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

Sven J. van der Lee, Charlotte E. Teunissen, René Pool, Martin J. Shipley, Alexander Teumer, Vincent Chouraki, Debora Melo van Lent, Juho Tynkkynen, Krista Fischer, Jussi Hernesniemi, Toomas Haller, Archana Singh-Manoux, Aswin Verhoeven, Gonneke Willemsen, Francisca A. de Leeuw, Holger Wagner, Jenny van Dongen, Johannes Hertel, Kathrin Budde, Ko Willems van DijkLeonie Weinhold, M. Arfan Ikram, Maik Pietzner, Markus Perola, Michael Wagner, Nele Friedrich, P. Eline Slagboom, Philip Scheltens, Qiong Yang, Robert E. Gertzen, Sarah Egert, Shuo Li, Thomas Hankemeier, Catharina E.M. van Beijsterveldt, Ramachandran S. Vasan, Wolfgang Maier, Carel F.W. Peeters, Hans Jörgen Grabe, Alfredo Ramirez, Sudha Seshadri, Andres Metspalu, Mika Kivimäki, Veikko Salomaa, Ayşe Demirkan, Dorret I. Boomsma, Wiesje M. van der Flier, Najaf Amin, Cornelia M. van Duijn

Research output: Contribution to journalArticleAcademicpeer-review

106 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)707-722
Number of pages16
JournalAlzheimers & Dementia
Issue number6
Early online date6 Jan 2018
Publication statusPublished - Jun 2018


  • Alzheimer's disease
  • Cognitive function
  • Dementia
  • General cognitive ability
  • Lifestyle factors
  • Metabolites
  • Metabolomics
  • NMR

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