Abstracts & Commentary
Synopsis: Compared with individuals in the lowest quartile of caloric intake, those in the highest quartile had an increased risk of AD, which showed a hazard ratio of 1.5.
Sources: Luchsinger JA, et al. Arch Neurol. 2002;59:1258-1263; Roth GS, et al. Science. 2002;297:811.
There is evidence that diet could play a role in Alzheimer's disease (AD) risk. Caloric intake has been shown to affect aging in animals and, possibly, in humans. Caloric restriction in mice and rats increases average and maximum life span possibly by decreasing oxidative damage. The balance of macronutrients in diet may also affect oxidative stress unrelated to total caloric intake. There is increasing evidence that oxidative damage may increase beta-amyloid deposition as well as the intracellular accumulation beta-amyloid 1-42.
In the present epidemiologic study, 980 individuals free of dementia at baseline were followed for a mean of 4 years. The daily intake of calories, carbohydrates, fats, and proteins were recalled using a semi-quantitative food frequency questionnaire that was administered between baseline and the first follow-up visits. Luchsinger and colleagues subsequently examined the risk of AD between quartiles of intake after adjusting for confounders. They found 242 incident cases of AD during the 4023 years of follow-up. Compared with individuals in the lowest quartile of caloric intake, those in the highest quartile had an increased risk of AD, which showed a hazard ratio of 1.5. In individuals with apolipoprotein E epsilon4 allele, the hazard ratios of AD for the highest quartile of caloric or food intake were 2.3 as compared to the lowest quartiles. In individuals who did not have the apoliprotein E epsilon4 allele, there was no significant effect of caloric intake or fat intake on AD risk.
Comment by M. Flint Beal, MD
The main limitation of this study pertains to the measure of nutrient intake. The food frequency questionnaire measures habitual intake during 1 year and does not account for day-to-day variation or longer-term periods of intake. In addition, the measures obtained from the semi-quantitative food frequency questionnaire may not have sufficient precision to make inferences about absolute levels of nutrient intake. Nevertheless, the findings are of interest. This is due to the abundant literature which shows that reduced caloric intake has neuroprotective effects in animal models of neurotoxicity. Reduced caloric intake may reduce oxidative stress and increase both average and maximum lifespan. The relevance of this for normal human aging has recently been shown in a report in Science that biomarkers of caloric restriction may predict longevity in humans. In the NIA primate aging study of male rhesus monkeys, caloric restriction resulted in a slightly lower body temperature, reduced insulin levels, and slowed the rate of decline in serum dehydroepiandrosterone sulfate. In the Baltimore longitudinal study of aging in male humans, it was demonstrated that all 3 of these markers showed significant effects on survival. Consistent with beneficial effects of caloric restriction on aging and life span in other animals, individuals with lower temperature and insulin, and those maintaining higher dehydroepiandrosterone sulfate levels had longer survival than their respective counterparts.
These findings both in AD as well as in normal humans suggest that a number of markers associated with caloric restriction may predict increased longevity and reduce incidence of AD. Further studies of these interactions are warranted.
Dr. Beal is Professor and Chairman; Department of Neurology; Cornell University Medical College, New York, NY.
There is evidence that diet could play a role in Alzheimer's disease (AD) risk. This epidemiologic study examined the risk of AD between quartiles of calorie, carbohydrate, fat, and protein intake after adjusting for confounders.
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