obtain approval for conducting human studies.

"Synthesis and Evaluation of Nicotine α4β2 Receptor Radioligand, 5-(3'-18F-Fluoropropyl)-3-(2-(S)- Pyrrolidinylmethoxy) Pyridine, in Rodents and PET in Nonhuman Primate" was written by Sankha Chattopadhyay, Ph.D., Baogang Xue, M.D., Daphne Collins, B.E., and Rama Pichika, Ph.D., all at the department of psychiatry and human behavior, Brain Imaging Center, University of California, Irvine, Calif.; Rudy Bagnera, B.S., and Frances M. Leslie, Ph.D., both at the department of pharmacology, University of California, Irvine, Calif.; Bradley T. Christian, Ph.D., Bingzhi Shi, Ph.D., and Tanjore K. Narayanan, Ph.D., all at the department of PET/nuclear medicine, Kettering Medical Center, Dayton, Ohio; and Steven G. Potkin, M.D., and Jogeshwar Mukherjee, Ph.D., both at the department of psychiatry and human behavior, Brain Imaging Center, University of California, Irvine, Calif.

Feb. 2, 2005

73.Association responds to USA TODAY letter to the editor on the link between aluminum and Alzheimer's disease

Dear USA TODAY:

USA TODAY printed a letter ("Explore high-risk factors behind Alzheimer's disease," Letters, 1/31/05) that unfortunately may reinforce a myth about risk factors for Alzheimer's disease.

The link between aluminum and Alzheimer's disease (AD) has never been conclusively proven. After several decades of research, scientists have been unable to replicate the original 1960s studies showing aluminum deposits in a brain affected by Alzheimer's. The research community is generally convinced that aluminum is not a key risk factor in developing Alzheimer's disease.

Public health bodies sharing this conviction include the World Health Organization (WHO), the U.S. National Institutes of Health, the U.S. Environmental Protection Agency, and Health Canada.

For example, in its 1998 paper on Aluminum in Drinking-water, the WHO said:
"Based on current knowledge of... AD and the totality of evidence from these epidemiological studies, it was concluded that the present epidemiological evidence does not support a causal association between AD and aluminum in drinking-water (WHO, 1997)."

The U.S. government's National Institute of Environmental Health Services says:
"Much research over the last decade has focused on the role of aluminum in the development of this disease. At this point, its role is still not clearly defined." Further, it says: "Epidemiological studies attempting to link AD with exposures in drinking water have been inconclusive and contradictory. Thus, the significance of increased aluminum intake with regard to onset of AD has not been determined."

The Alzheimer's Society in London says:
"There is circumstantial evidence linking this metal with Alzheimer's disease but no causal relationship has yet been proved. As evidence for other causes continues to grow, a possible link with aluminum seems increasingly unlikely." And, "The overwhelming medical and scientific opinion is that the findings... do not convincingly demonstrate a causal relationship between aluminum and Alzheimer's disease, and that no useful medical or public health recommendations can be made, at least at present."

At the same time, there is a growing body of scientific evidence that making relatively simple changes in a number of lifestyle risk factors - many of which are familiar to people because of their link to heart disease - can encourage healthy brain aging and may reduce risk of Alzheimer's. These include:

Adopting a brain-healthy diet
Remaining socially engaged
Being mentally active
Staying physically active

In fact, several of these brain health strategies are addressed in stories in USA TODAY, including:

"A Healthy Heart Means A Healthy Mind," July 7, 2004
"Plant Foods To The Rescue," August 11, 2004
"Fishing For Answers To Alzheimer's," November 17, 2004
"Minds In Motion Stay Sharp," January 25, 2005

This careful and balanced reporting in these articles provides a valuable service to the community concerned about conquering Alzheimer's disease and related disorders.

For more information about healthy brain aging and Alzheimer's disease, people can visit www.alz.org.

William Thies, Ph.D.
Vice President, Medical & Scientific Affairs
Alzheimer's Association
Chicago

Contact:
Catherine Bryan
Director, Public Relations
Alzheimer's Association
225 N. Michigan Avenue
17th Floor
Chicago, IL 60601
312-335-4078

Reuters Feb 4, 2005

74.Constant Worry May Increase Alzheimer's Risk

By Alison McCook
NEW YORK (Reuters Health) - People who have a tendency to worry or feel very stressed out may be more likely to develop Alzheimer's disease later in life, new research reports.
The relationship between stress and Alzheimer's disease also appears to be much stronger in whites than in African-Americans, the authors note in the journal Neurology.
The nature of the connection between a tendency to worry and the memory-robbing disease is still unclear, study author Dr. Robert S. Wilson of Rush University Medical Center in Chicago told Reuters Health.
However, he said that he suspects that chronic elevations of stress hormones may damage regions of the brain that regulate both behavior under stress and memory.
Wilson emphasized that this study only connects stress and Alzheimer's, and does not prove that one causes the other. The report "does not establish that distress causes dementia," Wilson noted.
But while it's too soon to recommend that people reduce their stress to help avoid Alzheimer's disease, there are many other healthy reasons to relax, he added.
"The tendency to experience psychological distress is a trait that we all have to greater or lesser degrees," Wilson noted. "Family or friends concerned about a loved one who is chronically unhappy should encourage the person to see a qualified mental health professional."
As part of the study, Wilson and his colleagues asked 1,064 white and black people at least 65 years old about their tendency toward worry and stress, then examined them 3 to 6 years later to determine if they had developed Alzheimer's disease.
They found that people who appeared prone to feeling distressed were more than twice as likely to develop Alzheimer's disease within 3 to 6 years. The relationship between stress and Alzheimer's disease was much stronger in white participants, Wilson and his team report.
Wilson added that this is the first study to examine the link between stress and Alzheimer's disease in African-Americans.
"At this point we do not have an explanation for the racial difference, but we think the finding underscores the importance of including racial and ethnic minorities in this kind of research," he noted.
SOURCE: Neurology, January 25, 2005.

Reuters Feb 7, 2005

75.No, Nicotine Probably Doesn't Ward Off Alzheimer's

NEW YORK (Reuters Health) - The final excuse for smoking -- that it might reduce the risk of developing Alzheimer's disease -- has just been stubbed out, findings from an animal study suggest.
Past animal and human studies have indicated that nicotine exposure inhibits the formation of amyloid plaque, a key feature of Alzheimer's disease. However, the new study shows that chronic nicotine use appears to worsen the effects of a brain protein called tau, which is responsible for the fibrous tangles that are the other hallmark of the disease.
So, at best, the effects of nicotine are probably canceled out, according to the researchers.
Dr. Frank M. LaFerla, from the University of California at Irvine, and colleagues administered nicotine to a genetically engineered strain of mice that develops Alzheimer's disease.
Nicotine treatment produced an increase in nicotine receptors in the animals' brains that correlated with a dramatic rise in the aggregation and activity of the tau protein. This indicates that the disease-causing effects of tau were worsened, the team reports in the Proceedings of the National Academy of Sciences.
Moreover, in these experiments, chronic nicotine administration had no effect on levels of soluble amyloid, the researchers point out.
The results emphasize the importance of assessing nicotine's affects on all aspects of the disease, they write. "Our findings suggest that the use of nicotine as a potential therapy for Alzheimer's disease should be reevaluated."

SOURCE: Proceedings of the National Academy of Sciences, early edition February 7, 2005.

Reuters Feb 18, 2005

76.Researchers slam Astra drug Seroquel in Alzheimer's

By Ben Hirschler
LONDON (Reuters) - An antipsychotic drug frequently given to Alzheimer's patients actually worsens their illness, researchers say.
Patients given AstraZeneca Seroquel had a marked deterioration of memory and other higher brain functions compared to those on placebo, according to Professor Clive Ballard of the Institute of Psychiatry and colleagues.
AstraZeneca, Europe's third largest drugmaker, disputed the findings.
Drugs such as Seroquel, which was originally developed to tackle schizophrenia, are increasingly used to treat the personality changes and aggression often associated with Alzheimer's disease.
They are not approved by regulators for dementia but are often prescribed by doctors on an "off-label" basis for patients who develop serious behavioural problems.
In one form or another, antipsychotics are used in up to 45 percent of British nursing homes, experts estimate.
"It's a big potential threat to patient health," Ballard told Reuters on Friday.
There have been concerns that the two most commonly used antipyschotics, Eli Lilly and Co's Zyprexa and Johnson & Johnson's Risperdal, may increase the risk of stroke -- something British healthcare regulators warned about last year.
But, writing in the British Medical Journal, Ballard said Seroquel was not a viable alternative.
COGNITIVE DECLINE
His team studied 93 patients with dementia in the northeast of England over six months and found those taking Seroquel experienced a doubling in cognitive decline compared with patients given a dummy pill.
Those taking another antipyschotic in the trial, Novartis AG's Exelon, showed no worsening of their illness -- but no improvement above the placebo group.
AstraZeneca said it remained confident of Seroquel's safety and efficacy. The company criticised the design of the study, which it said was too small to given an accurate assessment and was disproportionately influenced by the results from just five patients.
It said another clinical study, presented at a conference last July and involving more than three times as many patients, had shown Seroquel was not associated with cognitive decline.
Seroquel -- sales of which jumped 33 percent last year to $2 billion (1.1 billion pounds) -- is a key revenue driver for Europe's third largest drugmaker, especially following a series of setbacks with newer drugs.
The company has been investigating expanding Seroquel's use into Alzheimer's, following tests suggesting it reduced agitation in dementia patients without risk of cerebrovascular problems.
But Ballard said the reduction in agitation demonstrated had been minor and said he would be "very concerned" if Seroquel was formally licensed for use in treating Alzheimer's disease.

HealthDay Reporter Feb. 23,2005

77.Marijuana-like Ingredient Could Slow Alzheimer's -Cannabinoids could reduce inflammation associated with disease-

By Janice Billingsley
HealthDay Reporter

WEDNESDAY, Feb. 23 (HealthDay News) -- By suppressing inflammation in the brain, a synthetic marijuana compound could potentially offer some protection against Alzheimer's disease, Spanish scientists report.
The researchers, who studied the brain tissue of deceased Alzheimer's patients, discovered that many of these patients lose the function of important cannabinoid brain receptors, which seem to guard against cognitive decline.
They further discovered in a rat study involving synthetic marijuana that when these brain receptors were working, they reduced the brain inflammation that is associated with Alzheimer's.
"This is the first time the effects of such damage have been found in Alzheimer's patients," said study co-author Maria de Ceballos, head of the neurodegeneration group at the Cajal Institute, Spain's largest neuroscience research center, in Madrid. "Previously, it has been known only in those with acute brain damage from trauma."
The findings appear in the Feb. 23 issue of The Journal of Neuroscience.
The researchers studied cannabinoid receptors called CB1 and CB2, which are proteins that bind with cannabinoids, the active ingredients of marijuana. The synergy between these receptors and cannabinoids are known to provide protective effects against inflammation in the brain.
In the first part of their study, they compared the brain tissue of deceased Alzheimer's patients to similar tissue from healthy people who had died at the same age. Those who suffered from Alzheimer's had significantly reduced functioning of their cannabinoid receptors compared to the healthy group, which meant those with the disease had lost the capacity to experience the protective effects of cannabinoids.
Then, in a series of rat experiments, the scientists found cannabinoids reduced inflammation in the brain and prevented cognitive decline.
To find this, the researchers injected amyloid, a protein that activates immune cells and leads to cognitive decline, into the brains of one group of rats. Another group of rats received injections of a control protein. A third group of rats were injected with cannabinoids along with amyloid, and a last group received cannabinoids with the control protein.
After two months, the researchers trained the rats over five days to find a platform hidden underwater. Rats treated with the control protein -- with or without the cannabinoids -- and those treated with the amyloid protein and the cannabinoids were able to find the platform. The rats treated with the amyloid protein alone did not learn how to find the platform.
The scientists further confirmed that the amyloid protein activated the rats' brains' immune cells, causing inflammation, but that the cannabinoids counteracted this effect and reduced the inflammation.
de Ceballos said the findings suggest that those who are known to be at risk for Alzheimer's could benefit from using cannabinoids to slow the progression of the disease.
But she added that much work remains to be done before this can be put to clinical use.
Alzheimer's experts also warned this is very preliminary work because it only studied tissue in animals to find the beneficial effects of the cannabinoids, and, as such, is far from an endorsement of marijuana use in preventing Alzheimer's.
"The paper doesn't reflect any thought that people should use marijuana as any kind of therapeutic agent for Alzheimer's. It would be irresponsible to suggest that," said William Thies, vice president of medical and scientific affairs for the Alzheimer's Association.
By looking at a new possible agent that could be useful in moderating the pathology of Alzheimer's, he said, the study joins others examining the possible ways that the disease advances, including the effects of cholesterol, inflammation and the presence of amyloid proteins.
"Certainly every one of these papers that gives us new possibilities to explore is welcome," he said.
ore information

