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

Show full item record



Permalink

http://hdl.handle.net/10138/236767

Citation

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 , Lehtimäki , T , Kähönen , M , Perola , M , Metspalu , A , Kangas , A J , Soininen , P , Ala-Korpela , M , Vasan , R S , Kivimäki , M , van Duijn , C M , Seshadri , S & 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 & Dementia , vol. 14 , no. 6 , pp. 723-733 . https://doi.org/10.1016/j.jalz.2018.01.003

Title: 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
Author: Tynkkynen, Juho; Chouraki, Vincent; van der Lee, Sven J.; Hernesniemi, Jussi; Yang, Qiong; Li, Shuo; Beiser, Alexa; Larson, Martin G.; Sääksjärvi, Katri; Shipley, Martin J.; Singh-Manoux, Archana; Gerszten, Robert E.; Wang, Thomas J.; Havulinna, Aki S.; Würtz, Peter; Fischer, Krista; Demirkan, Ayse; Ikram, M. Arfan; Amin, Najaf; Lehtimäki, Terho; Kähönen, Mika; Perola, Markus; Metspalu, Andres; Kangas, Antti J.; Soininen, Pasi; Ala-Korpela, Mika; Vasan, Ramachandran S.; Kivimäki, Mika; van Duijn, Cornelia M.; Seshadri, Sudha; Salomaa, Veikko
Contributor: University of Helsinki, Complex Disease Genetics
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Clinicum
Date: 2018-06
Language: eng
Number of pages: 11
Belongs to series: Alzheimer's & Dementia
ISSN: 1552-5260
URI: http://hdl.handle.net/10138/236767
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. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
Subject: Dementia
Alzheimer's disease
Metabolomics
Biomarkers
Amino acids
COGNITIVE IMPAIRMENT
PROGRESSION
GLUTAMATE
PLASMA
VLDL
METABOLOMICS
RECEPTOR
MARKERS
IMPACT
BRAIN
3112 Neurosciences
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S1552526018300207_main.pdf 606.7Kb PDF View/Open
1_s2.0_S1552526018300207_main.pdf 656.0Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record