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n–3 Fatty acid erythrocyte membrane content, APOE 4, and cognitive variation: an observational follow-up study in late adulthood^1,2,3

¹ From the Department of Environmental and Occupational Medicine, University of Aberdeen, Aberdeen, United Kingdom (LJW and HCF); the Department of Psychology (IJD) and the Department of Geriatric Medicine, Royal Victoria Hospital (JMS), University of Edinburgh, Edinburgh, United Kingdom; the Department of Life Sciences, Robert Gordon University, Aberdeen, United Kingdom (KWW); Vascular Health, Rowett Research Institute, Aberdeen, United Kingdom (KAR); and the Department of Psychology, University of Dundee, Dundee, United Kingdom (VJB)

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 4 (APOE 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 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 64 y old and cognitive changes from 64 to 68 y old to erythrocyte n–3 PUFA composition on recruitment and to APOE 4 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 4 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 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.

Key Words: Polyunsaturated fatty acids • erythrocytes • cognitive decline • fish-oil consumption • apolipoprotein E • childhood intelligence • cognitive tests

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