SOURCES: Maria de Ceballos, Ph.D., neurodegeneration group, Cajal Institute, Spanish Council for Scientific Research, Madrid, Spain; William Thies, Ph.D., vice president, medical and scientific affairs, Alzheimer's Association, Chicago; Feb. 23, 2005, Journal of Neuroscience

Last Updated: Feb-23-2005
Copyright (c) 2005 ScoutNews LLC. All rights reserved.

HealthDay News Feb-24-2005
78.Nerve Cell 'Traffic Jam' May Trigger Alzheimer's-Neural clogs appear much earlier in disease than thought -

By E.J. Mundell
HealthDay Reporter

THURSDAY, Feb. 24 (HealthDay News) -- Like cars backed up on a freeway, blockages in nerve cell signals may lead to the neurological traffic jam that is Alzheimer's disease, researchers say.
The research is preliminary, but a new study in mice suggests this type of neural backup occurs much earlier in the disease than previously thought. It may also help trigger the buildup of beta amyloid protein plaques that is the hallmark of Alzheimer's, the researchers believe.
The findings "point out that this transport system [nerve cell signaling] gets disrupted in Alzheimer's," explained Dr. Bill Thies, vice president of medical and scientific affairs at the Alzheimer's Association.
"The researchers propose that it's this disruption that ultimately triggers the amyloid buildup," he said.
While he labeled the findings "outstanding science," Thies cautioned that this remains just one of many theories as to the exact cause of Alzheimer's. He also stressed that any therapies based on these findings remain years away.
Reporting in the Feb. 24 issue of Science, researchers at the University of California, San Diego (UCSD) focused their efforts on axons -- long, skinny neural highways that pass biochemical messages between nerve cells throughout the body.
Scientists have long observed that axon blockages are a characteristic feature of late-stage Alzheimer's. However, the UCSD team say they have now spotted these globular axonal "defects" in mice more than a year before the rodents develop Alzheimer's-like symptoms.
Their early appearance now points to axon blockages as a potential cause, not effect, of the brain-robbing illness, they say.
The findings yielded another intriguing possibility. In Alzheimer's, the buildup of amyloid plaques within brain tissue is accompanied by a second aberration -- the accumulation of neurofibrillary 'tangles' composed of another protein, called tau.
Tau is also "a protein that appears to regulate traffic within axons," study senior author Lawrence S.B. Goldstein noted in a written statement. That suggests these tau-related blockages within axons "may promote the generation of excess amyloid beta, the protein in amyloid plaques," he said.
According to Thies, "people have been trying to figure how plaques and tangles fit together" in Alzheimer's for a long time. While many believe amyloid deposits lead to tau tangles, others suspect it works the other way around. "There's still no agreement," he said.
"But this paper suggests that axon transport [blockage] is critical in creating amyloid," Thies said. "So, if you correct the tau problem in the axons, you'll correct the amyloid problem."
Unfortunately, no safe, effective agents to untangle this transport mechanism exist, Thies said, partially because most pharmaceutical companies continue to focus on amyloid in their search for effective Alzheimer's drugs.
Right now, Thies said, research into ways to fix impaired tau transport "is on the cutting edge of what people are working on."
"So, this is not going to be in your drugstore tomorrow," the Alzheimer's expert stressed. "It's really outstanding science, but how it fits into the overall picture of trying to treat the disease -- that's still in the offing."
Still, he said this and other discoveries should give patients with Alzheimer's -- and their loved ones -- real reason for hope.
"Alzheimer's is a reasonably complex disease hitting the most complex organ in the body, so we're going to have to know a lot about it," Thies said. "But the fact is that, right now, there are a tremendous number of potential new agents out there."
"We have so many potential pathways, and some of them are going to get us through to the other side," Thies said. "To me, that's the biggest reason for enthusiasm."

SOURCES: Bill Thies, M.D., vice president, medical and scientific affairs, Alzheimer's Association; statement by Lawrence S.B. Goldstein, Ph.D., Department of Cellular & Molecular Medicine, University of California, San Diego; Feb, 24, 2005, press release, University of California, San Diego; Feb. 24, 2005, Science

EurekAlert : 7-Mar-2005

79.Researchers discover link between insulin and Alzheimer's
Discovery that insulin is produced in the brain raises possibility of Type 3 diabetes

Providence, RI ? Researchers at Rhode Island Hospital and Brown Medical School have discovered that insulin and its related proteins are produced in the brain, and that reduced levels of both are linked to Alzheimer's disease. The findings are reported in the March issue of the Journal of Alzheimer's Disease (http://www.j-alz.com), published by IOS Press.
"What we found is that insulin is not just produced in the pancreas, but also in the brain. And we discovered that insulin and its growth factors, which are necessary for the survival of brain cells, contribute to the progression of Alzheimer's," says senior author Suzanne M. de la Monte, a neuropathologist at Rhode Island Hospital and a professor of pathology at Brown Medical School. "This raises the possibility of a Type 3 diabetes."

It has previously been known that insulin resistance, a characteristic of diabetes, is tied to neurodegeneration. While scientists have suspected a link between diabetes and Alzheimer's disease, this is the first study to provide evidence of that connection.

By studying a gene abnormality in rats that blocks insulin signaling in the brain, researchers found that insulin and IGF I and II are all expressed in neurons in several regions in the brain.

Additionally, researchers determined that a drop in insulin production in the brain contributes to the degeneration of brain cells, an early symptom of Alzheimer's. "These abnormalities do not correspond to Type 1 or Type 2 diabetes, but reflect a different and more complex disease process that originates in the CNS (central nervous system)," the paper states.

By looking at postmortem brain tissue from people diagnosed with Alzheimer's disease, researchers discovered that growth factors are not produced at normal levels in the hippocampus ? the part of the brain responsible for memory. The absence of these growth factors, in turn, causes cells in other parts of the brain to die. Reserachers found that insulin and IGF I were significantly reduced in the frontal cortex, hippocampus and hypothalamus ? all areas that are affected by the progression of Alzheimer's. Conversely, in the cerebellum, which is generally not affected by Alzheimer's, scientists did not see the same drop in insulin and IGF I.

"Now that scientists have pinpointed insulin and its growth factors as contributors to Alzheimer's, this opens the way for targeted treatment to the brain and changes the way we view Alzheimer's disease," de la Monte says.

In an accompanying review article, de la Monte and accompanying author Jack Wands, MD, of Rhode Island Hospital and Brown Medical School, write that "there is a genuine need for thorough and comprehensive study of the neuropathological changes associated with diabetes mellitus, in the presence or absence of superimposed Alzheimer's Disease or vascular dementia."

###
The study was supported by grants from the National Institute of Alcoholism and Alcohol Abuse and from a COBRE award from the National Institutes of Health.

Founded in 1863, Rhode Island Hospital (www.rhodeislandhospital.org) is a private, not-for-profit hospital and is the largest teaching hospital of Brown Medical School. A major trauma center for southeastern New England, the hospital is dedicated to being on the cutting edge of medicine and research. Rhode Island Hospital ranks 13th among independent hospitals who receive funding from the National Institutes of Health, with research awards of more than $27 million annually. Many of its physicians are recognized as leaders in their respective fields of oncology, cardiology, orthopedics and minimally invasive surgery. The hospital's pediatrics wing, Hasbro Children's Hospital, has pioneered numerous procedures and is at the forefront of fetal surgery, orthopedics and pediatric neurosurgery.

Science Blog　03/16/2005

80.Those with Alzheimer's gene more likely to adjust insurance coverage

According to a new study conducted by researchers at the University of Utah, Boston University and Duke University, those who tested positive for the presence of a specific allele of the Apolipoprotein E (APOE) gene, one of the risk factors for Alzheimer's disease, were 5.76 times more likely to subsequently alter their long-term care insurance than those who did not receive the genotype disclosure.

The study, published in the March/April issue of Health Affairs, released today, revealed that almost 17 percent of the 148 healthy, cognitively normal individuals who tested positive subsequently changed their long-term care insurance coverage in the year after APOE disclosure, compared with approximately 2 percent of those who tested negative and 4 percent of those who did not receive APOE disclosure. However, there was little evidence of adverse selection in the health, life and disability insurance markets despite the fact that the sample consisted of highly motivated people, who all had a family history of Alzheimer's disease and were highly educated.

Lead author on the study, Cathleen Zick, notes, "This was not a random sample, but, rather, a sample drawn from individuals who were known to have a high degree of awareness of Alzheimer's, since one of the criteria for inclusion was that they had to have a parent or sibling with the disease." Zick, chair of the University of Utah's Department of Family and Consumer Studies and an expert on insurance behavior, points out, "The participants knew there is a genetic component to Alzheimer's, but didn't know if they had the marker. They knew that they could potentially end up with Alzheimer's and subsequently have need for long-term care. But getting the genetic information changed their interest in purchasing long-term care insurance."

The findings of the study are significant on a number of levels.

Alzheimer's disease is responsible for the longest, most common and most costly long-term insurance claims. Four and a half million Americans now have Alzheimer's, and the direct medical costs of caring for these patients are estimated to be as much as $100 billion per year. Costs are expected to rise in the future as it is estimated that 13.2 million people will have the disease by 2050.

The research is also important as genetic testing for susceptibility to adult-onset diseases like Alzheimer's -- and who should have access to genetic test results -- has sparked debate in the public policy arena.

Insurers argue that if they do not have access to such data, those who know they have an increased risk for a serious adult-onset disease and want to use the services covered by long-term care insurance, will purchase more coverage at prices that are below an actuarially fair rate. Consumers and proponents of anti-genetic discrimination legislation argue that if genetic test results are shared with insurers, many consumers could be denied coverage or charged excessively high premiums. Consumers ask "we do not choose our genes, so why should we have to pay more, or be excluded?"

