n-3 Fatty acid erythrocyte membrane content, APOE ε4, and cognitive variation: An observational follow-up study in late adulthood

Abstract

Background: Evidence for an inverse relation between dietary intake of n-3 polyunsaturated fatty acids (PUFAs) and age-related cognitive decline is inconsistent. This inconsistency may arise because the relation is present only in the absence of the apolipoprotein E ε4 (APOE ε4) allele. Objective: We aimed to determine the contribution of erythrocyte n-3 PUFA content to cognitive aging in the presence or absence of the APOE ε4 allele. Design: We followed up 120 volunteers, born in 1936, at approximate ages of 64, 66, and 68 y. Their intelligence quotient at 11 y old was available. At first follow-up, we determined APOE genotype and measured the PUFA composition of erythrocyte membranes. Six cognitive tests were administered at all follow-ups. We related cognitive performance at ≈64 y old and cognitive changes from ≈64 to ≈68 y old to erythrocyte n-3 PUFA composition on recruitment and to APOE ε4 allele status. Results: Total n-3 PUFA and docosohexaenoic acid concentrations were associated with benefits for cognition at ≈64 y old and from ≈64 to ≈68 y old. After adjustment for sex, APOE ε4 status, and intelligence quotient at 11 y old, the effects associated with total n-3 PUFA remained significant. Cognitive benefits were associated with higher erythrocyte n-3 PUFA content but were significant only in the absence of the APOE ε4 allele. Conclusions: These data are evidence of a gene x environment interaction for cognitive aging. They are relevant to the analysis of trials of n-3 PUFA supplements in cognitive aging and dementia prevention, and they support heterogeneity in cognitive aging and, possibly, in Alzheimer disease. © 2008 American Society for Nutrition.