van der Lee, Sven J., Teunissen, Charlotte E., Pool, Rene, Shipley, Martin J., Teumer, Alexander ORCID: 0000-0002-8309-094X, Chouraki, Vincent, van Lent, Debora Melo, Tynkkynen, Juho ORCID: 0000-0001-9882-9180, Fischer, Krista, Hernesniemi, Jussi, Haller, Toomas ORCID: 0000-0002-5069-6523, Singh-Manoux, Archana ORCID: 0000-0002-1244-5037, Verhoeven, Aswin, Willemsen, Gonneke ORCID: 0000-0003-3755-0236, de Leeuw, Francisca A., Wagner, Holger, van Dongen, Jenny ORCID: 0000-0003-2063-8741, Hertel, Johannes, Budde, Kathrin, van Dijk, Ko Willems ORCID: 0000-0002-2172-7394, Weinhold, Leonie, Ikram, M. Arfan, Pietzner, Maik, Perola, Markus, Wagner, Michael ORCID: 0000-0003-2589-6440, Friedrich, Nele, Slagboom, P. Eline, Scheltens, Philip ORCID: 0000-0002-1046-6408, Yang, Qiong, Gertzen, Robert E., Egert, Sarah, Li, Shuo, Hankemeier, Thomas ORCID: 0000-0001-7871-2073, van Beijsterveldt, Catharina E. M., Vasan, Ramachandran S., Maier, Wolfgang, Peeters, Carel F. W., Grabe, Hans Joergen, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Seshadri, Sudha ORCID: 0000-0001-6135-2622, Metspalu, Andres, Kivimaki, Mika ORCID: 0000-0002-4699-5627, Salomaa, Veikko, Demirkan, Ayse ORCID: 0000-0002-7546-0867, Boomsma, Dorret I., van der Flier, Wiesje M., Amin, Najaf and van Duijn, Cornelia M. (2018). Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies. Alzheimers. Dement., 14 (6). S. 707 - 723. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1552-5279

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
van der Lee, Sven J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teunissen, Charlotte E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pool, ReneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shipley, Martin J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teumer, AlexanderUNSPECIFIEDorcid.org/0000-0002-8309-094XUNSPECIFIED
Chouraki, VincentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Lent, Debora MeloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tynkkynen, JuhoUNSPECIFIEDorcid.org/0000-0001-9882-9180UNSPECIFIED
Fischer, KristaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernesniemi, JussiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haller, ToomasUNSPECIFIEDorcid.org/0000-0002-5069-6523UNSPECIFIED
Singh-Manoux, ArchanaUNSPECIFIEDorcid.org/0000-0002-1244-5037UNSPECIFIED
Verhoeven, AswinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willemsen, GonnekeUNSPECIFIEDorcid.org/0000-0003-3755-0236UNSPECIFIED
de Leeuw, Francisca A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Dongen, JennyUNSPECIFIEDorcid.org/0000-0003-2063-8741UNSPECIFIED
Hertel, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Budde, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Dijk, Ko WillemsUNSPECIFIEDorcid.org/0000-0002-2172-7394UNSPECIFIED
Weinhold, LeonieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ikram, M. ArfanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietzner, MaikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perola, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Friedrich, NeleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Slagboom, P. ElineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheltens, PhilipUNSPECIFIEDorcid.org/0000-0002-1046-6408UNSPECIFIED
Yang, QiongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gertzen, Robert E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Egert, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, ShuoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hankemeier, ThomasUNSPECIFIEDorcid.org/0000-0001-7871-2073UNSPECIFIED
van Beijsterveldt, Catharina E. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vasan, Ramachandran S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peeters, Carel F. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grabe, Hans JoergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
Seshadri, SudhaUNSPECIFIEDorcid.org/0000-0001-6135-2622UNSPECIFIED
Metspalu, AndresUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kivimaki, MikaUNSPECIFIEDorcid.org/0000-0002-4699-5627UNSPECIFIED
Salomaa, VeikkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demirkan, AyseUNSPECIFIEDorcid.org/0000-0002-7546-0867UNSPECIFIED
Boomsma, Dorret I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Flier, Wiesje M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amin, NajafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Duijn, Cornelia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-183193
DOI: 10.1016/j.jalz.2017.11.012
Journal or Publication Title: Alzheimers. Dement.
Volume: 14
Number: 6
Page Range: S. 707 - 723
Date: 2018
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1552-5279
Language: English
Faculty: Faculty of Management, Economy and Social Sciences
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; ERASMUS RUCPHEN FAMILY; FATTY-ACID-COMPOSITION; LOTHIAN BIRTH COHORT; BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; SERUM-CHOLESTEROL; UNITED-STATES; ROTTERDAM; HDLMultiple languages
Clinical NeurologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18319

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