In addition, the study noted, "Our findings imply that the potential for adverse selection may vary considerably by insurance market, thus making it difficult to design a public policy that works well in all instances."

Robert Cook-Deegan, one of the authors of the study notes, "The natural history of Alzheimer's disease and the power of APOE testing to predict need for long-term care combine with a private, individual long-term care insurance market to create the 'perfect storm' for adverse selection."

"Is long-term care insurance a right? Or is it an optional service some people can afford that we leave to the market?" asks Cook-Deegan, director of the Center for Genome Ethics, Law, and Policy at Duke University's Institute for Genome Sciences and Policy. "The political system is struggling to make hard choices. A federal bill banning genetic discrimination passed the Senate unanimously last year and again last month, for example, and the President is poised to sign it; but action has stalled in the House. Congress may take an important step in the right direction, but the bill does not address long-term care insurance, which may be a more imminent and pervasive threat."

Robert C. Green is a professor of neurology, genetics and epidemiology at Boston University's Schools of Medicine and Public Health, and the principal investigator on the Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study that provided the data for the current analysis. REVEAL is a randomized controlled trial evaluating the impact risk assessment with genetic disclosure for adult children of Alzheimer's patients. Green notes, "This is the first study to show that receiving genetic risk information makes a difference in the way people purchase at least one type of insurance. This is one of many ways in which clinical information from the genetic revolution is going to impact the landscape of health care and health policy in coming years."

Says Zick: "What's becoming clear is that consumers' reactions are likely to be specific to the type of genetic test and to the type of insurance in question. In the case of long-term care insurance, if policy makers decide it is a consumer's right -- then one solution is to mandate universal access to long-term care insurance. But if long term care insurance is viewed to simply be an option for protecting wealth for future generations, then, it is less clear what the government's role should be in regulating this market and the flow of information between consumers and the insurance companies."

The study was funded by grants from the National Human Genome Research Institute, the National Institute on Aging and the Alzheimer's Association. Other researchers on the project included Charles Matthews, an associate at Boston Healthcare Associates; J. Scott Roberts, assistant professor in the Department of Neurology, Boston University School of Medicine; and Robert J. Pokorski, vice president of Worldwide Medical Research and Development in Stamford, Connecticut. The Health Affairs article can be accessed online at http://content.healthaffairs.org/cgi/content/abstract/24/2/483.

From University of Utah

By BJS at 03/16/2005 - 05:50 | business & economy | login or register to post comments | printer friendly page

Copyright 2005, Science Blog.

03 April 2005　www.sundayherald.com

81.Global study reveals algae in world’s water is causing Alzheimer’s disease

By Rob Edwards, Environment Editor

A HIGHLY toxic acid that could cause degenerative brain diseases such as Alzheimer’s has been discovered in the algal blooms that plague waters in Scotland and around the world.
Scientists fear that the spread of “blue-green” algae across lochs and seas, caused by pollution, is now putting human health at risk. There is “a potential for widespread human exposure” to the toxin in the algae, they warn.

Algal blooms in Scotland are known to be fed by discharges from sewers, and some of them have proved toxic to fish, shellfish and pets. But until now they have never been linked to the occurrence of brain disease in humans.

Now an international team of researchers, including three from the University of Dundee, have detected a neurotoxin in 29 out of the 30 samples of blue-green algae they have tested. The samples were taken from a variety of water sources in Scotland, Northern Ireland, the Netherlands, Israel, India, Australia, the US and elsewhere.

The toxin is a naturally occurring amino acid known as beta-methyl-amino-alanine, or BMAA for short. It has been blamed for causing a high incidence of a disease similar to Alzheimer’s amongst the Chamorro people on the island of Guam in the Pacific.

BMAA has also been found in the brain tissue of Alzheimer’s patients in Canada, suggesting it may have caused the disease. Although the way in which toxins in algal blooms could infect humans is still unclear, scientists stress that precautions should be taken now, particularly with our drinking water supplies.

“We now know that BMAA is widely produced by cyanobacteria (blue-green algae) from throughout the world,” said Professor Geoffrey Codd, one of the researchers from the School of Life Sciences at Dundee University.

“This indicates that human exposure to BMAA may also occur more widely and that BMAA should be monitored in water resources, including reservoirs, if they contain cyanobacteria.

“Now that we know about BMAA in cyanobacteria, steps can be taken to reduce the risks to health which the substance may present.”

According to Codd, this is the first time that such a toxin has been found to be so widespread amongst algal blooms. “Samples of cyanobacteria were collected from fresh-waters, seas, soil, lichen, a cave and a hot spring from across the world. Of a sample of 30 cultures, 95% of them were shown to produce BMAA,” said Codd.

The finding was “of ecological and evolutionary significance”, he suggested. There was no doubt that BMAA was “neurotoxic”, but its precise links with human neurological diseases were “uncertain”.

BMAA has previously been discovered in the roots of ancient palm-like plants known as cycads. On Guam, it concentrates in the flying foxes that feed on cycads, and then in the Chamorro people who eat the flying foxes.

BMAA has been found in the brains of Chamorro people who have died from a paralytic dementia known as ALS/PDC, but not in those who have died from other causes. The acid binds to proteins in the body and is released over years, causing it to be branded as a “slow toxin”.

But in 2003, when BMAA was detected in the brains of nine Canadian Alzheimer’s patients, scientists started suspecting that it might have come from blue-green algae. So they decided to analyse as much algae as they could from around the planet.

The results will be published tomorrow in the Proceedings of the National Academy of Sciences of the USA. Along with Codd, Dr James Metcalf and Louise Morrison from Dundee University, the research team includes experts from institutes in Hawaii, California and Sweden.

“We were surprised to find that BMAA is produced by such a diversity of cyanobacteria throughout the world,” said research leader, Paul Alan Cox, from Hawaii’s Institute for Ethnomedicine at the National Tropical Botanical Garden.

Algal blooms are a natural phenomenon, but their frequency and extent are being boosted by pollution. Their growth is enhanced by phosphates from sewage, detergents, fertilisers and fish farms, as well as by the global warming caused by greenhouse gases like carbon dioxide.

Environmental groups pointed out that some efforts were already being made by industry and regulators to reduce the pollution that feeds algal blooms in lochs. But much more needed to be done, they argued.

“Algal blooms were a serious enough problem already. Now that there is a possible link to human brain problems, we should redouble our efforts to reduce the pollution which helps them occur,” said Mike Donaghy, freshwater policy officer with the environmental group, WWF Scotland.

“More toxic algae is another nasty little side effect of climate change .”

The Scottish Environment Protection Agency, the government’s green watchdog, was unable to comment on the new research last week.

April 13, 2005, the Milwaukee Journal Sentinel

82.An improved state of mind-Antibodies may help Alzheimer's patients-
By JOHN FAUBER

Miami Beach - The mental skills of a small group of Alzheimer's patients improved after antibodies derived from human plasma were infused directly into their blood, according to a promising new study.
The researchers said they were hoping just to stabilize the patients.
"Much to our surprise, the patients showed clear signs of improvement," said co-author Norman Relkin. "Some of them started telling stories again. They started socializing again."
Because the study involved just eight patients, at this point the treatment can be considered only promising, according to Alzheimer's researchers not associated with the study.
"This is still quite far from a potential treatment," said Sanjay Asthana, head of geriatrics at the University of Wisconsin Medical School in Madison. "There is great promise in terms of the science, but this study is very, very early."
A potential benefit to the new treatment is that it uses a blood product that has been around for 30 years and that has an established safety record, said Piero Antuono, an Alzheimer's specialist at the Medical College of Wisconsin and Froedtert Memorial Lutheran Hospital.
"The results look promising, and the tool that they are using is not high science," Antuono said.
Encouraged by the results, researchers are planning two larger trials, one of which is scheduled to begin this year.
The treatment, which was presented at the American Academy of Neurology annual meeting here, is one of several experimental therapies under way that target beta-amyloid, the protein that accumulates in the brain of Alzheimer's patients and that is believed to cause brain cells to die.
New approach, old idea
The new approach is similar to other so-called Alzheimer's vaccines, in that it relies on antibodies to target amyloid-beta.
An earlier trial of an active vaccine that stimulated the immune systems of patients to produce their own amyloid-beta antibodies was stopped in 2002 when 15 patients developed severe swelling in the brain.
The new approach uses a form of passive immunization in which existing antibodies are infused into the blood at various times, anywhere from once a week to once a month.
The trial was funded primarily by Baxter Bioscience, which makes the plasma product that was studied, along with support from several other organizations, including the National Institutes of Health and the Alzheimer's Association.
The trial was started after Relkin and others reported in 2002 that Alzheimer's patients had three times fewer antibodies to amyloid-beta.
They tried intravenous immunoglobulin (IVIg), an antibody product that has been safely used for decades to treat immune system conditions in hundreds of thousands of patients, said Relkin, director of the memory disorders program at New York-Presbyterian / Weill Cornell Medical Center.
It is believed that IVIg binds to amyloid-beta, making it more difficult for the protein to clump around brain cells.
In addition to increasing levels of both amyloid-beta antibodies and amyloid-beta in the blood, researchers reported that levels of amyloid-beta decreased in cerebrospinal fluid of the patients, a sign that the antibodies were decreasing amyloid-beta in the brain.
The treatment is a relatively simple approach, said Sam Gandy, a spokesman for the Alzheimer's Association.
"It's an interesting thing to try while we are going on with much more sophisticated strategies," said Gandy, also director of the Farber Institute for Neurosciences at Thomas Jefferson University, who was not involved with the study.
For the study, eight people with mild to moderate Alzheimer's were treated with various doses of IVIg.
Over the course of six months, seven of the patients underwent cognitive testing.
Cognitive decline stopped in all seven patients who had undergone testing and improved in six.
In addition to needing to replicate the results in a larger group of patients, the researchers will need to image the brains of the patients to see if beta-amyloid plaques in the brain actually are decreasing, Gandy said.
Although IVIg is widely available, it costs about $3,000 to $7,000 a month, Relkin said.
And even though it is approved for other uses, he said Alzheimer's patients should not be put on the drug.
A limited amount of the drug is produced and a surge in use by Alzheimer's patients could result in people with other diseases being deprived of the medicine, he said.

83.Pessimism raises dementia risk, study finds
14 Apr 2005 22:01:25 GMT Alertnet Source: Reuters

WASHINGTON, April 14 (Reuters) - Pessimistic, anxious and depressed people may have a higher risk of dementia, U.S. researchers reported on Thursday.
A study of a group of 3,500 people showed that those who scored high for pessimism on a standardized personality test had a 30 percent increased risk of developing dementia 30 to 40 years later.
Those scoring very high on both anxiety and pessimism scales had a 40 percent higher risk, the study showed.
"There appears to be a dose-response pattern, i.e., the higher the scores, the higher the risk of dementia," Dr. Yonas Geda, a neuropsychiatrist at the Mayo Clinic in Rochester, Minnesota who led the study, said in a statement.
Geda and colleagues looked at the medical records of 3,500 men and women who lived near the clinic between 1962 and 1965.
They all took the Minnesota Multiphasic Personality Inventory, a standard personality and life experience test, Geda's team told a meeting of the American Academy of Neurology in Miami.
In 2004 the team interviewed the participants or family members.
Those who scored higher for anxiety and pessimism on the test were more likely, as a group, to have developed dementia by 2004, including Alzheimer's disease and vascular dementia.
This did not mean a person who is pessimistic could assume he or she has a higher risk of developing dementia.
"One has to be cautious in interpreting a study like this," Geda said.
"One cannot make a leap from group level data to the individual. Certainly the last thing you want to do is to say, 'Well, I am a pessimist; thus, I am doomed to develop dementia 20 or 30 years later,' because this may end up becoming a self-fulfilling prophecy."
And there is not any specific way to prevent dementia, although many studies have shown that a healthy diet, exercise, keeping active in other ways, doing puzzles and other activities lower the risk.

