Brain changes may foretell Alzheimer's.

Brain changes may

foretell Alzheimer's

Subtle alterations in brain function may foreshadow the onset of Alzheimer's disease in genetically at-risk middle-aged people, according to a new report.

"The findings suggest there are changes going on years before the disease can be confirmed clinically," says lead researcher Gary W. Small of the University of California, Los Angeles, School of Medicine.

Small and his colleagues recruited 31 men and women age 50 or older from families with a history of Alzheimer's disease. These high-risk volunteers all had mild memory complaints, such as misplacing familiar objects. However, they all performed normally on tests of cognitive function. The researchers wondered if they could identify those who would go on to develop Alzheimer's disease, which causes severe memory loss.

All of the subjects underwent a scanning procedure called positron emission tomography (PET). This test allows researchers to gauge the brain's use of glucose, a sugar that provides nourishment for nerve cells. Small's team knew that PET scans of people with Alzheimer's disease reveal a decreased ability to utilize glucose, a deficit that starts initially in the parietal cortex (see photo). This brain region is associated with memory, language, and other functions impaired by the disease process. Yet those scans had never been shown to flag otherwise healthy people who later succumbed to Alzheimer's disease. So the researchers decided to add a genetic assessment to their study design.

They knew that a team at Duke University Medical Center in Durham, N.C., had previously linked a gene known as apolipoprotein E-IV to Alzheimer's disease (SN: 1/1/94, p.8). This prompted Small's group to collect blood samples from its recruits. Twelve of the 31 had inherited this risky gene. The group then combined the brain scan and genetic testing results. The 12 volunteers who carried apo E-IV displayed significantly reduced glucose utilization in the parietal region, compared to the 19 who did not inherit this gene. The researchers report their results in the March 22--29 Journal of the American Medical Association.

The reduction in glucose metabolism suggests that the neurons in the parietal region either aren't working well or have died, points out Zaven S. Khachaturian, an Alzheimer's researcher at the National Institute on Aging in Bethesda, Md. For people without dementia, such slight changes may be the first step in a decline leading many years later to full-blown disease, he says.

If researchers can identify such people, they may be able to test experimental drugs aimed at preventing the nerve cell death that underlies Alzheimer's disease.

The ultimate goal is "not only to identify these people early, but to have an intervention so that you can actually stop the [disease] process in its tracks," says Sheryl L. Williams of the Chicago-based Alzheimer's Association. Still, the researchers emphasize that other groups must verify their results. "These are preliminary findings," Small says.