Even Very Old Brains Benefit From Exercise

Results from two new studies provide both bad news and good news on Alzheimer's disease. The disease may start as early as in adolescence, but it may be preventable even up to old age.

The e4 variant of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alzheimer's identified to date. In fact, apart from age, it is the best-documented risk factor for the disease. Although possession of the variant is neither necessary nor sufficient for developing Alzheimer's, individuals who have the variant and develop Alzheimer's succumb to the illness about a decade earlier than do those who have the other two variants of the gene— e2 and e3—and who develop Alzheimer's (Psychiatric News, February 3, 2006).

Moreover, the entorhinal cortex, which lies in front of the hippocampus in both the left temporal lobe and the right temporal lobe and is vital for memory consolidation, is known to be the first brain area to be affected by Alzheimer's. So Philip Shaw, M.D., a research psychiatrist at the National Institute of Mental Health's Child Psychiatry Branch, and his colleagues wondered whether youth who possess the APOE e4 variant might also show signs of a deterioration in the entorhinal cortex.

They decided to assess which APOE gene variants that 239 healthy children and teens possessed, performed MRI scans of their brains, and then compared results from youngsters with the e4 variant with those from youngsters with the two other types.

Youngsters who were e4 carriers had a significantly thinner left entorhinal cortex than did the non-e4 carriers. Youngsters who were e4 carriers also had a thinner right entorhinal cortex than did the non-e4 carriers, but the difference was not statistically significant. Furthermore, there was a significant stepwise increase in thickness of the left entorhinal cortex depending on which APOE gene variant subjects possessed. In other words, the e4 carriers had the thinnest cortex, the e3 carriers a cortex of intermediate thickness, and the e2 carriers the thickest cortex.

Thus the scientists' hypothesis that youth who possess the e4 variant would show signs of a deteriorated entorhinal cortex was largely confirmed.

However, the amount of entorhinal thinning in the e4 group was about 10 times less than that seen in individuals with Alzheimer's, suggesting that those youth who possess such thinning are a long way from actually developing the illness or, in fact, may never get it.

Which raises another question. Might certain lifestyle factors such as exercise help ward off Alzheimer's in persons who carry the e4 variant or other genetic vulnerabilities for the disease? Indeed, it's a possibility. A number of studies have demonstrated an association between participation in physical activity and a decreased risk of Alzheimer's in young-old people, that is, those aged 65 to 75. And now a new investigation has found that even old-old people, those aged 85 or older, may be able to reduce their chances of succumbing to Alzheimer's by exercising, regardless of their APOE gene status.

This study was conducted by Jeffrey Kaye, M.D., Ph.D., and colleagues at Oregon Health and Science University. Sixty-six individuals aged 85 or older were enrolled. The researchers determined that all were cognitively healthy and free of comorbid conditions that might affect cognition. The subjects then gave blood samples to be analyzed for APOE gene status and completed a leisure-activity questionnaire, which included questions about their exercise habits. Kaye and his coworkers then calculated the total amount of exercise each subject engaged in each week. It included the sum of hours spent in either light exercise, such as walking, biking, or golfing, or strenuous exercise, such as jogging, swimming, hiking, or wood splitting.

The subjects were followed for five years to determine whether they developed cognitive impairment, which the researchers defined as repeated abnormal scores on the Mini-Mental State Examination or the Clinical Dementia Rating Scale at two consecutive assessments. The risk of such impairment in this age group is very high; 38 of the 66 subjects, or 57 percent, had developed cognitive impairment by the end of the study.

Kaye and his group did in fact find a link between the amount of exercise subjects had engaged in and whether they developed cognitive impairment, according to the report of their findings in the April Journal of Aging and Health. Even when possibly confounding variables such as age, gender, education, and APOE gene status were taken into consideration, women who exercised more than four hours a week were significantly less likely to develop cognitive impairment than were women who did not exercise that much. The risk of cognitive impairment was also reduced in the men who were more active, but not to a significant degree, perhaps because the sample size was not big enough to detect a difference in this group.

An abstract of “Cortical Morphology in Children and Adolescents With Different Apolipoprotein E Gene Polymorphisms: An Observational Study” can be accessed at<www.thelancet.com/journals/lancet> byclicking on “The Lancet Neurology.” An abstract of “Physical Activity and the Risk of Dementia in the Oldest Old” is posted at<http://jah.sagepub.com/cgi/content/abstract/19/2/242>.▪