Alzheimer's Takes Hold Long before Decline

Apparently healthy people with no sign of mental decline may already have significant Alzheimer's disease, new studies show.

This "preclinical Alzheimer's disease" puts a person at high risk of an eventual diagnosis of Alzheimer's disease, find studies led by John C. Morris, MD, director of the Alzheimer's Disease Research Center at Washington University, St. Louis.

Morris and colleagues studied 135 people at ages ranging from 65 to 88. They were "sharp as a tack" on sophisticated tests of mental function, Morris says.

But brain scans showed that more than 22% already had the telltale plaque deposits in their brains that characterize Alzheimer's disease.

A second study of 159 people at an average age of 71 showed that those with this "preclinical Alzheimer's disease" were nearly five times more likely to develop very mild Alzheimer's-type dementia.

"Now we have a revolutionary change in Alzheimer's disease," Morris tells WebMD. "This is the first evidence that people who were perfectly healthy had amyloid plaques, and that these individuals are at very high risk of symptoms of Alzheimer's disease over a three- to four-year period."

These are major findings, agrees Gary Kennedy, MD, director of geriatric psychiatry at Montefiore Medical Center in New York. Kennedy was not involved in the Morris study.

"The reason this is important is we would like to identify people with this illness before they get disabled," Kennedy tells WebMD. "If we had agents that really slowed down the progression of Alzheimer's disease, we could forestall disability to end of a person's lifetime, and the burden of Alzheimer's disease on society would level off."

That day remains far off. The bad news from the Morris studies is that by the time people show clinical signs of Alzheimer's disease -- currently the only way this fatal illness is diagnosed -- it may be too late. Such symptoms now appear to be the result of irreversible brain damage.

"Even if we knew you had preclinical Alzheimer's disease in your brain and ergo high risk of symptoms in a few years, we can't do anything about it now," Morris says. "So I really think we have to follow a dual course. We have to clarify, refine, and define our clinical detection of Alzheimer's disease -- but at the same time we have to develop treatments for prevention. Because we would like to couple knowing your risk with reducing your risk."

While the brain scans were able to detect the buildup of amyloid plaque in the brain, a different test -- one that checks for Alzheimer's biomarkers in cerebrospinal fluid -- may detect Alzheimer's risk even earlier.

Morris and colleagues studied one patient who eventually died with Alzheimer's disease. He was positive for the biomarker but his brain scan did not detect signs of Alzheimer's.

Kennedy says that's a hopeful finding. To him, it suggests that Alzheimer's disease is not one single entity, but may be a family of diseases that may respond to different treatments.

Morris notes that it's still too soon to be able to tell from brain scans or biomarkers exactly how long it will take for a healthy person with pre-Alzheimer's to develop dementia. But he expects this will eventually be possible.

"As experience accumulates, we will be able to determine in these people who carry lesions when they will get symptoms of Alzheimer's disease," he says. "It will not be straightforward. It will vary with a host of individual factors. But we can expect a day when we can tell people where they are in the course of preclinical Alzheimer's disease, and their risk of dementia in one or 10 or 20 years."

The Morris studies were funded with grants from the National Institute on Aging, an anonymous foundation, and by the Knight Alzheimer's Research Initiative of Washington University. The studies appear in the December issue of Archives of Neurology.
By Daniel DeNoon
Reviewed by Louise Chang
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