Alzheimer's Association

84.Nationwide study of new Alzheimer drug
April 19, 2005

Astellas Pharma U.S. has launched a nationwide clinical trial of FK962, an experimental drug for the treatment of Alzheimer’s disease. FK962 appears to trigger the release of somatostatin (soh mat uh STAT in) in regions of the brain important in learning and memory.

The trial is designed to test whether stimulating release of somatostatin with different doses of FK962 is safe and may help individuals with mild to moderate Alzheimer’s. The study will enroll 510 participants at sites throughout the United States and Canada. Enrollees will receive one of five oral doses of FK962 or a placebo (inactive treatment) for 24 weeks. Medication will be given to each participant’s caregiver with instructions on when and how to administer it.

Participants and caregivers will be required to make at least 6 visits to their study site over 26 weeks. Other requirements include the following:

Participants must not have taken other Alzheimer medications within six weeks of being screened for this study

Use of certain other medications is also restricted

At least six blood samples and certain other laboratory tests will be required

Somatostatin is a hormone produced in a number of tissues throughout the body. Its primary role is to block release of other hormones. In the brain it also functions as a neurotransmitter, a specialized messenger chemical that carries information from one nerve cell to another.

Scientists have found that Alzheimer’s disease is associated with reduced brain levels of several neurotransmitters, including somatostatin. Laboratory animal research has shown that interfering with somatostatin signaling may cause memory problems and that administering the hormone may benefit memory. In addition, a small human study suggested that somatostatin improved memory for individuals with Alzheimer’s disease.

For more details about the study and a list of U.S. and Canadian sites, please visit the National Institute on Aging (NIA) clinical trial index (http://www.alzheimers.org/clintrials/fullrec.asp?PrimaryKey=197). The toll-free information line for the study is through the Astellas Medical Information Department at 800.727.7003.

For additional background information, please see:

An abstract of a review article by Gennaro Schettini, M.D., in the April 23, 1991, issue of Pharmacological Research, discussing the normal role of somatostatin in the brain and its impaired function in Alzheimer’s disease

An abstract An abstract of the small human study by Suzanne Craft, Ph.D., and colleagues, reported in the Dec. 1999 Archives of General Psychiatry, showing a potential benefit of somatostatin in treating Alzheimer’s

General information on somatostatin from Colorado State University

Alzheimer’s Association

85.FDA issues advisory on atypical antipsychotics
April 19, 2005

The U.S. Food and Drug Administration (FDA) today issued a public health advisory on the use of a class of drugs called “atypical antipsychotics” to treat agitation, aggression, hallucinations, delusions and other behavioral and psychiatric symptoms of Alzheimer’s disease. The purpose of the advisory is to alert health care professionals and consumers that taking these drugs is associated with an increased risk of death for individuals with dementia. This conclusion is based on FDA’s analysis of 17 studies, which showed that those taking the drugs had an increased death rate compared with those taking a placebo (inactive treatment).

Alzheimer’s Association science advisors familiar with the data say that the number of deaths in the placebo group was about one percent of participants and the number in the group receiving atypical antipsychotic drugs was between one-and-one-half and two percent. The analysis has not yet been published.

Although the deaths were from various causes, many appeared to be heart-related or due to pneumonia or other infections.

FDA is requiring manufacturers of all drugs of this type to add a “black box” warning to their products alerting the public of the increased death risk. The boxed warning must also note that none of these drugs is approved by FDA to treat dementia symptoms. In addition, FDA advises any patients with dementia currently receiving these drugs to have their treatment reviewed by their physician.

Atypical antipsychotic drugs covered by FDA’s advisory include:

olanzapine (Zyprexa)
aripiprazole (Abilify)
risperidone (Risperdal)
quetiapine (Seroquel)
clozapine (Clozaril)
ziprasidone (Geodon)
olanzapine/fluoxetine (Symbyax)

These drugs are approved by FDA to treat symptoms of schizophrenia and bipolar disorder (manic depression).

Alzheimer’s Association science staff and advisors offer the following observations on the FDA action and the use of these drugs to treat behavioral and psychiatric symptoms of dementia.

About the FDA action:
The increased risk of death revealed by the analysis is “real but small” and should become part of a complete and thoughtful benefit/risk discussion about use of these drugs involving the physician, the family and the individual with dementia. These drugs are also associated with other potentially serious side effects that should be considered in the risk/benefit discussion.
Although none of these drugs has ever been specifically approved to treat behavioral and psychiatric dementia symptoms, mainstream clinical consensus is that there are times when their use for this purpose is an important and appropriate option for physicians to consider.

About behavioral and psychiatric Alzheimer symptoms:
Behavioral and psychiatric problems eventually affect many individuals with Alzheimer’s. These symptoms are associated with the later stages of the disease and are often a signal of rapid decline. They cause profound distress to individuals with the disease and may put them at risk of injury.
These symptoms can also create difficult situations for family caregivers and are often a determining factor in deciding to place the diagnosed individual in residential care.
Behavioral symptoms can also have a negative effect on care and quality of life for those living in long-term care facilities.
It is important whenever possible to identify correctable factors that may trigger behavioral symptoms, such as urinary tract or other underlying infections, constipation, pain, or environmental discomforts (temperature extremes, insufficient light, loud noise).
When the physician, family and individual with dementia or the surrogate medical decision-maker agree that trying a drug treatment is an appropriate next step, atypical antipsychotics are the drugs that have been most extensively studied for this purpose.
Most studies have shown that the antipsychotic drugs are modestly effective at treating these symptoms. These drugs may not help all individuals and may help some more than others.
An individual taking antipsychotic drugs should be carefully monitored for response to treatment and side effects.
These drugs should not be overused and ongoing need for the drug should be carefully evaluated.
Research in this area remains ongoing. A large clinical trial funded by the National Institute of Mental Health (NIMH) is comparing the effectiveness of three atypical antipsychotics and one antidepressant in treating behavioral and psychiatric symptoms of dementia. This trial is Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).
Through its own research program, advocacy for greater public funding and collaborative relationships with pharmaceutical companies, the Alzheimer’s Association strongly supports the effort to develop safer, more effective treatments for Alzheimer’s disease as well as preventive strategies.

For more information, please see:
FDA’s "Talk Paper" on today’s public health advisory
http://www.fda.gov/

FDA’s public health advisory
http://www.fda.gov/

FDA’s information page on atypical antipsychotic drugs, including health care professional sheets (consumer information sheets are still under development)
http://www.fda.gov/

Alzheimer’s Association fact sheet on behavioral and psychiatric symptoms of dementia
http://www.alz.org/

Apr 25, 2005 Health - AP

86.Gene Therapy May Hold Back Alzheimer's

By LAURAN NEERGAARD, AP Medical Writer

WASHINGTON - The first attempt at gene therapy for Alzheimer's patients appeared to significantly delay worsening of the disease in a few people who have tested it so far, scientists reported Sunday.
Far more research is needed to see if the experimental treatment, which requires a form of brain surgery, really helps.
But if the approach pans out, researchers say delivering protective substances, called growth factors, into a diseased brain holds the potential to rescue some dying brain cells.
In one patient, the brain tissue showed new growth, which was a first, according to a study published in Sunday's edition of the journal Nature Medicine.
"It won't cure the disease," said the lead researcher, Dr. Mark Tuszynski of the University of California, San Diego. That is because Alzheimer's destroys different types of cells in different areas of the brain; the new gene therapy targets just one of those.
The preliminary success indicates that similar approaches might help other neurodegenerative diseases, such as Parkinson's, Tuszynski said. "This is in a sense proof of principle for the potential use of growth factors," he said.
Doctors at Chicago's Rush University Medical Center have begun a second small study of the approach in Alzheimer's patients. Tuszynski, who co-founded a biotechnology company that is funding the Chicago work, hopes larger studies will begin within another year.
Tuszynski and colleagues took skin cells from eight patients in the early stages of Alzheimer's and modified the genes to secrete a protein found in healthy brains called nerve growth factor, or NGF.
Earlier studies had shown that injecting NGF-producing tissue into the brains of aging monkeys could reverse deterioration. Simply injecting NGF into people would not work. If it goes into the wrong part of the brain, it can cause serious side effects.
So, doctors drilled holes into the patients' skulls and implanted the NGF-producing skin cells directly onto Alzheimer's-injured spots.
Six patients were tracked for almost two years. Tests involving memory and other skills found their rate of cognitive decline slowed by 36 percent to 51 percent, better than is usually seen with medication, Tuszynski reported.
The first two patients were awake and moved during the cell implantation, causing bleeding in their brains; one patient died five weeks later. Remaining patients received the implants under general anesthesia to keep them still, and the researchers reported no further problems.
The brain tissue of the study participant who died had new growth protruding from Alzheimer's-injured cells at the implant site, the first time that sort of recovery has been seen from a human brain treatment, Tuszynski said. Additionally, PET scans of the other participants showed a measurable increase in their brains' metabolic activity.
"These results need to be interpreted with cautious optimism," said William Thies of the Alzheimer's Association. With so few patients in the study, "it's really impossible to tell whether the benefit was due to the treatment or natural fluctuation in symptoms," he said.
Moreover, he said, it would never be practical to perform brain surgery on millions of patients. Already, 4.5 million Americans have Alzheimer's, and with the country's population aging, a staggering 14 million may have it by 2050.
But if the gene-therapy approach ultimately works, it could revive interest in finding easier methods, he said.
As for the next step, instead of genetically modifying skin cells, Dr. David Bennett of the Rush University Medical Center has begun injecting the brains of up to 12 Alzheimer's patients with an NGF-bearing virus.
Animal studies suggest the virus may penetrate injured brain cells better, producing more of the protective growth factor for longer periods, he said.
"It's cautious optimism with a big C," Bennett stressed. "It can't be a cure, obviously ... but maybe it'll do something."

The Courier　25 April 2005　　http://www.thecourier.co.uk

87.Success of dementia pilot scheme
AN ANGUS pilot project to support people in the early stages of dementia has achieved significant success.

Established last year as part of the work of the community mental health teams, which are a joint Angus Council/Angus NHS Trust initiative, the dementia project gives people recently diagnosed and their carers information, advice and support at an early stage in the illness.

Feedback has revealed that in almost every case the offer of support and a friendly ear has been a major benefit for those diagnosed with dementia and the success has ensured a wider roll-out of the programme with an extended remit to cater for the needs of young adults.

Angus social work committee heard last week that 96% of the people referred to the new service said being able to discuss things with the early dementia services worker had greatly helped them to address their concerns, a view shared by all of their carers.

“This pilot provides emotional and practical support as well as access to appropriate resources for service users recently diagnosed with dementia and their carers,” said social work director Dr Robert Peat.

“The project is designed to provide a collaborative approach with partner agencies such as health, housing and the voluntary sector.”

Angus Council social work and health convener Glennis Middleton said the success of the pilot project clearly demonstrated the value of early intervention to meet the needs of people diagnosed as having early stage dementia.

