Brain Imaging and Alzheimer's Disease

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Alzheimer's Disease Risk Factors

Researchers have developed a new research tool to evaluate factors suggested to increase or decrease the risk of Alzheimer's disease, Eric Reiman, M.D., Scientific Director of the PET Center at Banner Good Samaritan Medical Center in Phoenix, Ariz., and his colleagues reported today in the on-line early edition of Proceedings of the National Academy of Sciences.

The researchers used a brain-imaging technique called positron emission tomography (PET) to measure glucose metabolism, an indicator of brain activity, in healthy adults with three levels of genetic risk for Alzheimer's disease. They found that the greater the risk, the lower the activity in brain regions known to be affected by Alzheimer's.

Alzheimer's disease is the most common form of memory and thinking problems in older persons. It affects about 10 percent of persons over 65 and almost half of those over 85. Community surveys have suggested several genetic and non-genetic factors that may increase a person's risk of Alzheimer's disease, and they have suggested several genetic and non-genetic factors that may reduce a person's risk of Alzheimer's disease. In addition to known genetic factors, for instance, some studies have suggested that higher cholesterol levels may increase the risk of Alzheimer's disease, and some have suggested that certain healthy lifestyle changes, like reducing one's cholesterol levels, taking certain dietary supplements, fish consumption, physical exercise, and mental exercise, might protect a person from developing this disorder.

Unfortunately, traditional surveys have potential limitations. For instance, surveys of older people with and without Alzheimer's disease could be clouded by differences in their ability accurately recall information about potential risk factors like their prior physical fitness level or dietary supplement use. Conversely, surveys of younger people who differ in their fitness level or dietary supplement use might require thousands or research volunteers and many years to determine any effect on their risk of subsequent memory and thinking problems.

The new study compared PET measurements of brain activity in 160 healthy people with no copies, one copy, and two copies of the apolipoprotein E4 (apoE4) gene, a gene which is known to increase a person's Alzheimer's risk and is found about one-fourth of the population. Previous studies have shown a strong relationship between a person's number of apoE4 copies and his or her risk of the disorder. Although people at these three levels of genetic risk for Alzheimer's disease did not differ in any of their memory or thinking abilities, each additional copy of the apoE4 gene was associated with lower brain activity in and only in brain regions that are affected in patients with the clinical diagnosis of Alzheimer's disease.

"Our findings suggest how brain imaging techniques could be used in healthy people to help identify factors which increase or decrease a person's risk for developing Alzheimer's disease," said Reiman, who is also Professor of Psychiatry at the University of Arizona, Clinical Director of the Translational Genomics Research Institute, and Director of the Arizona Alzheimer's Disease Consortium. "They also suggest how brain imaging techniques and other laboratory tests might be used in the future to help evaluate factors which increase or decrease a person's risk for other neurological or psychiatric disorders."

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The researchers believe their approach could be used to test other suggested modifiers of Alzheimer's risk. Factors that increase a person's risk should be associated with decreased brain activity in the Alzheimer's areas, whereas factors that decrease a person's risk should be associated with higher brain activity in those locations.

Reiman and his colleagues are now using PET to evaluate several suggested genetic and non-genetic factors that may influence the risk of Alzheimer's disease, and they continue to follow the people described in today's report to further characterize the risk factors and brain changes that most strongly predict the subsequent development of memory and thinking problems.

Meantime, Reiman cautions that PET and apoE4 testing should not be used clinically as screening devices to assess a healthy person's risk of Alzheimer's disease, since they cannot yet predict with sufficient certainty whether or when a person might develop symptoms of this catastrophic disorder.

Previous studies led by Reiman, which involved a much smaller number of research volunteers and were published in the New England Journal of Medicine and the Proceedings of the National Academy of Sciences, found that healthy carriers of the apoE4 gene had abnormally low brain activity in the same brain regions as clinically affected patients, even in young adulthood. They also suggested how PET could be used to test ways to prevent Alzheimer's disease without having to wait to see if people in the prevention study went on to develop memory and thinking problems.

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The Arizona Alzheimer's Disease Consortium, which includes the state-supported Arizona Alzheimer's Disease Research Center and the National Institute on Aging-sponsored Arizona Alzheimer's Disease Core Center, is a statewide research laboratory without walls dedicated to the scientific understanding, early detection, treatment, and prevention of Alzheimer's disease. - PHOENIX (May 30, 2005)

This study was supported by grants from the National Institute of Mental Health, the National Institute on Aging, and the state of Arizona.

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