Alzheimer's experts at UCSD will lead a $60 million effort at 50 U.S. and Canadian centers to identify the earliest physical changes in patients' brains in a quest to find drugs to stop the dementia process almost before it begins.

Mild cognitive impairment leading to Alzheimer's is largely diagnosed based on how patients score on a series of simple functional and memory tests.

Results can vary greatly depending on mood, diet and how well the patient slept the night before, said Dr. Leon Thal, chairman of the University of California San Diego department of neurosciences and director of the National Alzheimer's Disease Cooperative Study. That also makes it difficult to determine which drugs work and which don't, or may even cause harm.

"Right now, our ability to diagnose mild cognitive impairment is not extremely good," said Thal, who will coordinate research on the 800 participants in the five-year study. "The earlier the condition is, the harder it is to diagnose."

The Alzheimer's Disease Neuroimaging Initiative is designed to improve that diagnostic capability by measuring brain and central nervous system changes through magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, as well as numerous inflammation markers in blood and spinal fluid.

Specifically, researchers will use imaging techniques to quantify the volume of the hippocampus, the part of the brain that governs memory and is known to dramatically shrink as Alzheimer's disease progresses.

In addition to changes in the hippocampus, the study will explore the use of biochemical markers to identify the earliest stages of disease and track its course.

Tests of blood, spinal fluid or urine revealing levels of glucose, certain markers for inflammation and the amount of beta-amyloid and tau – substances believed to contribute to the formation of tangles and plaques in Alzheimer's patients' brains – all may be used in the diagnostic process.

The project is a collaboration among several federal agencies within the National Institutes of Health and the Food and Drug Administration and nine pharmaceutical companies, which hope to use these markers of Alzheimer's progression to learn whether any of their candidate drugs will do any good.

Of the $60 million, one-third comes from the pharmaceutical companies and the Institute for the Study of Aging.

Starting in April 2005, 200 normal older individuals, 400 participants with mild cognitive impairment and 200 patients with early Alzheimer's disease will be recruited for two-or three-year study intervals. Many will receive compensation.

Participants will be between the ages of 55 and 90.

About 30 will come from San Diego County, Thal said.

Health experts estimate that about 4.5 million people nationally suffer from Alzheimer's disease. They experience deteriorating ability to remember not only how to perform tasks in everyday life, but the faces of their closest family members and friends.

Dr. Richard Hodes, director of the National Institute on Aging, called the effort "a landmark study . . . helping us to find biological changes early so that we can identify the people at highest risk of the disease and test effectiveness of new therapies more quickly and efficiently."