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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(s) -
Tynkkynen Juho,
Chouraki Vincent,
Lee Sven J.,
Hernesniemi Jussi,
Yang Qiong,
Li Shuo,
Beiser Alexa,
Larson Martin G.,
Sääksjärvi Katri,
Shipley Martin J.,
SinghManoux 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,
AlaKorpela Mika,
Vasan Ramachandran S.,
Kivimäki Mika,
Duijn Cornelia M.,
Seshadri Sudha,
Salomaa Veikko
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.01.003
Subject(s) - dementia , lipoprotein , cholesterol , medicine , alzheimer's disease , endocrinology , very low density lipoprotein , disease
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.