Urinary metabolomics data and cognitive performance in an adult population

With an ageing population, the social and economic burden of cognitive decline is increasing. Urinary metabolomics may offer a promising approach for identifying metabolic markers for early cognitive impairment and gaining insights into underlying biological mechanisms. The aim of this study was to investigate the association between urinary metabolites and cognitive performance in a population-based sample. Cognitive performance was assessed in 560 (digit span) and 553 participants (semantic verbal fluency) of the Metabolism, Nutrition and Immune System in Augsburg (MEIA) study. Urinary concentrations of 51 metabolites were quantified via ¹H nuclear magnetic resonance and normalized to creatinine (Nightingale Health, Finland). Overall and sex-specific associations between metabolites and cognitive outcomes were examined using multivariable linear regression models adjusted for demographic, lifestyle, and health-related confounders. Five metabolites were significantly associated with digit span performance: 3-hydroxyhippurate, trans-aconitate, and uracil in the overall sample, and taurine and pyroglutamate in men only. Eight metabolites were associated with verbal fluency, six of which were observed in the full cohort, namely, acetate, citrate, hippurate, pyroglutamate, taurine, and xanthosine, while glutamine showed associations exclusively in men and propylene glycol exclusively in women. After adjustment for multiple testing, none of the associations remained significant. Urinary metabolites related to energy, microbial, amino acid, and nucleotide metabolism showed domain- and sex-specific associations with cognitive performance. These exploratory findings point towards a potential involvement of systemic metabolic processes related to mitochondrial energy production, oxidative stress, inflammation, and neurotransmission, during early cognitive changes in the general population.