n-3 Fatty acid erythrocyte membrane content,: an observational follow-up study in late adulthood1-3APOE ε: an observational follow-up study in late adulthood1-34, and cognitive variation: an observational follow-up study in late adulthood1-3

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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.


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.


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.


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.


These data are evidence of a gene × 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.

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