TY - JOUR
T1 - Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease
T2 - A prospective study in eight cohorts
AU - Tynkkynen, Juho
AU - Chouraki, Vincent
AU - van der Lee, Sven J.
AU - Hernesniemi, Jussi
AU - Yang, Qiong
AU - Li, Shuo
AU - Beiser, Alexa
AU - Larson, Martin G.
AU - Sääksjärvi, Katri
AU - Shipley, Martin J.
AU - Singh-Manoux, Archana
AU - Gerszten, Robert E.
AU - Wang, Thomas J.
AU - Havulinna, Aki S.
AU - Würtz, Peter
AU - Fischer, Krista
AU - Demirkan, Ayse
AU - Ikram, M. Arfan
AU - Amin, Najaf
AU - Lehtimäki, Terho
AU - Kähönen, Mika
AU - Perola, Markus
AU - Metspalu, Andres
AU - Kangas, Antti J.
AU - Soininen, Pasi
AU - Ala-Korpela, Mika
AU - Vasan, Ramachandran S.
AU - Kivimäki, Mika
AU - van Duijn, Cornelia M.
AU - Seshadri, Sudha
AU - Salomaa, Veikko
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amino acids
KW - Biomarkers
KW - Dementia
KW - Metabolomics
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U2 - 10.1016/j.jalz.2018.01.003
DO - 10.1016/j.jalz.2018.01.003
M3 - Article
C2 - 29519576
AN - SCOPUS:85042905746
SN - 1552-5260
VL - 14
SP - 723
EP - 733
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 6
ER -