ArticleMetabolomics : Official journal of the Metabolomic Society2026
Metabolic pathways associated with cardiometabolic risk effects on cognition in middle-aged adults: the CARDIA study.
Article in Metabolomics : Official journal of the Metabolomic Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEvidence increasingly suggests a connection between cardiovascular disease and brain health in later life; however, the mechanistic pathways from human studies remain unclear. This study aimed to investigate whether urinary metabolites account for part of the association between cognition and cardiometabolic risk.
methodsData from 606 participants (aged 48-60; 55% female; 45.5% Black/African American) in the Year 30 follow-up of the Coronary Artery Risk Development in Young Adults Study were analyzed. Urinary metabolites were profiled using nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry; brain magnetic resonance imaging data were available for 281 participants. Structural equation models were used to assess pathways linking cardiometabolic factors to cognitive outcome, with urinary metabolites and brain MRI-derived parameters as mediators.
resultsFasting glucose showed a negative association with cognition. Valine, isoleucine, leucine, and phenylalanine were positively associated with fasting glucose. Valine and aminoadipic acid also showed positive associations between fasting glucose and cognition, while tryptophan was correlated with both fasting glucose and cognition. Indole-3-acetic acid showed negative associations with systolic blood pressure and fasting glucose. Brain MRI-derived parameters in memory-related medial temporal areas were associated with waist circumference.
conclusionsUrinary metabolites and brain imaging markers were linked with hyperglycemia, obesity, and cognitive performance, highlighting multimodal biomarkers relevant to global cognitive function in individuals with cardiometabolic risk.
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