Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts

Juho Tynkkynen, Vincent Chouraki, Sven J. van der Lee, Jussi Hernesniemi, Qiong Yang, Shuo Li, Alexa Beiser, Martin G. Larson, Katri Sääksjärvi, Martin J. Shipley, Archana Singh-Manoux, Robert E. Gerszten, Thomas J. Wang, Aki S. Havulinna, Peter Würtz, Krista Fischer, Ayse Demirkan, M. Arfan Ikram, Najaf Amin, Terho LehtimäkiMika Kähönen, Markus Perola, Andres Metspalu, Antti J. Kangas, Pasi Soininen, Mika Ala-Korpela, Ramachandran S. Vasan, Mika Kivimäki, Cornelia M. van Duijn, Sudha Seshadri, Veikko Salomaa

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Introduction: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. Methods: We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Results: Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Discussion: Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology.

Original languageEnglish (US)
Pages (from-to)723-733
Number of pages11
JournalAlzheimer's and Dementia
Volume14
Issue number6
DOIs
StatePublished - Jun 2018
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amino acids
  • Biomarkers
  • Dementia
  • Metabolomics

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Tynkkynen, J., Chouraki, V., van der Lee, S. J., Hernesniemi, J., Yang, Q., Li, S., Beiser, A., Larson, M. G., Sääksjärvi, K., Shipley, M. J., Singh-Manoux, A., Gerszten, R. E., Wang, T. J., Havulinna, A. S., Würtz, P., Fischer, K., Demirkan, A., Ikram, M. A., Amin, N., ... Salomaa, V. (2018). Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts. Alzheimer's and Dementia, 14(6), 723-733. https://doi.org/10.1016/j.jalz.2018.01.003