Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies

Abstract

Abstract Introduction Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. Methods We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. Results We discovered and replicated 15 metabolites associated with cognition including subfractions of high‐density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E ( APOE ) genotypes. Six of the cognition‐associated metabolites were related to the risk of dementia and lifestyle factors. Discussion Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia.

Keywords

Affiliated Institutions

• Centre Hospitalier Universitaire de Lille FR
• Universitätsmedizin Greifswald DE
• Tampere University Hospital FI
• The University of Texas Health Science Center at San Antonio US
• Centre de recherche en Epidémiologie et Santé des Populations FR
• Leiden University Medical Center NL
• University College London GB
• Netherlands Metabolomics Centre NL
• University of Bonn DE
• Boston University US
• University of Cologne DE
• Leiden University NL
• Erasmus MC NL
• German Center for Neurodegenerative Diseases DE
• Tampere University FI
• Zimmer Biomet (Germany) DE
• Inserm FR
• Institute for Molecular Medicine Finland FI
• Beth Israel Deaconess Medical Center US
• University Hospital Bonn DE
• Institut Pasteur de Lille FR
• Finnish Institute for Health and Welfare FI
• Amsterdam Neuroscience NL
• University of Helsinki FI
• Amsterdam UMC Location Vrije Universiteit Amsterdam NL
• Vrije Universiteit Amsterdam NL
• University of Tartu EE

Related Publications