“Living with any illness is difficult. Learning to live with an illness with no visible physical disability, but where sufferers may be behaving inconsistently and have problems communicating, can be very hard,” she said.

In all 72 referrals were made to the service in 2004 and, in addition to providing detailed information about dementia, the early dementia services co-ordinator also assisted with practical matters such as claiming allowances (22 applications for attendance allowance were successfully processed amounting to ?40,924) and other matters such as welfare and power of attorney.

“The pilot scheme has proved to be an invaluable support for both service users and their carers so our intention now is to continue to work with other agencies such as Alzheimer Scotland to raise awareness of the service and to develop support services across the region,” added Mrs Middleton.

Brechin councillor Joy Mowatt added, “I was very encouraged by this report on the early stage dementia project. For anyone in the early stages of dementia, and those caring for them, it is a helping-hand project and it must give great comfort and re-assurance to them at a time when there will be a lot of anxiety.”

Myriad Genetics News Release - 2-May-2005

88.Myriad Genetics Reports Results of Phase 2 Trial of Flurizan(TM) in Patients With Alzheimer's Disease

- Conference Call Scheduled for 4:00 p.m. Eastern Time Today -
SALT LAKE CITY, May 2, 2005 /PRNewswire-FirstCall via COMTEX/ -- Myriad Genetics, Inc. (Nasdaq: MYGN), announced that preliminary results of its Phase 2 clinical trial of Flurizan did not achieve statistical significance in patients with mild to moderate Alzheimer's disease; however, a positive trend was observed on all three primary endpoints in patients with mild Alzheimer's disease, on the 800 mg twice-daily dose. Additionally, mild Alzheimer's disease patients who achieved high plasma concentrations of Flurizan demonstrated a statistically significant effect in two of the three primary endpoints. The initial findings also indicate that Flurizan was well tolerated in this 12-month, 207 patient clinical study.

The three primary endpoints of the Phase 2 study were the Alzheimer's Disease Cooperative Study -- Activities of Daily Living inventory (ADCS-ADL), Clinical Dementia Rating -- Sum of Boxes (CDR-sb), and the Alzheimer's Disease Assessment Scale -- Cognitive function subscale (ADAS-cog). Patients with mild Alzheimer's disease who were given the 800 mg twice-daily dose of Flurizan demonstrated a 44% slowing of decline in their performance of activities of daily living, as measured by the ADCS-ADL. This assessment measures basic activities of daily living such as dressing and eating.

The 800 mg twice-daily drug-treated group with mild disease at baseline demonstrated a 41% slowing of decline during the 12-month study period in global function as measured by the CDR-sb. In this exam, the investigator performs a semi-structured interview with both the patient and the caregiver. The patient's performance is assessed in memory, orientation, judgment, problem solving, community activities, home and hobbies and personal care.

A positive trend was also seen in patients with mild disease on the 800 mg twice-daily dose for the primary cognitive endpoint, ADAS-cog. This group achieved a 29% slowing of cognitive decline. The ADAS-cog measures a patient's performance in word recall, response to directions, ability to copy geometric forms, delayed word recall, ability to name objects, memory and quality of speech.

A further analysis of data from 128 mild Alzheimer's disease patients (68% of the patients eligible for analysis) indicates that those who achieved the greatest plasma concentrations of Flurizan demonstrated a statistically significant 67% reduction in decline in activities of daily living (p=0.017, two-sided) as measured by ADCS-ADL, compared to patients in the placebo group. This finding was confirmed by analyzing the same group of patients versus the control group for the global function assessment, which showed a 54% slower decline (p=0.034, two-sided) as measured by CDR-sb. Finally, the high plasma concentration group demonstrated a 30% slowing in the rate of decline of cognitive function (not statistically significant), as measured by ADAS-cog.

"This study has been very useful and indicates that this drug may well be helpful in early stages of Alzheimer's disease," said Gordon Wilcock, M.D., Professor in Care of the Elderly, University of Bristol, United Kingdom. "It is in keeping with the evolving understanding of the relationship between amyloid deposition and Alzheimer's disease. The study has also shown a dose that is most likely to be effective. We now need further studies to confirm these findings."

In addition to efficacy measures, the Phase 2 trial assessed the safety of Flurizan in the study population. The preliminary results showed that Flurizan was well tolerated in this study. Review of the full safety data set is underway.

"Even though Flurizan did not achieve significance in the primary endpoints of the Phase 2 Alzheimer's study, we are encouraged by the statistically significant effect observed in the mild Alzheimer's disease patients, " said Peter Meldrum, President of Myriad Genetics, Inc.

Based on the Phase 2 results, the Company intends to continue its Phase 3 trial, and believes that 800 mg twice daily is the preferred dose. The Company will review the protocol for the Phase 3 study with the principal investigators to determine any modifications in treatment regimens. Subject to regulatory approval, the Company will also consider modifying the Phase 3 protocol to focus future enrollment on mild Alzheimer's disease patients. Additionally, the Company will continue to analyze the data from the moderate Alzheimer's disease patients in order to better understand the effect of Flurizan in this population.

The Phase 2 trial was conducted at approximately 30 centers in the United Kingdom and Canada, with 189 patients who qualified for the intent-to-treat analysis. It was designed to study the safety and efficacy of Flurizan in altering the progression of Alzheimer's disease. The format of the trial was double blind and placebo-controlled, with a 12-month study period. Patients were randomized into one of three groups upon enrollment in the trial, and given twice-daily doses of either 400mg or 800mg of drug or placebo. At the time of enrollment, the patient group as a whole had an average Mini Mental State Exam (MMSE) score of 21 and the trial was composed of 50% men and 50% women.

About Flurizan

Flurizan is a selective amyloid beta 42 lowering agent (SALA). Flurizan has been shown to be effective in lowering levels of Abeta42 in cellular assays and animal models. Abeta42 is the primary constituent of senile plaques that accumulate in the brains of patients with Alzheimer's disease. It is thought to be the key initiator of Alzheimer's disease since this peptide has the greatest tendency to aggregate, cause neuronal damage and initiate amyloid deposits in the brain. Most genetic mutations that cause early-onset Alzheimer's disease appear to do so by increasing production of Abeta42. Myriad believes that Flurizan is the first well-tolerated drug that inhibits the production of Abeta42 to be evaluated in a clinical trial for the treatment of Alzheimer's disease.

Conference Call and Audio Web Cast

Myriad management will host a conference call at 4:00 p.m. Eastern time today, May 2, 2005, to discuss today's announcement. The call-in number for the conference call will be (888) 589-2820 or (706) 634-2173. A replay of the conference call will be available for one week following the call by dialing (800) 642-1687 or (706) 645-9291, and entering conference identification number 6051295. The call will also be available through a link on Myriad's home page at www.myriad.com.

About Myriad

Myriad Genetics, Inc. is a biopharmaceutical company focused on the development of novel healthcare products. The Company develops and markets predictive medicine products, and is developing and intends to market therapeutic products. Myriad's news and other information are available on the Company's Web site at www.myriad.com.

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward looking statements include, the positive trend observed on all three primary end points in patients with mild Alzheimer's disease on the 800 mg twice daily dose; Flurizan's demonstrated statistically significant effects in two of the three primary endpoints; the positive trend seen in patients with mild disease on the 800 mg twice daily dose for the primary cognitive endpoint, ADAS-cog; the statistically significant reduction of 67% in the decline in activities of daily living (p=0.017, two sided) as measured by ADCS-ADL in patients who achieved the greatest plasma concentrations of Flurizan as compared to patients in the placebo group; the encouragement of the Company with respect to the statistically significant effect observed in the mild Alzheimer's disease patients; the toleration of Flurizan by study patients; the continuation of the Company's Phase 3 trial; the Company's belief that 800 mg twice daily is the preferred dose; the Company's review of the Phase 3 study to determine modifications of the treatment regimes; the modification the Phase 3 protocol to focus future enrollment on mild Alzheimer's disease patients; the Company's continued study and analysis of the data from the moderate Alzheimer's disease patients; and the ability of Flurizan to be helpful in early stages of Alzheimer's disease. The forward-looking statements are based on management's current expectation and are subject to certain risks and uncertainties that could cause actual results to differ materially from those set forth or implied by forward-looking statements. These include, but are not limited to, uncertainties related to the clinical development of drugs, including that results in earlier stage clinical trials will not be repeated or confirmed in larger, later stage studies; uncertainties as to the extent of future government regulation of Myriad Genetics' business; uncertainties as to whether Myriad Genetics and its collaborators will be successful in developing, and obtaining regulatory approval for, and commercial acceptance of, therapeutic compounds; the risk that markets will not exist for therapeutic compounds that Myriad Genetics develops or if such markets exist, that Myriad Genetics will not be able to sell compounds, which it develops, at acceptable prices; and the risk that the Company will not be able to sustain revenue growth for its predictive medicine business and products. These and other risks are identified in the Company's filings with the Securities and Exchange Commission, including the Company's Annual Report on Form 10-K for the fiscal year ended June 30, 2004. All information in this press release is as of May 2, 2005, and Myriad undertakes no duty to update this information unless required by law.

SOURCE Myriad Genetics, Inc.
William A. Hockett, Vice President of Corporate Communications, of, Myriad Genetics, Inc., +1-801-584-3600, bhockett@myriad.com

WebMD Medical News April 13, 2005

89.Religion, Spirituality May Slow Alzheimer's Slower Rates of Mental Decline Cited in Small Study

Reviewed by Michael Smith, MD

April 13, 2005 -- Religious practices and spirituality may slow the progression of Alzheimer's disease.
The study is the first to look at religion, spirituality, and Alzheimer's disease, researcher Yakir Kaufman, MD, tells WebMD.
"There are many studies showing the relationship between spirituality and religiosity and other disease outcomes," Kaufman says. "Lately, there have also been a few [suggesting] a relationship between spirituality, religion, and neurological disease."
But the preliminary findings come from a small study and need confirmation, say Kaufman and co-researcher Morris Freedman, MD.
"This must not be overinterpreted; this is only one study," says Freedman, head of neurology and director of the behavioral neurology program at Toronto's Baycrest Centre for Geriatric Care.

Religions Slows Mental Decline
The researchers saw a slower rate of mental decline in Alzheimer's patients with higher levels of religion and spirituality. The researchers presented their findings at the American Academy of Neurology's annual meeting in Miami Beach, Fla.
Kaufman and colleagues used two scales of religion and spirituality. One scale had five items covering religious attendance, private religious practices, and intrinsic religiosity (experiences of the divine and the influence of religious beliefs in daily life). The other scale asked participants to rate their personal level of religiosity or spirituality.

Faith Findings
Participants were 68 Alzheimer's patients who were about 78 years old, on average. Most had mild cases of Alzheimer's disease. The group included a mix of ethnicities and backgrounds, with Christians, Jews, a Buddhist, and an atheist, says Kaufman.
Patients were followed for an average of three years. Their scores on mental and neurological tests were noted, showing the disease's progression.
Higher levels of religiosity and spirituality were associated with a slower progression of Alzheimer's disease.
Kaufman worked on the study while on staff at Toronto's Baycrest Centre for Geriatric Care. Now, he is the director of neurological services at Sarah Herzog Hospital in Jerusalem.

