Characterization of a metabolomics signature of the brain-health-promoting MIND diet in older persons.

BACKGROUND: The MIND diet supports healthy cognitive aging. Yet, a challenge remains to identify individuals who do not adhere to the MIND and could be at risk for accelerated cognitive decline. A multi-metabolite biomarker panel could facilitate population screening. OBJECTIVES: To determine and validate a blood metabolomics signature of MIND adherence in a large cohort of older adults, and to estimate its association with subsequent cognitive decline. DESIGN, SETTING AND PARTICIPANTS: Participants were older adults (≥65 years) from the population-based three-City (3C) cohort, free of dementia at study baseline and followed for up to 12 years for cognition, who were included in two case-control samples on cognitive decline nested within two centers (Bordeaux and Dijon cities, n = 838). EXPOSURES: 155 diet-related serum metabolites measured with a multianalyte metabolomics platform. MAIN OUTCOMES AND MEASUREMENTS: The primary outcome was adherence to the MIND diet, assessed in a subsample of 344 participants from Bordeaux center (which underwent the dietary surveys, 24 h recall and food-frequency questionnaire). A metabolomics signature of MIND diet adherence was characterized with penalized regression and a metabolomics score ("metaboscore") reflecting the overall MIND biological fingerprint was calculated. The secondary outcome was cognitive decline status (coded as binary: accelerated, vs. null or minimal decline) over follow-up, assessed using repeated cognitive measures in the two case-control samples. The metaboscore was reconstructed and linked to the odds of cognitive decline. RESULTS: Eight metabolites were identified: three were associated with higher MIND adherence (3-hydroxyhippuric acid, 5-hydroxyindole-3-acetic acid, betaine - phenolic acids and amino acid related to plant foods) and five with lower MIND adherence (1-methylhistidine from red meat; cyclo(L-leucyl-L-prolyl) from coffee; tartaric acid from wine; myristoyl-carnitine and dehydroepiandrosterone sulfate, endogenous). The French-MIND metaboscore was linked to lower odds of cognitive decline, although replication was not statistically significant after multivariable adjustment. CONCLUSION: A novel metabolomic signature of the MIND diet was characterized, which may help screen older adults at risk of poor brain nutrition and could support personalized dietary prevention strategies.