Metabolic pathways associated with cardiometabolic risk effects on cognition in middle-aged adults: the CARDIA study

Sujin Kang; Timothy Ebbels; Queenie Chan; Luke Whiley; Elaine Holmes; Kristine Yaffe; Katie Meyer; Julian Griffin

doi:10.1007/s11306-026-02458-w

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Metabolic pathways associated with cardiometabolic risk effects on cognition in middle-aged adults: the CARDIA study

Journal article

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Metabolic pathways associated with cardiometabolic risk effects on cognition in middle-aged adults: the CARDIA study

Sujin Kang, Timothy Ebbels, Queenie Chan, Luke Whiley, Elaine Holmes, Kristine Yaffe, Katie Meyer and Julian Griffin

Metabolomics, Vol.22(4), 99

2026

DOI: https://doi.org/10.1007/s11306-026-02458-w

PMID: 42307870

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Abstract

Blood Glucose - metabolism

Brain - diagnostic imaging

Brain - metabolism

Cardiometabolic Risk Factors

Cardiovascular Diseases - metabolism

Cognition - physiology

Female

Humans

Magnetic Resonance Imaging

Male

Metabolic Networks and Pathways

Middle Aged

Background Evidence 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. Methods Data 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. Results Fasting 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. Conclusions Urinary 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.

Details

Title: Metabolic pathways associated with cardiometabolic risk effects on cognition in middle-aged adults: the CARDIA study
Authors/Creators: Sujin Kang - Imperial College London
Timothy Ebbels - Imperial College London
Queenie Chan - Imperial College London
Luke Whiley - Curtin University
Elaine Holmes - Imperial College London
Kristine Yaffe - University of California, San Francisco
Katie Meyer - University of North Carolina at Chapel Hill
Julian Griffin - University of Aberdeen
Publication Details: Metabolomics, Vol.22(4), 99
Publisher: Springer
Identifiers: 991005896087307891
Murdoch Affiliation: Centre for Computational and Systems Medicine
Language: English
Resource Type: Journal article

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