Finding 'Not Unexpected'
The study's results are "interesting, and not unexpected, actually," says Harold G. Koenig, MD, MHSc, a Duke University professor of psychiatry and associate professor of medicine. Koenig has done extensive research on religion and mental health, but he wasn't involved in this particular project.
Koenig tells WebMD that religion doesn't guarantee health, but that it can bring "comfort, hope, meaning, and purpose," along with support from faith-based communities. That could help religious people cope with stress, illness, or depression, which might reduce their risk of Alzheimer's disease, says Koenig.
General trends don't always apply to everyone, he notes. "You can't conclude every case is going to be like this." Positive mental traits aren't unique to people who consider themselves spiritual, he adds.
Illness can strike anyone and should not be seen as a shortfall of the spirit. "There [are] plenty of ministers that have experienced Alzheimer's," says Koenig. "You can't conclude the opposite from these studies. That's just not the case all the time."

About Alzheimer's Disease
In the U.S., an estimated 4.5 million people have Alzheimer's disease, says the Alzheimer's Association. The progressive brain disease damages parts of the brain involved in memory, intelligence, judgment, language, and behavior.
Alzheimer's disease becomes more common with age. It affects one in 65 U.S. adults older than 65 and nearly half of those older than 85, says the Alzheimer's Association.

57th Annual Meeting of the American Academy of Neurology, Miami Beach, Fla., April 9-16, 2005. Yakir Kaufman, MD, director, neurology services, Sarah Herzog Hospital. Morris Freedman, MD, head, neurology; director, behavioral neurology program, Baycrest Centre for Geriatric Care. Harold G. Koenig, MD, professor of psychiatry and behavioral medicine, associate professor of medicine, Duke University. News release, American Academy of Neurology. Alzheimer's Association. WebMD Medical Reference from Healthwise: "Alzheimer's Disease: Topic Overview."

May 04, 2005　www.israel21c.org

90.Israeli research provides insight into formation of lasting memory
By Rava Eleasari

When we experience a friendly encounter, a new taste or a mental leap, how is it that sometimes these events are imprinted on our minds forever, while other daily occurrences fade into nothingness? The riddle of long-term memory formation has come one step closer to being solved due to a discovery in Israel by Tel Aviv University biochemist Dr. Malka Cohen-Armon of the Sackler Faculty of Medicine
Cohen Armon, in collaboration with scientists at Bar-Ilan University and Columbia University in the US, found that a protein called PARP1, present in the nucleus of cells in animals and plants, is rapidly activated in brain cells in response to external stimulation and allows the formation of lasting memories.
PARP1 itself is not a new discovery; for 40 years, scientists have known that activation of this protein is an early emergency response of cells to stress conditions that can damage the genetic information stored in DNA. These stress conditions include cell aging, injury, inflammation or exposure to radiation. Activation of PARP1 rapidly releases the proteins surrounding the DNA molecule, enabling access to the damaged sites and making it possible for repairs to be made.
Cohen-Armon and her partners discovered a second function of PARP1, unrelated to stress conditions. They showed that activation of the protein is essential to the expression of genes that govern the formation of long-term memory.
"Short-term memory and long-term memory involve different processes," explains Cohen-Armon. "With short-term memory, no gene transcription is required. Long-term memory formation, however, entails the expression of specific genes."
PARP1 activation enables these genes to go into action.
"Picture the shutter of a camera," says Cohen-Armon. "The shutter protects the film in the camera, except that in our case that film is the DNA molecule in a cell's nucleus, and the shutter is made up of proteins surrounding the DNA. Ordinarily, PARP1 activation opens that shutter to allow repair procedures to breaks in the DNA. We found that this same shutter mechanism opens access to DNA during the learning process, enabling the DNA transcription specific to long-term memorization to occur."
The researchers tested their theory on the sea slug, Aplysia californica, whose primitive nervous system has been used for three decades as a model for basic functioning of the brain. In training the slug to ignore inedible food, the researchers noted that PARP1 was activated in its nervous system, and that this activation was essential for the slug?s ability to remember this learning task over the long term. Moreover, long-term memory was completely prevented by inhibiting PARP1 activity.
The findings, which were published in Science, highlight a novel mechanism in the pattern of memory formation that may have implications for treating diseases such as Alzheimer?s and Parkinson's, mental illness, and other conditions that involve memory or concentration impairment.
(Originally appeared in Tel Aviv University News)
Rava Eleasari is Head of Publications at Tel Aviv University.

BMJ 2005;330:1041 (7 May) News

91.Dutch approve euthanasia for a patient with Alzheimer's disease

Tony Sheldon
Utrecht
The Netherlands' first reported case of a doctor complying with a request for assisted suicide from a patient with Alzheimer's disease was lawful, a report has said.
The case was reported to the Netherlands' assessment committee system, which consists of five regional committees and checks whether doctors have followed the requirements of the law. If members of the relevant committee judge that the legal requirements have been met, they do not forward the case to the public prosecution service.
Committee members have defended their decision, maintaining that approval for the case did not show that the country was on a "slippery slope" towards a general acceptance of euthanasia for cases of Alzheimer's disease.
The case emerged in the 2004 annual report of the five committees of doctors, lawyers, and ethicists to whom doctors must report euthanasia. The committees judged that four out of 1886 cases of euthanasia and assisted suicide in 2004 failed the legal requirements, and, as the law requires, forwarded these to the public prosecution service.
But, in contrast, the case of a patient with Alzheimer's disease was considered to have met requirements as a "well-considered and voluntary request" to die. The patient was also considered to be "suffering hopelessly and unbearably," which is another of the criteria that makes euthanasia lawful.
The committees' report states that, in general, patients with Alzheimer's disease could not always comply with the requirements but that "in specific circumstances" they could. The 65 year old patient had had Alzheimer's disease for three years. Since his diagnosis he had said that he did not wish to endure the full course of his illness and had in the previous year repeatedly asked for help to commit suicide.
The doctor judged him to be suffering unbearably. He was conscious that he could no longer function independently and faced the future prospect of increasing dementia.
A second opinion from a doctor trained through the national support and consultation with euthanasia programme, however, did not recognise such suffering. This doctor argued that the patient's awareness of his suffering would decline as the disease progressed and doubted that the patient was competent to express his wishes.
Further consultations with a psychologist, a nursing home doctor, and a gerontopsychiatrist, however, all concluded that the patient was suffering unbearably because he was conscious that the disease was removing control over his life. They believed too that he remained competent.

Genetic Engineering News　 5/11/2005

92.GW Medical Technologies' New Blood Test for Alzheimer's Disease Seeks Future Test Candidates; Patients and Physicians Needed for Breakthrough Test

GW Medical Technologies LLC, the worldwide technology provider of the blood test for Alzheimer's disease (AD) known as the LymPro(TM) Test, announces a nationwide online registration of Alzheimer's patients, caregivers and physicians who want to become involved in upcoming clinical studies for this breakthrough diagnostic blood test for Alzheimer's disease.
Those individuals who are interested in participating in future clinical studies can register by going to the company Web site at www.GWmedtech.com. The online registration takes less than one minute to complete. As new clinical studies are launched, those who sign up as interested parties will be contacted first with complete study details and requirements. These studies will be part of the FDA Pre-market Approval (PMA) process for the LymPro Test, which the company is planning to submit to the FDA within the near future.
Additionally, the Web site includes a confidential survey for AD patients, caregivers and physicians to express their attitudes and opinions about the current diagnostic process for Alzheimer's disease. The survey responses will be used to create educational programs explaining how the LymPro Test works and the benefits it provides.
"Bringing this diagnostic blood test for Alzheimer's to market as soon as possible is critical to accelerating treatment options and improving quality of life for thousands of patients and their families who are enduring the current lengthy diagnostic process," said William Gartner, CEO and president of GW Medical Technologies LLC.
The company is in the final phase of its retrospective "blind" pilot study with samples from healthy participants, those with Alzheimer's disease, as well as those with other forms of dementia. This study has been designed to enhance the method prior to undertaking final FDA clinical studies.

About the LymPro Test
Developed by a major European research university, the initial clinical study for the LymPro Test demonstrated high positive correlation with clinical diagnosis and the potential to diagnose Alzheimer's disease before the appearance of clinical symptoms.
The LymPro Test recognizes and quantifies changes in cellular functions in blood samples that are indicative with Alzheimer's disease. These very specific protein expressions on the cell surface allow us to evaluate and differentiate between Alzheimer's disease, other dementias and healthy individuals.

About GW Medical Technologies LLC
GW Medical Technologies LLC is a translational in-vitro diagnostic company focused on the diagnosis of Alzheimer's disease. The company is poised to bring the LymPro Test to market as fast as possible with both U.S. and global approvals. Founded by Gartner and Everett G. Warren, chairman, GW Medical Technologies is located at 1440 E. Missouri Ave., Suite 225, Phoenix, AZ 85014. For more information about the company and the LymPro Test, visit www.GWmedtech.com or call 602-265-7862.

CONTACT:
GW Medical Technologies LLC, Phoenix Amy Armstrong, 602-265-7862 armstronga@GWmedtech.com

Health Sentinel, May 12, 2005 www.healthsentinel.com

93.Seniors Often Malnourished ? The Hidden Epidemic

Roman Bystrianyk, "Seniors Often Malnourished ? The Hidden Epidemic",

Many of us picture senior citizens enjoying an idyllic retirement. We visualize older adults spending time playing with grandchildren, pursuing hobbies, or even trying new careers. We like to believe in a vibrant and healthy time of life where people can enjoy their leisure years after a lifetime of work.
Unfortunately, that simple and serene picture is not a reality for many. The March issue of the American Journal of Nursing details what is essentially a hidden epidemic in our senior citizens today ? malnourishment. According to the study, malnourishment is, in fact, a greater threat to this population than obesity.
According to the study, “The Nutrition Screening Initiative [NSI], a multidisciplinary coalition headed by the America Dietetic Association and the American Academy of Family Physicians, estimates that 40% to 60% of hospitalized older adults are malnourished or at risk of malnutrition; it also estimates that 40% to 85% of nursing home residents suffer from malnutrition and that 20% to 60% of home care patients are so afflicted.”
There are many factors that contribute to malnutrition in seniors. Seniors can have little or no appetite, problems with eating or swallowing, inadequate servings, fewer than two meals a day, or insufficient hot meals. Another risk factor for malnutrition is poor dental health, which includes cavities, gum disease, and missing teeth.
Seniors can also suffer from xerostomia. Xerostomia is an abnormal dryness of the mouth resulting from decreased secretion of saliva. Antidepressants, antihypertensives, and bronchiodilators can contribute to xerostomia.
Malnourished older adults are also prone to frailty. Once a person is frail it can be the beginning of failing health. Frailty, was once termed failure to thrive in older adults, is now considered a distinct syndrome, a precursor to or a cause of disability. “Malnutrition has been identified as one of the four causes of frailty. Others include atherosclerosis, cognitive impairment, and sarcopenia (age related loss of muscle mass). Frail older adults are more likely to die, be hospitalized, or become disabled.”
Hospitalization itself can be a factor in undernutrition. In one study of elderly patients who had elective coronary artery bypass surgery several factors were measured to determine their nutritional health. The majority of patients before surgery had normal levels of albumin (low levels can be used as a marker for malnutrition), transferrin (a plasma protein that transports iron through the blood to the liver, spleen and bone marrow), and Body Mass Index (BMI). Five days after surgery, 85% of patients had a drop in albumin levels and 99% had a drop in transferrin. Four to six weeks after surgery both these levels were back to normal, however, BMI had decreased in 95% of the patients, and “the more weight patients lost, the more likely they were to be rehospitalized and report lower levels of physical health. These data suggest that hospitalization of elderly patients can cause profound changes in nutritional status that can remain into the unmonitored post-discharge period.”
Caregivers are sometimes inclined to employ the use of tube feeding as a way to offset the eating difficulties associated with advanced dementia in the elderly. However, a review of the evidence shows that there is no data, “to support tube feeding of demented patients with eating difficulties.” According to the journal article, “hand feeding is still considered the best intervention, and tube feeding should only be started if the patient ‘continues to decline in some clinically meaningful way’; tube feeding in this population ‘seldom achieves the intended medical aims and … rather than prevent suffering … can cause it.’ ”
According to a 2000 study supported by the Commonwealth Fund, “at least a third of the 1.6 million nursing home residents in the United States may suffer from malnutrition or dehydration, conditions that can aggravate or cause more severe medical problems such as tooth decay, broken bones, anemia, and low blood pressure?or in some cases even death.”
“Malnutrition, dehydration, and weight loss in nursing homes constitute one of the largest silent epidemics in this country,” said Karen Davis, president of The Commonwealth Fund. “We can address this problem by promoting changes in public policy, seeking creative solutions from providers and professionals, undertaking further research on key issues, and enforcing existing standards.”
High-calorie, nutrient-rich supplements are a good way to aid people who are not capable or unwilling to eat. The NSI states that improvement in body weight and survival has been shown in patients receiving oral supplements. One study of illness related to malnutrition in older adults concluded that, “oral nutritional supplements have a greater role than dietary advice in the improvement of body weight and energy intake.”
SOURCE: American Journal of Nursing, March 2005

