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

Alzheimers Dement. 2018 Jun;14(6):707-722. doi: 10.1016/j.jalz.2017.11.012. Epub 2018 Jan 6.


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: Alzheimer's disease; Cognitive function; Dementia; General cognitive ability; Lifestyle factors; Metabolites; Metabolomics; NMR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / metabolism
  • Biomarkers / metabolism*
  • Cognitive Dysfunction / metabolism*
  • Cohort Studies
  • Dementia / metabolism*
  • Female
  • Humans
  • Life Style
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Risk Factors


  • Biomarkers