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.

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.

• Authors: 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 Lehtimäki, Mika 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
• Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement) Vol. 14 Issue 6 Pg. 723-733 (06 2018) ISSN: 1552-5279 [Electronic] United States
• PMID: 29519576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Amino Acids, Branched-Chain
• Biomarkers
• Lipoproteins

Topics

• Adult
• Aged
• Alzheimer Disease (metabolism, pathology)
• Amino Acids, Branched-Chain (metabolism)
• Biomarkers (metabolism)
• Dementia (metabolism, pathology)
• Humans
• Lipoproteins (metabolism)
• Magnetic Resonance Imaging
• Mass Spectrometry
• Metabolomics (methods)
• Middle Aged
• Prospective Studies
• Risk Assessment
• Risk Factors