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Basic research and epidemiological studies suggest a protective effect of long-chainomega3 polyunsaturated fatty acids (LC n-3 PUFA) against age-related cognitive decline.However, most randomized controlled trials with LC n-3 PUFA supplements have yieldeddisappointing results on cognitive outcomes in older persons. One explanation for thisdiscrepancy may be an inadequate targeting of potential beneficiaries of LC n-3 PUFAaccording to their Apolipoprotein E (APOE) genotype. The aim of thispaper was to examine the potential modifying effect of APOE genotype onLC n-3 PUFA metabolism and its relation to cognitive decline in older persons. At leastfive epidemiological studies and three intervention studies with LC n-3 PUFA supplementshave found an interaction between LC n-3 PUFA and APOE genotype oncognition. However, the direction of the effect is inconsistent across studies: the impactof LC n-3 PUFA on cognition is stronger in APOE4 carriers (the maingenetic risk factor for Alzheimer’s disease) in some studies, but conversely stronger inAPOE4 non-carriers in other studies. These discordant results may beexplained by different age groups, cognitive status, measures of cognition, or amounts ofDHA intake across studies. Experimental studies suggest that the APOE4genotype modifies the metabolism of DHA. The APOE genotypeshould be systematically taken into account and interactions tested in epidemiological andintervention studies with LC n-3 PUFA. Further research is needed to better understand theunderlying mechanisms of this gene X diet interaction

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