Circulating metabolites and general cognitive ability and dementia : Evidence from 11 cohort studies

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van der Lee , S J , Teunissen , C E , Pool , R , Shipley , M J , Teumer , A , Chouraki , V , van Lent , D M , Tynkkynen , J , Fischer , K , Hernesniemi , J , Haller , T , Singh-Manoux , A , Verhoeven , A , Willemsen , G , de Leeuw , F A , Wagner , H , van Dongen , J , Hertel , J , Budde , K , van Dijk , K W , Weinhold , L , Ikram , M A , Pietzner , M , Perola , M , Wagner , M , Friedrich , N , Slagboom , P E , Scheltens , P , Yang , Q , Gertzen , R E , Egert , S , Li , S , Hankemeier , T , van Beijsterveldt , C E M , Vasan , R S , Maier , W , Peeters , C F W , Grabe , H J , Ramirez , A , Seshadri , S , Metspalu , A , Kivimäki , M , Salomaa , V , Demirkan , A , Boomsma , D I , van der Flier , W M , Amin , N & van Duijn , C M 2018 , ' Circulating metabolites and general cognitive ability and dementia : Evidence from 11 cohort studies ' , Alzheimer's & Dementia , vol. 14 , no. 6 , pp. 707-722 . https://doi.org/10.1016/j.jalz.2017.11.012

Title: Circulating metabolites and general cognitive ability and dementia : Evidence from 11 cohort studies
Author: van der Lee, Sven J.; Teunissen, Charlotte E.; Pool, Rene; Shipley, Martin J.; Teumer, Alexander; Chouraki, Vincent; van Lent, Debora Melo; Tynkkynen, Juho; Fischer, Krista; Hernesniemi, Jussi; Haller, Toomas; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francisca A.; Wagner, Holger; van Dongen, Jenny; Hertel, Johannes; Budde, Kathrin; van Dijk, Ko Willems; Weinhold, Leonie; Ikram, M. Arfan; Pietzner, Maik; Perola, Markus; Wagner, Michael; Friedrich, Nele; Slagboom, P. Eline; Scheltens, Philip; Yang, Qiong; Gertzen, Robert E.; Egert, Sarah; Li, Shuo; Hankemeier, Thomas; van Beijsterveldt, Catharina E. M.; Vasan, Ramachandran S.; Maier, Wolfgang; Peeters, Carel F. W.; Grabe, Hans Joergen; Ramirez, Alfredo; Seshadri, Sudha; Metspalu, Andres; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayse; Boomsma, Dorret I.; van der Flier, Wiesje M.; Amin, Najaf; van Duijn, Cornelia M.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, University College London
Date: 2018-06
Language: eng
Number of pages: 16
Belongs to series: Alzheimer's & Dementia
ISSN: 1552-5260
URI: http://hdl.handle.net/10138/236764
Abstract: Introduction: Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. Methods: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. Results: We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. Discussion: Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
Subject: Cognitive function
General cognitive ability
Alzheimer's disease
Dementia
Metabolites
Metabolomics
NMR
Lifestyle factors
GENOME-WIDE ASSOCIATION
ERASMUS RUCPHEN FAMILY
FATTY-ACID-COMPOSITION
LOTHIAN BIRTH COHORT
BLOOD-BRAIN-BARRIER
ALZHEIMERS-DISEASE
SERUM-CHOLESTEROL
UNITED-STATES
ROTTERDAM
HDL
3112 Neurosciences
3124 Neurology and psychiatry
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