Income, diet, and cognitive function: observational analyses and candidate metabolomic pathways identified by Mendelian randomization

BACKGROUND: Household income has been shown to have impact on cognitive function, with dietary patterns and gut microbiota-related metabolic pathways potentially acting as mediating pathways. Our study integrates observational analyses and Mendelian randomization (MR) to explore these associations. METHODS: The observational analysis included 13,457 participants from the UK Biobank who experienced cognitive transitions. A multistate Markov model was applied to assess the effect of income level on cognitive trajectory, while mediation analysis and quantile regression were performed using baseline data. We applied a two-sample, two-step MR approach utilizing genetic instruments from the IEU Open genome-wide association studies (GWAS) project to determine the causal effects of income on cognition, and further estimate the mediating roles of dietary patterns and 1400 gut metabolites linking income with cognitive performance. RESULTS: Over a median follow-up of 8.96 years, a total of 14,040 cognitive transitions were recorded (7429 deterioration events and 6801 improvements), with higher income associated with a lower risk of cognitive deterioration. MR analyses confirmed a causal relationship between income and cognitive performance (OR: 2.140, 95% CI: 1.923-2.381; P < 0.001). Notably, cheese and coffee intake demonstrated significant mediation effects in both observational and two-way, two-step MR. The protective effect of cheese appeared to be mediated by gut metabolites, particularly via tryptophan/tyrosine and carnitine/ergothioneine. CONCLUSIONS: Our findings indicate a significant link between income and cognitive performance, cheese and dried fruit may mediate this protective effect through amino acid and carnitine metabolism pathways. Interventions targeting dietary patterns have the potential to prevent cognitive decline attributable to low income.