Abstract

Dietary patterns are associated with dementia risk, but the underlying molecular mechanisms are largely unknown. We used RNA sequencing data from post mortem prefrontal cortex tissue and annual cognitive evaluations from 1204 participants in the Religious Orders Study and Memory and Aging Project. We identified a transcriptomic profile correlated with the MIND diet (Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay) among 482 individuals who completed ante mortem food frequency questionnaires; and examined its associations with cognitive health in the remaining 722 participants. We identified a transcriptomic profile, consisting of 50 genes, correlated with the MIND diet score (p=0.001). Each standard deviation increase in the transcriptomic profile score was associated with a slower annual rate of decline in global cognition (β=0.011, p=0.003) and lower odds of dementia (odds ratio=0.76, p=0.0002). Expressions of several genes (including TCIM and IGSF5) appeared to mediate the association between MIND diet and dementia. A brain transcriptomic profile for healthy diets revealed novel genes potentially associated with cognitive health. Why healthy dietary patterns are associated with lower dementia risk are unknown. We integrated dietary, brain transcriptomic, and cognitive data in older adults. Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet intake is correlated with a specific brain transcriptomic profile. This brain transcriptomic profile score is associated with better cognitive health. More data are needed to elucidate the causality and functionality of identified genes.

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