Source: LA Times
Date: 26 July 2004

Drug reported to slow
the onset of Alzheimer's

In the study, high-risk patients who took donepezil
experienced a six-month delay in progression to the disease.

By Rosie Mestel,
Times Staff Writer

In an impressive step forward, scientists have reported for the first time that they had delayed the onset of Alzheimer's in a group of high-risk patients, using an Alzheimer's drug known as donepezil.

The finding is preliminary, the delay experienced by the patients just six months. But the study, reported at a scientific meeting, offered hope that the disease might one day be warded off long enough so that people at high risk would be more likely to die of other causes before ever developing dementia.

"It's extraordinarily encouraging," said Marcelle Morrison-Bogorad, an associate director at the National Institute on Aging. "This is really the beginning, I hope, of a wave of positive results over the next few years."

Thousands of scientists gathered in Philadelphia last week for the International Conference on Alzheimer's Disease and Related Disorders, listening to wide-ranging reports on brain chemistry, demented rats, Alzheimer's genes and high-tech imaging.

There was no report of any miracle cure for the brain-destroying disorder, which afflicts an estimated 4.5 million Americans. But there were plenty of developments that should help scientists better understand and diagnose the disease and devise new therapies.

  • Much attention fell on the donepezil trial, conducted by a team of scientists at 69 medical centers in the U.S. and Canada. The trial's 769 patients had been diagnosed with a condition known as mild cognitive impairment, in which people have unusual memory problems for their age and have a 10% to 15% annual risk of advancing to an Alzheimer's diagnosis.

    In the trial (funded by the government and two drug companies that manufacture donepezil), each participant received one of three treatments donepezil, a placebo or Vitamin E. At the end of three years, there was no detectable difference among the three groups. However, patients taking donepezil experienced a six-month delay in progression to Alzheimer's during the first 18 months of the study.

    Dr. Ronald Petersen, lead author of the study and a Mayo Clinic neurologist, said more statistical analysis is needed to shore up the findings. Similar trials on patients with mild cognitive impairment are in progress, testing a variety of drugs.

  • Several groups of scientists presented medical imaging techniques that can be used to view the abnormal tangles and plaques that build up in the brains of Alzheimer's patients.

    One team, led by Dr. William Klunk at the University of Pittsburgh, has created a chemical that binds directly to the plaques inside Alzheimer's patients' brains. Another, led by Dr. W. Gary Small, director of the UCLA Center on Aging, has a chemical that binds to plaques and to tangles.

    When the chemicals are injected into a patient's vein, they travel to the brain, then bind to these abnormal structures. They can be clearly viewed using a brain-imaging technique known as positron emission tomography, or PET. These methods show that many people with mild cognitive dementia already have plaques and tangles in their brains.

    Once the technology is fine-tuned, it could be used in clinical trials to test potential new drugs and significantly lower the cost of such trials, Small said. It might also help with diagnosis: Small's group has found that people with a rare kind of Alzheimer's disease (called frontotemporal dementia) have a very different brain image from those with the more common kind.

    Imaging might even help predict which patients with mild cognitive impairment are destined to develop full-blown Alzheimer's disease. Klunk's group has found that only some of the patients with mild cognitive dementia show increased amounts of toxic amyloid plaques in their brains.

  • Several studies suggested that different racial groups may have different risks for Alzheimer's. One study, conducted at Alzheimer's disease centers around the United States, found that the first symptoms of Alzheimer's appear to show up 6.8 years earlier in Latinos compared with non-Latinos.

    Another, from the University of South Carolina, reported that African Americans, ages 55 to 64, were more than three times as likely to have a diagnosis of Alzheimer's as Caucasians of similar ages. Experts said there are many explanations for these findings from genetics to lifestyle and cultural differences that cause some groups to fare poorer on the diagnostic tests.

  • Evidence is mounting that lifestyle plays a significant role in reducing a person's risk of dementia, especially staying socially and intellectually engaged and adopting habits that are good for the heart.

    In one study, a group of Swedish and Finnish researchers tracked nearly 1,500 elderly men and women for 21 years and found that those who had been obese when they were middle-aged were twice as likely to develop dementia when they were older. The risk climbed even higher to six times that of those without these risk factors when high cholesterol and high blood pressure were added.

    In another study, Harvard researchers who've been tracking the diets of thousands of nurses for many years reported that the women who had eaten the most green, leafy vegetables and vegetables from the broccoli and cabbage family experienced less cognitive decline as they aged.

    Because these are hard-to control studies of populations, it's not proven that eating well and staying trim directly reduce a person's dementia risk, Morrison-Bogorad said.

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