12 May, 2005 BBC News

94.US scientists have invented a pill that can boost memory.

The drug CX717 belongs to a family of compounds called ampakines and works by boosting the brain chemical glutamate that makes learning and recall easy.
UK trials on 16 sleep-deprived volunteers showed it improved wakefulness and mental ability.
Its creator, Dr Gary Lynch from the University of California, told New Scientist it could be used to treat jet lag and diseases like Alzheimer's.
As you get tired, communication between brain cells begins to fail. When you take the pill, the communication is better
Manufacturer Cortex is considering CX717 as a possible treatment for narcolepsy - excessive daytime sleepiness; and attention deficit hyperactivity disorder (ADHD) - a condition which impairs a child's ability to concentrate.
It could also be taken by healthy people as a pick-me-up. But it will have to undergo further clinical trials before going on sale.
Dr Lynch explained how the drug works. "What it's doing is causing the neurons to communicate with each other a little better.
"As you get tired, communication between brain cells begins to fail. When you take the pill, the communication is better."
He said the drug appeared to have no side effects and because it was not a physical stimulant, like amphetamines, users would still be able to sleep.
Memory boost
In the UK trial, led by Julia Boyle and colleagues from the University of Surrey, healthy male volunteers aged 18 to 45 agreed to test the drug.
The volunteers started with a full night's sleep and the following morning and evening were asked to complete a battery of tests assessing memory, attention, alertness, reaction time and problem solving.
At 11pm they took either the real or dummy pills and stayed up through the night, being retested at midnight, 1am, 3am, 5am and 9am.
The volunteers who took the ampakine performed much better than those who took the fake drug.
Barbara Sahakian, Professor of Clinical Neuropsychiatry at Cambridge University in the UK, said: "There has been a lot of promise with the ampakines and people are very excited about them."
She said it could be useful for medical conditions that impaired memory and concentration, but warned against recreational use as has occurred with other stimulant drugs such as the ADHD medication Ritalin.
"I think it's something we have to be concerned about because some of those people taking these drugs, their brains are still developing and we do not know the long-term consequences."

14 May 2005 www.medicalnewstoday.com

95.Alzheimer's Patients' Ability to Make Decisions about Treatment, Study

People with very mild Alzheimer's disease are still competent to make decisions about their treatment, while those with moderate Alzheimer's may no longer be able to competently make those decisions, according to a study published in the May 10 issue of Neurology, the scientific journal of the American Academy of Neurology. The study also found that people who were aware of their Alzheimer's diagnosis, symptoms, and prognosis were more likely to be able to make competent decisions, regardless of the severity of their disease.
“These results are yet another reason why people should consult a doctor if they notice any warning signs of Alzheimer's in themselves or a loved one,” said study author Jason Karlawish, MD, of the University of Pennsylvania in Philadelphia. “An early diagnosis can help assure that patients can participate in decisions about their care.”
For the study, researchers interviewed 48 people with very mild to moderate Alzheimer's disease and 102 caregivers of people with mild to severe Alzheimer's. The patients' decision-making abilities were measured by giving them information about the benefits and risks of a hypothetical treatment for Alzheimer's and asking them to make a choice whether they would take the treatment. Then experts assessed whether they were competent to make the decision.
Of the 48 patients, 19 were found to be competent in making the decision.
The study found that scores on the Mini-Mental State Examination (MMSE), a widely used rating scale for cognitive abilities, can help predict patients' decision-making abilities. Those with scores of 11 to 19 on the scale, which indicates moderate dementia, were not likely to be competent decision-makers. Those with scores of 24 and higher, which indicates very mild dementia, were likely to be competent decision-makers.
Those with scores of 20 to 23, with mild to early moderate Alzheimer's, are in a gray zone, Karlawish said. “If there are questions about the competence of a person in this range, it would make sense to do a detailed assessment of that person's decision-making abilities,” he said. “Of course, the MMSE score is just one piece of information. People below this range are less likely to retain adequate decision-making abilities, but some may.”
Another finding of the study was that people who were aware of their diagnosis, symptoms, and prognosis were more likely to be able to make competent decisions. This insight into their condition was not related to the severity of the disease.
“This finding shows us that the mere presence of a dementia diagnosis does not preclude the patient from participating in decisions about his or her own care,” said neurologist Michael McQuillen, MD, MA, of the University of Rochester in Rochester, N.Y., who wrote an editorial accompanying the study.
Karlawish said, “The study also suggests that the loss of awareness of a patient's condition may be a sign that the patient is no longer able to competently make decisions about their treatment.”
The study also found that 40 percent of the patients could understand how the risks of the hypothetical treatment would apply to them, while only 15 percent could appreciate how the treatment's benefits would apply to them.
Karlawish said the results may be helpful because, while current Alzheimer's treatments have few substantial risks, potential treatments that are under development may have substantial risks. “Doctors and family members could benefit from having a method to know if the person is capable of deciding whether to undergo a risky treatment,” he said.
The study was supported by grants from the National Institute on Aging, a Paul Beeson Physician Faculty Scholars in Aging Research award from the John A. Hartford Foundation, and a Greenwall Faculty Scholar in Bioethics award from the Greenwall Foundation.
The American Academy of Neurology, an association of more than 18,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer's disease, epilepsy, Parkinson's disease, autism and multiple sclerosis.
For more information about the American Academy of Neurology, visit its web site at http://www.aan.com.

13th May 2005　www.dailymail.co.uk

96.Drugs warning over dementia

Patients with dementia are still being prescribed dangerous drug treatments despite a warning from medicines experts, campaigners said.
Last year the Committee on the Safety of Medicines (CSM) ruled that neuroleptic drug treatments - used as a sedative - should not be given to dementia sufferers because of a threefold increase in the risk of stroke.

But the Alzheimer's Society said 81% of people prescribed the drugs before the warning were still receiving them a year later.

Last month the Food and Drug Administration (FDA) in the United States warned that neuroleptic treatments increased the risk of death in people with dementia.
The FDA pointed out that 17 controlled studies of people with dementia showed that those given the drugs were up to 1.7 times more likely to die than patients given a placebo.

In March last year the CSM said that the neuroleptic drugs risperidone and olanzapine should not be used to treat behavioural symptoms in people with dementia because they increased the risk of stroke by up to three times.

An estimated 30,000 patients over 65 were receiving risperidone and 9,000 were receiving olanzapine for dementia in 2003.

The CSM said that while these drugs were licensed to treat acute psychosis and schizophrenia, they were also prescribed "off label" to deal with behaviour problems in older people with dementia with some evidence of benefits.

The Alzheimer's Society carried out research at 12 nursing homes across the UK, involving 166 people with dementia.

They found that 42% of people with dementia living in care homes were still being prescribed neuroleptic drug treatments.

May 16, 2005　http://news.yahoo.com

97.Alzheimer's Disease Drug Market to Exceed $5 Billion by 2009

(PRWEB) - (PRWEB) May 16, 2005 -- Alzheimer"s is a degenerative disease that will affect 10 million people in the G7 countries by 2009. Currently more than 10% of Americans age 65 or older suffer from Alzheimer"s disease (AD), of which only a quarter receive AD drug medications. The advent of new drugs has revolutionized AD care. According to Millennium Research Group"s new Global Markets for Alzheimer"s Disease Medications 2005, the market for AD drug therapy in the US, Europe, and Japan will generate over $3 billion in 2005, with the US accounting for over 60% of market revenues. As aging baby boomers throughout the developed world enter the high-risk years for AD, the market for AD drugs will grow rapidly, reaching $5.5 billion by 2009.
In its new report, Millennium Research Group (MRG) measures the influence of a range of trends and new developments on the use of AD drugs in the US, Europe, and Japan. By separating mild ? moderate from moderate ? severe indications, and existing treatments from future practices, the report forecasts 15% annual growth over the next five years. In addition to predicting the continued dominance of Eisai (ESALY.PK)/Pfizer"s (PFE) Aricept, and the strong growth of memantine-based drugs such as Forest Laboratories" (FRX) Namenda, other companies covered in the report include: Andr?maco Laboratories, Bracco, First Horizon Pharmaceutical Corp (FHRX), Janssen Pharmaceutica (JNJ), Laboratorios Esteve, Lundbeck (HLUKF.PK), Merz Pharma, Novartis (NVS), OTL Pharma, Shire Pharmaceuticals (SHPGY), and Sigma-Tau Research, Inc.

MRG is a leading player in health care competitive intelligence. With over 50 analysts and researchers, we publish over 80 reports on the global health care market annually.

