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.
Highlights
Alzheimer’s disease (AD) is the main cause of cognitive decline and dementia in older persons (Cummings, 2004)
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 Apolipoprotein E (APOE) genotype on cognition
The direction of the effect is inconsistent across studies: the impact of LC n-3 PUFA on cognition is stronger in APOE4 non-carriers in some studies, but stronger in APOE4 carriers in other studies
Summary
Alzheimer’s disease (AD) is the main cause of cognitive decline and dementia in older persons (Cummings, 2004). AD is characterized by the progressive accumulation of beta-amyloide (Abeta) peptide in senile plaques and hyperphosphorylated tau protein in neurofibrillary tangles These neurodegenerative lesions are accompanied by increased oxidative stress, inflammation, and neuronal death leading to brain atrophy and cognitive decline (Querfurth and LaFerla, 2010). Most randomized controlled trials (RCT) with LC n-3 PUFA supplements have been disappointing regarding cognitive outcomes in older persons (Jiao et al, 2014). One explanation for this discrepancy may be an inadequate targeting of potential beneficiaries of LC n-3 PUFA according to their APOE genotype (Barberger Gateau, Samieri, et al, 2013). The aim of this narrative review was to examine the potential modifying effect of APOE genotype on LC n-3 PUFA metabolism and its relation to AD and cognitive decline in older persons
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