Genetic modifiers of the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) response

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ABSTRACT Age-associated cognitive decline varies in extent among individuals, and this variation likely arises from a complex interplay of genetic and environmental factors. The Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) is based on the most compelling evidence in the diet-dementia field. Epidemiological data suggest that greater adherence to the MIND diet slows the rate of cognitive decline and reduces the risk of Alzheimer's disease (AD). Genome-wide association studies of AD are enriched with variants mapping to genes implicated in immune response and cholesterol metabolism, which may result in different responses to preventive measures such as diet. Foods and nutrients emphasized by MIND have also been shown to have beneficial effects on the brain, potentially mediated by immunity or cholesterol pathways. Genetic factors contributing to between-person variation in metabolism of key MIND components may also enhance or limit their efficacy and ultimately impact response to this diet. MIND associations with cognitive health are modest overall but, when combined with individual genetic information concerning AD susceptibility and MIND-component metabolism, may reveal subgroups of the population who especially benefit when adhering to this diet. Our proposal leverages the first, ongoing MIND trial as well as existing community- and population-based data to examine how genetic differences in (a) AD predisposition and (b) nutrient metabolism modify the response to the MIND diet. Our research will provide mechanistic insights into the role that MIND may play in slowing cognitive decline and will also inform the implementation of MIND for optimal effectiveness.