Contact Information:
Nilesh Patel
Millennium Research Group Inc.,
+1 (416) 364-7776 ext. 121
email protected from spam bots
www.mrg.net

The Local Sweden’s news in English
16th May 2005

98.Sweden to test new Alzheimer's vaccine

A new vaccine against Alzheimer's disease will be tested on 60 Swedish patients at initial or moderate stages of degenerative neurological dementia, Swedish media reported on Sunday.
The CAD 106 vaccine is to "activate the immune system for it to produce antibodies" against the protein which forms the platelets believed to block nervous cell signals in the brain, daily Dagens Nyheter reported.
The platelets, created by amyloid beta protein, are thought to be the cause of the irreversible disease. One fifth of the 60 patients will be given a placebo treatment during the one-year trial carried out at a hospital in Stockholm and one in the southern Swedish city of Malm?.
The vaccine was tested on mice and the "platelets had nearly disappeared after 12 weeks of treatment," said the newspaper.
The daily reported that a first vaccine trial carried out in the United States and in France in 2000 had to be stopped because of the side effects it caused in the patients. Some patients suffered from inflammations, including inflammations of the brain.
But Bengt Winblad, the professor in charge of the trial, said the CAD 106 vaccine was more specific and should succeed in activating the antibodies without stimulating immune systems cells which caused the inflammations.
Alzheimer's affects an estimated 10 million people worldwide, usually after the age of 65. Some 120,000 Swedes suffer from the degenerative brain disease which causes dementia. (AFP)

-------------------------------------

21st April 2005
Swedish vaccine gives hope of Alzheimer's cure
A group of Swedish researchers has developed a new vaccine to combat the development of Alzheimer's disease. Within the month scientists will start testing the vaccine on animals, and provided that gives good results, human trials will start within three years.
"We want to try and use the vaccine early on in the development of the illness," says Lars Lannfelt, Professor of Geriatrics at the Academic Hospital in Uppsala, "in the hope that we can stop the illness from developing fully."
Lannfelt and his research team have been making key discoveries in the Alzheimer's field. Five years ago they identified two human mutations that affect the level of amyloid peptide in the brain. Individuals that have inherited these mutations develop early onset Alzheimer's disease, providing strong evidence that amyloid peptide contributes to the development of the disease.
Speaking to Dagens Nyheter Professor Lannfelt said: "we believe that it is actually these poisonous pre-stages that ultimately result in the illness. The brain is actually trying to protect itself by making these deposits".
The antibodies that make up the vaccine were discovered thanks to a breakthrough five years ago, when Lannfelt and his research team at the Karolinska Institute discovered a specific genetic mutation in the gene that controls the production of beta amyloid, a protein that builds up in the brains of persons with Alzheimer's disease, collecting in clumps called senile plaques.
Once the deposits have begun to develop in the brain, chronic inflammation kills off the nerve cells and makes the brain shrink. This mutation is known as the ‘Arctic mutation’ because it was found in an abnormally high number of Alzheimer's patients in the far north of Sweden.
The antibodies will now be tested on mice. "We are the first research group in the world to have developed a vaccine with this approach", says Lannfelt. It will take about a year following results from animal testing to develop a vaccine that can be tested on humans.

Lysanne Sizoo
Lysanne Sizoo is a certified counsellor, specialising in bereavement, fertility and cultural assimilation issues. She also runs a support and discussion group for English speaking women. You can contact her on sizoo@swipnet.se, or 08 717 3769. More information on www.sizoo.nu.

May 18, 2005 　www.medadnews.com

99.Immunodrug Candidate CAD106, a Potential Treatment for Alzheimer’s Disease, Obtains Clearance from Swedish Health Authority to Enter Phase I Clinical Trial
Cytos Biotechnology receives a development milestone payment from Novartis

SCHLIEREN (ZURICH), Switzerland, May 18, 2005 ? Cytos Biotechnology AG (SWX:CYTN) today announced that its collaboration partner Novartis Pharma AG has obtained approval from the Swedish health authority to initiate a phase I clinical trial with the Immunodrug? candidate CAD106, an immunotherapeutic product for the treatment of Alzheimer’s disease. The achievement of this milestone will trigger an undisclosed payment to Cytos Biotechnology.

CAD106 treatment aims at the generation of antibodies against the ?-amyloid-protein that inhibit the formation of “plaques” involved in the Alzheimer’s disease process. CAD106 is the product of the collaborative program between Novartis and Cytos Biotechnology first announced in October 2001. The double-blind and placebo-controlled phase I study planned and conducted by Novartis will include 60 patients with mild to moderate Alzheimer’s disease and will investigate safety, tolerability and ?-amyloid specific antibody response following treatment with CAD106. Novartis expects patient recruitment to start in the course of 2005 and first results of the study to be available in 2007.

Wolfgang Renner, CEO at Cytos Biotechnology, comments: “This collaboration allying the comprehensive preclinical and clinical knowledge from Novartis with our innovative ImmunodrugTM platform and cutting-edge science has been very productive. Within less than four years, CAD106 advanced from early research into clinical development and I am delighted to see the progress of this collaboration with Novartis in such an important disease indication.”

About the Immunodrug? candidate CAD106

CAD106 is an immunotherapeutic product in development for the treatment of Alzheimer’s disease. CAD106 is designed to induce antibodies against the ?-amyloid-protein that inhibit the formation of plaques in the brain of Alzheimer’s disease patients. CAD106 consists of two components, the Immunodrug? carrier Qb coupled with a fragment of the ?-amyloid-protein. In animal studies it has been shown that treatment with CAD106 can block the formation of ?-amyloid plaques in the brain. Since the formation of such plaques is considered a hallmark of the disease, CAD106 may offer the potential to advance the treatment of Alzheimer’s disease.

About Alzheimer’s disease

Alzheimer’s disease is a progressive, degenerative disease that alters the brain, causing impaired memory, thinking and behaviour. The onset of Alzheimer’s disease is usually after 65 years of age, though earlier onset is not uncommon. Alzheimer’s disease affects approximately 5-6% of people aged 60 and older and as age advances, the incidence increases rapidly (WHO, 2001). This has an obvious implication for the total number of individuals living with this disorder in the future as life expectancy increases in the population.

The exact cause of Alzheimer’s disease remains unknown, although a number of factors have been suggested. In damaged areas of the brain “plaques” and “tangles” made from ??amyloid-peptide (A?) and tau are observed under the microscope, which are characteristic features of Alzheimer’s disease and considered to be involved in the disease process. There is as yet no cure for this disease. The currently approved treatments only provide symptomatic relief for Alzheimer’s patients. Preliminary evidence provided by an independent team applying another immunization strategy suggests that active immunization against ??amyloid-protein has the potential to slow cognitive decline in patients with Alzheimer’s disease (Neuron, 2003, 38:547). Although current research is still at an early clinical stage, immunotherapy may represent a promising new strategy for treatment and prevention of Alzheimer’s disease.

About Cytos Biotechnology AG

Cytos Biotechnology AG is a public Swiss biotechnology company that specializes in the discovery, development and commercialization of a new class of biopharmaceutical products ? the ImmunodrugsTM. ImmunodrugsTM are intended for use in the treatment and prevention of common chronic diseases, which afflict millions of people worldwide. ImmunodrugsTM are designed to instruct the patient’s immune system to produce desired therapeutic antibody or cytotoxic T-cell responses that modulate chronic disease processes. Taking advantage of the high flexibility of its ImmunodrugTM platform, Cytos Biotechnology has built a pipeline of 27 different ImmunodrugTM candidates in various disease areas, of which seven are currently in clinical development. The Immunodrug? candidates are developed both in-house (24) and together with Novartis (1) and Pfizer Animal Health (2). Founded in 1995 as a spin-off from the Swiss Federal Institute of Technology (ETH) in Zurich, the company is located in Schlieren (Zurich). Currently, the company has 110 employees. Cytos Biotechnology AG has been listed on the SWX Swiss Exchange (SWX:CYTN) since October 2002.

For further information please contact:

Cytos Biotechnology AG
Dr. Claudine Blaser
Director Corporate Communications
Phone: +41 44 733 47 20
Fax: +41 44 733 47 18
e-Mail: claudine.blaser@cytos.com
Website: www.cytos.com

May 18, 2005　www.medadnews.com/

100.New Promising Treatment of Alzheimer's Disease
Successful Completion of Phase I Study

COPENHAGEN, Denmark, May 18, 2005 ? Today ENKAM Pharmaceuticals A/S announces the completion of the first phase I clinical study for the synthetic peptide FGLL, which proved to be well tolerated and safe. In the study 24 healthy males received FGLL by intranasal administration at one of three dose ranges.

Throughout a broad range of models, including one Alzheimer Model, FGLL showed both neuroprotection and improvement of the memory and learning capability, which gives promise for FGLL to effectively treat Alzheimer’s disease. Furthermore FGLL also demonstrated enhancement of memory and learning capability in normal animals.

“The effect of the molecule is unique by making the nerve cells much more vital and improving their communication. We therefore expect that FGLL can positively affect the ability of patients to learn and remember,” says co-founder and professor Elisabeth Bock, MD.

Blockbuster potential

Following the successful completion of this study with FGLL ENKAM now plans to progress the development of FGLL into phase II. To accelerate the development of FGLL through phase II and to the market ENKAM is actively pursuing a partnership.

“If we can achieve the same results in humans that we registered in the pharmacological studies this is a treatment with blockbuster potential,” states Morten Albrechtsen, MD and CEO at ENKAM.

FGLL ? a different and unique approach

FGLL emerged from ENKAM’s research of the protein NCAM (the Neural Cell Adhesion Molecule). FGLL is a synthetic peptide able to prevent and contra-act beta-amyloid accumulation, the major hallmark of Alzheimer’s disease. Furthermore FGLL seems to prevent brain cells from dying and to restore the functionality of the already affected brain cells.

“FGLL belongs to a novel class of drugs, namely the NCAM mimetics that selectively target the FGF receptor in the brain. In the preclinical research FGLL reduced amyloid load, protected neurons from dying and normalised short and long term memory,” explains the Head of Clinical Development Ravi Anand, MD, who has been working for more than two decades in clinical development where he has developed several marketed CNS treatments.

For further information, please contact:

Morten Albrechtsen, CEO, tel.: +45 24 25 62 66

About ENKAM Pharmaceuticals

ENKAM Pharmaceuticals A/S is a biotechnological company, established in 2000 as a spin-off from the University of Copenhagen. ENKAM has a unique scientific approach to developing drugs for CNS diseases. The Danish company identifies small peptides (pieces of protein), which occur naturally in the brain, with the objective to identify peptides that offer a potential in the treatment of brain diseases.

Notes for editors:

About Alzheimer’s Disease

Alzheimer’s is a progressive disease in the Central Nervous System (CNS) affecting middle-aged and elderly people. There is no cure for the disease which has a significant negative impact on the quality of life. It manifests itself through cognitive symptoms (loss of memory and failure to learn new things) and emotional symptoms (anxiety and depression). Current treatments only produce partial relief. The therapeutic area for CNS diseases is one of the fastest growing. In 2003 the market for drugs to treat Alzheimer’s disease grew by 38% calculated in USD.

Definitions:

FGLL

FGLL is a chemically synthesised peptide, with strong structural similarity to naturally occurring peptides and with positive biological effects on the neuronal cells and the brain. The compound mediates the positive effects known from growth factors without their side effects. FGLL is a NCAM mimetic (see below) and works by revitalising nerve cells in particular.

NCAM ? The Neural Cell Adhesion Molecule

The molecule lies in the surface of the cells in the Central Nervous System (CNS) and plays an important role in the survival of the neurons, the stimulation of the nerve system’s stem cells and the neurons’ activity. NCAM binds to itself and to a series of counter-receptors, including the FGF receptor.

NCAM mimetics

By means of combinatorial chemistry and based on the unravelling of the structure of NCAM, it has been possible to develop a number of peptides that mimic NCAM way of binding. These peptides interfere with cell adhesion and promote differentiation and cell survival.

Fibroblast Growth Factor (FGF) receptor

FGF is a group of g rowth factors that act on the fibroblast (basic building blocks of fibrous tissue) within the body. Most cells within the brain, nervous system and other organs possess receptors for FGF and are therefore susceptible to its biological effect. There are at least 19 distinct members of the FGF family, which interact with at least 4 distinct types of cell-surface receptors. It is evident that the amount of FGF is essential for optimum body function, and disruption of FGF can lead to disease states .