Comment: Gene-environment interactions in dementia-: Not just another fish story.

Abstract

Many observational studies have shown relationships between dietary omega-3 fatty acids and cognitive outcomes, but relatively few have examined gene–environment interactions due to APOE genotype. In this study, van de Rest et al.1 highlight the modifying effect of APOE genotype on cognitive effects of dietary omega-3 fatty acids, finding “protective” effects of dietary seafood/omega-3s only in the e4 carrier group, which is at higher risk of Alzheimer disease. Prior observational studies that have incorporated APOE genotype have reported mixed results, sometimes concluding that the omega-3 benefit is stronger in the e4 carriers and sometimes in the e4 noncarriers. The finding in the present study is strengthened by a recent report from the same group showing an inverse relationship between dietary omega-3 and autopsy-confirmed Alzheimer disease brain pathology, also only in e4 carriers.2 However, observational studies and clinicopathologic studies cannot determine with certainty whether dietary or supplemental omega-3s will attenuate cognitive decline in individuals at risk. Randomized, placebo-controlled trials are necessary to definitively answer this question. While most of these have been negative,3 few have included APOE stratification in the analyses, so may have failed to appreciate genotype-specific effects of omega-3 supplementation.