During the past few years, researchers have searched fervently for ways to identify people at risk for Alzheimer's disease before these individuals develop any symptoms. Several groups have detected structural changes in the brain that appear to precede the disease's clinical onset, often marked by memory impairment. And now Mony J. de Leon of the New York University School of Medicine and colleagues report in today's issue of the Proceedings of the National Academy of Sciences that they have discovered metabolic changes in the brains of healthy men and women that can also predict impending memory problems.

The scientists studied 48 subjects between 60 and 80 years old, all of whom initially scored within the normal range on tests used to detect early memory loss. PET scans revealed that 12 of these subjects showed reduced glucose metabolism in a brain region called the entorhinal cortex. When de Leon and crew reevaluated these same 12 people three years later, they found that 11 had experienced mild cognitive impairment (MCI), a condition that often leads to Alzheimer's, and one had developed Alzheimer's disease. Also among this group, carriers of the apolipoprotein E4 gene¿a marker linked to Alzheimer's¿showed dramatic drops in brain metabolic activity. The remaining subjects with normal PET scans suffered no mental decline during the course of the study.

"Our work extends the use of PET scanning to identifying in normal aging subjects the earliest metabolic abnormalities that may lead to the memory losses referred to as MCI," de Leon says. "The results will allow us to distinguish individuals at increased risk of memory impairment, but it is still too early to apply the brain scans outside of a research setting. We need to confirm our results with a larger group of subjects and to identify the biological and physiological factors leading to the metabolism losses. If we can identify these factors, then we may be able to find a way to delay the onset of Alzheimer's or prevent it altogether."