Abstract P505: Midlife Cognitive Function is Associated With Gut Microbial Species and Metabolic Pathways: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: The gut microbiota may play a role in cognitive function and decline. Animal models support mechanisms involving short-chain fatty acid production, amino acid metabolism, and purine metabolism. There is need to replicate these findings in population-based human studies. Methods: Data were from 570 participants who attended the Yr. 30 follow-up exam (2015-16, ages 48-60 y, 45%:55% Black:White race, 45%:55% M:F sex), provided a fecal sample, and completed a cognitive battery of 6 assessments: Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Rey-Auditory Verbal Learning Test (RAVLT), Stroop, and Letter and Category Fluency. A global cognition score was derived from the 6 assessments using principal components analysis. Species and metabolic pathways were assigned to whole-metagenomics sequence data using standard reference databases. Multivariable-adjusted linear regression was used to test associations between distinct microbial features and measures of cognition, controlling for false discovery rate (FDR). Results: Sequence data mapped to 106 species and 312 metabolic pathways. In multivariable-adjusted regression analysis, adjusted for socio-demographics, health behaviors, and BMI, 5 species and 5 metabolic pathways were significantly associated with measures of cognitive function, FDR < 0.20 (Figure) . These species/pathways are involved in purine and pyrimidine metabolism and short-chain fatty acid production. Conclusion: Identified pathways play a role in neurodevelopment and in the gut-brain axis of physiologic communications. Our findings suggest long-term relationships between gut microbiota composition and cognitive function.