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.

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Keywords Alzheimer's disease, Cognitive function, Dementia, General cognitive ability, Lifestyle factors, Metabolites, Metabolomics, NMR
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Journal Alzheimer's & Dementia
van der Lee, S.J, Teunissen, C.E, Pool, R, Shipley, M.J, Teumer, A, Chouraki, V. (Vincent), … van Duijn, C.M. (2018). Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies. Alzheimer's & Dementia. doi:10.1016/j.jalz.2017.11.012