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

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 epsilon 4 (APOE epsilon 4) 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 epsilon 4 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 approximate to 64 y old and cognitive changes from approximate to 64 to approximate to 68 y old to erythrocyte n-3 PUFA composition on recruitment and to APOE epsilon 4 allele status. Results: Total n-3 PUFA and docosohexaenoic acid concentrations were associated with benefits for cognition at approximate to 64 y old and from approximate to 64 to approximate to 68 y old. After adjustment for sex, APOE epsilon 4 status, and intelligence quotient at I I 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 epsilon 4 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.