n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood

Am J Clin Nutr. 2008 Feb;87(2):449-54. doi: 10.1093/ajcn/87.2.449.

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 epsilon4 (APOE epsilon4) 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 epsilon4 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 approximately 64 y old and cognitive changes from approximately 64 to approximately 68 y old to erythrocyte n-3 PUFA composition on recruitment and to APOE epsilon4 allele status.

Results: Total n-3 PUFA and docosohexaenoic acid concentrations were associated with benefits for cognition at approximately 64 y old and from approximately 64 to approximately 68 y old. After adjustment for sex, APOE epsilon4 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 epsilon4 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / metabolism*
  • Apolipoprotein E4 / metabolism*
  • Cognition*
  • Erythrocyte Membrane / metabolism*
  • Fatty Acids, Omega-3 / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged

Substances

  • Apolipoprotein E4
  • Fatty Acids, Omega-3