Finding Alzheimer's before a mind fails

For a perfectly healthy woman, Dianne Kerley has had quite a few medical tests in recent years: MRI and PET scans of her brain, two spinal taps and hours of memory and thinking tests.

Kerley, 52, has spent much of her life in the shadow of an illness that gradually destroys memory, personality and the ability to think, speak, and live independently. Her mother, grandmother and a maternal great-aunt all developed Alzheimer's disease. Her mother, 78, is in a nursing home in the advanced stages of dementia, helpless and barely responsive.

"She's in her own private purgatory," Kerley said.

Kerley is part of an ambitious new scientific effort to find ways to detect Alzheimer's disease at the earliest possible moment. Although the disease may seem like a calamity that strikes suddenly in old age, scientists now think it begins long before the mind fails.

"Alzheimer's disease may be a chronic condition in which changes begin in midlife or even earlier," said Dr. John C. Morris, director of the Alzheimer's Disease Research Center at Washington University in St. Louis, where Kerley volunteers for studies.

Currently, the diagnosis is not made until symptoms develop, and by then it may already be too late to rescue the brain. Drugs temporarily ease symptoms for some, but cannot halt the underlying disease.

Many scientists believe the best hope of progress, maybe the only hope, lies in detecting the disease early and devising treatments to stop it before brain damage becomes extensive.

Better still, they would like to intervene even sooner, by identifying risk factors and treating people preventively - the same strategy that has markedly lowered death rates from heart disease, stroke and some cancers.

So far, Alzheimer's has been unyielding. But research now under way may start answering major questions about when the disease begins and how best to fight it.

A radioactive dye called PIB (for Pittsburgh Compound B) has made it possible to use PET scans to find deposits of amyloid, an Alzheimer's-related protein, in the brains of live human beings.

It may lead to earlier diagnosis, help doctors distinguish Alzheimer's from other forms of dementia and let them monitor the effects of treatment.

Studies with the dye have found significant deposits in 20 percent to 25 percent of seemingly normal people over 65, suggesting that they may be on the way to Alzheimer's, though only time will tell.

"PIB is about the future of where Alzheimer's disease needs to be," said Dr. William E. Klunk, a co-discoverer of the dye at the Alzheimer's research center at the University of Pittsburgh. "PIB is being used today to help determine whether drugs that are meant to prevent or remove amyloid from the brain are working, so we can find drugs that prevent the underlying pathology of the disease."

Though PIB is experimental now, studies began in November that are intended to lead to government approval for wider use.

For the most common form of Alzheimer's disease, which occurs after age 65, there is no proven means of early detection, no definitive genetic test.

But PIB tests might be ready before new treatments emerge, making it possible to predict who will develop Alzheimer's - without being able to help.

Researchers are also using MRI scans to look for early brain changes, and testing blood and spinal fluid for amyloid and other "biomarkers" to see if they can be used to predict Alzheimer's or find it early.

Studies of families in which multiple members have dementia are helping to sort out the genetic underpinnings of the disease.

Experiments also are under way to find out whether drugs and vaccines can remove amyloid from the brain or prevent its buildup, and whether doing so would help patients. The new drugs have the potential to stop or slow the progress of the disease.