Circulating metabolomic profile links the MIND diet to cognitive function in middle-aged and older adults

Abstract The Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet has been related to lower risk of dementia. However, to which extent circulating metabolite profile of this diet mediates the association was unclear. We identified 70 circulating metabolites significantly associated with the MIND diet score in Whitehall II study, and replicated 44 of these associations in the UK Biobank. Docosahexaenoic acid (DHA), omega-3 fatty acids, unsaturation degree of fatty acids and high-density lipoprotein particle size showed the strongest positive associations and very-low-density lipoprotein particle size, glycoprotein acetyls and phenylalanine showed the strongest inverse associations. The metabolic signature constructed from the identified metabolites using elastic net regression was moderately correlated with MIND diet score (Pearson’s r = 0.34 in Whitehall II and 0.25 in UK Biobank). The associations of the MIND diet with global and domain-specific cognitive function were partially mediated by the metabolite signature (explainable proportion ranging from 24–36%).