Long-chain omega3 polyunsaturated fatty acids and cognition in older people: interaction with APOE genotype

Abstract

Basic research and epidemiological studies suggest a protective effect of long-chain omega3 polyunsaturated fatty acids (LC n-3 PUFA) against age-related cognitive decline. However, most randomized controlled trials with LC n-3 PUFA supplements have yielded disappointing results on cognitive outcomes in older persons. One explanation for this discrepancy may be an inadequate targeting of potential beneficiaries of LC n-3 PUFA according to their Apolipoprotein E (APOE) genotype. The aim of this paper was to examine the potential modifying effect of APOE genotype on LC n-3 PUFA metabolism and its relation to cognitive decline in older persons. At least five epidemiological studies and three intervention studies with LC n-3 PUFA supplements have found an interaction between LC n-3 PUFA and APOE genotype on cognition. However, the direction of the effect is inconsistent across studies: the impact of LC n-3 PUFA on cognition is stronger in APOE4 carriers (the main genetic risk factor for Alzheimer’s disease) in some studies, but conversely stronger in APOE4 non-carriers in other studies. These discordant results may be explained by different age groups, cognitive status, measures of cognition, or amounts of DHA intake across studies. Experimental studies suggest that the APOE4 genotype modifies the metabolism of DHA. The APOE genotype should be systematically taken into account and interactions tested in epidemiological and intervention studies with LC n-3 PUFA. Further research is needed to better understand the underlying mechanisms of this gene X diet interaction.

Keywords

• Cognition
• aging
• omega3 fatty acids
• Apolipoprotein E gene
• DHA