Excess Calorie Intake a Risk Factor for Alzheimer?

Summarized by Robert W. Griffith, MD
October 25, 2002 (Reviewed: October 19, 2004)

Introduction

Keeping mice and rats on a restricted calorie diet increases their lifespan; this is probably because oxidative damage is reduced. Reactive oxygen species are known to increase deposition of amyloid beta in brain tissue by oxidation of protein and/or DNA, and by lipid peroxidation. This led scientists at Columbia University, New York, to examine the possible effects of dietary intake on the development of Alzheimer disease. The results of this study have been reported in the Archives of Neurology, and are summarized here.

Method

A random sample of healthy Medicare beneficiaries living in northern Manhattan was invited to participate. On entry they had a structured interview, full medical history, physical exam (including a neurological exam), and a neuropsychological battery of tests. These examinations were repeated annually. During the first year participants completed a food frequency questionnaire administered by telephone.

Alzheimer disease was diagnosed by a consensus of specialists, who met at baseline and again annually. Criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were used.

Using information from the questionnaires, total caloric intake was measured in kilocalories per day. Carbohydrates, fats and protein were measured in grams per day, and adjusted for total caloric intake. Quartiles were created for caloric and macronutrient intakes.

Participants were assigned to one of 3 ethnic groups: black, Hispanic, or white. Apolipoprotein E (APOE) genotyping led to classification of participants as 'positive' if they had one or more APOE e4 alleles.

Results

A total of 980 subjects were studied over 4 years. Their mean age was 75.3 years; 67% were women, and 25% white, 43% Hispanic, and 32% black. 28% were APOE e4 positive (i.e. homozygous or heterozygous). There were 242 cases of incident Alzheimer disease during the study period.

The hazards ratios (HR) for Alzheimer disease for people in each quartile of caloric intake, with the lowest as 1.0, were calculated, adjusted for age, sex, APOE positiveness, years of education, and ethnic group. For the second, third, and highest quartile, they were 1.21, 1.20, and 1.48 (95% CI, 1.00-2.19). Thus, compared with subjects in the lowest quartile, those in the highest quartile had a significantly increased risk of Alzheimer disease.

The HRs for Alzheimer's for subjects in the same quartiles for daily fat intake were: 1.46, 1.56, and 1.41; only the third quartile was significantly different from the first (95%CI, 1.05-2.33).

Analyses were done to determine if the associations seen between total caloric and fat intake and Alzheimer disease were different for APOE positive and APOE negative subjects. This proved to be the case. The HRs for Alzheimer disease for the highest quartiles of calories and fat intake were 2.27 (95%CI, 1.11-4.68) and 2.31 (95%CI, 1.09-4.89), respectively. The corresponding HRs for subjects without the APOE e4 allele were 1.06 and 1.15 respectively (both values non-significant).

Comment

This study shows that higher intake of calories and fats are associated with a higher risk of Alzheimer disease in people carrying the APOE e4 allele. The authors point out that an earlier study conducted with younger subjects (lower age limit 55 years) reported an association between higher fat intake and Alzheimer disease over a two-year period. And it is known that people with APOE e4 alleles metabolize lipids differently from non-carriers.

Studies of interactions between diet and genes are a relatively recent development, but, as this one shows, they may prove important in helping determine the best preventive management strategies. The new field of 'nutrigenomics' will provide further examples where dietary recommendations will depend on genetic testing.

While the present study shows no association between caloric and fat intake with Alzheimer disease in non-carriers of APOE e4 (i.e. three-quarters of the population), there is no doubt that limiting calories and fat in the diet would benefit most middle-aged and senior adults, without consideration of their genetic make-up.

Source

• Caloric intake and the risk of Alzheimer disease. JA. Luchsinger, M-X. Tang, S. Shea,  et al., Arch Neurol, 2002, vol. 59, pp. 1528--1563

Related Links
Genetics of Alzheimer Disease - Updated
Antioxidants Shown to Reduce Alzheimer's Risk
Cholesterol Tied to Cognitive Function in Elderly

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