PET scans of a normal brain and that of an Alzheimer's patient with the hallmark metabolic deficit in the parietal and temporal cortices.

 

The gene at issue has codes corresponding to a protein called apolipoprotein E (APOE). Everyone has two copies of the gene, one inherited from each parent. The APOE gene comes in three variants, known as APOE2, APOE3, and APOE4. Anyone who inherits one or two copies of the E4 variant has a greatly increased chance of developing Alzheimer's as they age. The exact reason for his is still a hotly debated issue, but researchers suspect APOE4 may somehow contribute to the accumulation of the protein amyloid in the numerous brain plaques that constitute one of the hallmarks of the disease. "No one knows the underlying mechanism of how APOE works in the brain," says Small. "At this point we're looking at it as a means of early detection." In one study, Small and his colleagues conducted positron emission tomography (PET) scans (see "Mapping the Brain,"Challenge, 1994) of the brains of people in their 50s who reported mild memory problems. The researchers then compared people who possessed the APOE4 gene with those who did not. PETscanning, invented by collaborator Michael Phelps of UCLA, is a powerful brain-imaging technique that shows a characteristic pattern in patients who have already developed Alzheimer's. In Small's study of people with mild memory complaints, those who had the gene for Alzheimer's showed decreased metabolism in the parietal region of the brain, an area which is associated with many higher cognitive functions and which suffers great damage as Alzheimer's disease progresses. But early detection of Alzheimer's is not as simple as merely measuring whether a person has the E4 variant. Many people with APOE4 never develop Alzheimer's disease, and many people with Alzheimer's do not possess the APOE4 gene.  Nevertheless, Small and his group were the first to show that the APOE4 gene is a relatively strong predictor of Alzheimer's, especially the most common late-onset form of the disease. In addition, Small and colleagues like Susan Bookheimer are developing a cognitive stress test similar in concept to the treadmill-based stress tests that are designed to assess heart function. In the treadmill test, the heart is stressed by moderately heavy exercise while an electrocardiogram measures the heart's electrical   activity.  In Small's cognitive test, the brain is stressed with a moderately difficult memory task. Subjects are given seven pairs of unrelated words. After a brief interval, they're prompted with the first word in the pair and asked to recall the second one. Simultaneously, the subjects' brain function metabolism is measured by functional magnetic resonance imaging (fMRI). Small's initial experiments with the cognitive stress test compared older volunteers who have the APOE4 gene to those who don't. During the memory test, the volunteers with APOE4 showed higher activity in several regions of the brain, especially in the medial temporal region, an area associated with memory processing. But why would the people most at risk for Alzheimer's show more brain activity than the control subjects? Says Small: "Our theory is that there are subtle deficits, and the brain is trying to compensate for these deficits." Put simply, a brain with incipient Alzheimer's disease must work harder than a normal brain to accomplish the same goal. The ultimate goal for Small, however, goes beyond even the best science. "Advances in medical technology have helped us live longer," he notes. "But are we living better? We want to improve the quality of life as we age."

 

Quality--and Equality--of Care

 

ntil cures for diseases like Alzheimer's are discovered, the number of people requiring long-term care in old age is bound to increase dramatically as the huge generation of baby boomers ages. The economic, social and medical questions associated with long-term care are enormously complex. But according to studies by Associate Professor of Public Health Steven P. Wallace, one of these complexities involves the fact that society apparently treats elderly members of racial and ethnic minorities differently than non-Hispanic whites. "The health status of the elderly differs by race and ethnicity—on almost any measure that you can think of," notes Wallace. "For example, African-American elderly have higher death rates, illness rates and disability rates than non-Hispanic whites." Wallace is associate director of the UCLA Center for Health Policy Research. Being named the first Borun Scholar at the Borun Center for Gerontological Research has provided him the resources to study managed care, long-term care and minority elderly. His research is also supported by the Wellness Foundation, Wilshire Foundation, AARPPublic Policy Institute, California Endowment and California HealthCare Foundation. He began investigating the causes of what others had documented as apparent disparities in the health—and treatment—of this group. In setting up his study, Wallace attempted to take into account the complexity of the issue by neutralizing the effects of gender, education, income, the area of the country the elders live in and so on. But again and again, he found that differences persisted. For example, Wallace conducted several studies based on data from the 1987 National Medical Expenditure Survey, which included 5,886 people over the age of 65 (1,148 of whom were disabled) who were still living in their community, as well as 4,995 people residing