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

Sven J van der Lee, Charlotte E Teunissen, René Pool, Martin J Shipley, Alexander Teumer, Vincent Chouraki, Debora Melo van Lent, Juho Tynkkynen, Krista Fischer, Jussi Hernesniemi, Andres Metspalu, Archana Singh-Manoux, Aswin Verhoeven, Gonneke Willemsen, Francien A de Leeuw, Holger Wagner, Jenny van Dongen, Johannes Hertel, Kathrin Budde, Ko Willems van Dijk & 28 others Leonie Weinhold, M Arfan Ikram, Maik Pietzner, Markus Perola, Michael Wagner, Nele Friedrich, P E Slagboom, Philip Scheltens, Qiong Yang, Robert E Gertzen, Sarah Egert, Shuo Li, Thomas Hankemeier, Catharine E M van Beijsterveldt, Vasan Ramachandran, Wolfgang Maier, Carel F W Peeters, Hans Jörgen Grabe, Alfredo Ramirez, Sudha Seshadri, Toomas Haller, Mika Kivimäki, Veikko Salomaa, Ayşe Demirkan, Dorret Boomsma, Wiesje M van der Flier, Najaf Amin, Cornelia M van Duijn

Research output: Scientific - peer-reviewArticle

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.

Original languageEnglish
JournalAlzheimers & Dementia
DOIs
StateE-pub ahead of print - 6 Jan 2018

Cite this

van der Lee, S. J., Teunissen, C. E., Pool, R., Shipley, M. J., Teumer, A., Chouraki, V., ... van Duijn, C. M. (2018). Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies. Alzheimers & Dementia. DOI: 10.1016/j.jalz.2017.11.012

van der Lee, Sven J; Teunissen, Charlotte E; Pool, René; Shipley, Martin J; Teumer, Alexander; Chouraki, Vincent; Melo van Lent, Debora; Tynkkynen, Juho; Fischer, Krista; Hernesniemi, Jussi; Metspalu, Andres; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francien A; Wagner, Holger; van Dongen, Jenny; Hertel, Johannes; Budde, Kathrin; Willems van Dijk, Ko; Weinhold, Leonie; Ikram, M Arfan; Pietzner, Maik; Perola, Markus; Wagner, Michael; Friedrich, Nele; Slagboom, P E; Scheltens, Philip; Yang, Qiong; Gertzen, Robert E; Egert, Sarah; Li, Shuo; Hankemeier, Thomas; van Beijsterveldt, Catharine E M; Ramachandran, Vasan; Maier, Wolfgang; Peeters, Carel F W; Jörgen Grabe, Hans; Ramirez, Alfredo; Seshadri, Sudha; Haller, Toomas; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayşe; Boomsma, Dorret; van der Flier, Wiesje M; Amin, Najaf; van Duijn, Cornelia M / Circulating metabolites and general cognitive ability and dementia : Evidence from 11 cohort studies.

In: Alzheimers & Dementia, 06.01.2018.

Research output: Scientific - peer-reviewArticle

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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.",
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author = "{van der Lee}, {Sven J} and Teunissen, {Charlotte E} and René Pool and Shipley, {Martin J} and Alexander Teumer and Vincent Chouraki and {Melo van Lent}, Debora and Juho Tynkkynen and Krista Fischer and Jussi Hernesniemi and Andres Metspalu and Archana Singh-Manoux and Aswin Verhoeven and Gonneke Willemsen and {de Leeuw}, {Francien A} and Holger Wagner and {van Dongen}, Jenny and Johannes Hertel and Kathrin Budde and {Willems van Dijk}, Ko and Leonie Weinhold and Ikram, {M Arfan} and Maik Pietzner and Markus Perola and Michael Wagner and Nele Friedrich and Slagboom, {P E} and Philip Scheltens and Qiong Yang and Gertzen, {Robert E} and Sarah Egert and Shuo Li and Thomas Hankemeier and {van Beijsterveldt}, {Catharine E M} and Vasan Ramachandran and Wolfgang Maier and Peeters, {Carel F W} and {Jörgen Grabe}, Hans and Alfredo Ramirez and Sudha Seshadri and Toomas Haller and Mika Kivimäki and Veikko Salomaa and Ayşe Demirkan and Dorret Boomsma and {van der Flier}, {Wiesje M} and Najaf Amin and {van Duijn}, {Cornelia M}",
note = "Copyright © 2017. Published by Elsevier Inc.",
year = "2018",
month = "1",
doi = "10.1016/j.jalz.2017.11.012",
journal = "Alzheimers & Dementia",
issn = "1552-5260",
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van der Lee, SJ, Teunissen, CE, Pool, R, Shipley, MJ, Teumer, A, Chouraki, V, Melo van Lent, D, Tynkkynen, J, Fischer, K, Hernesniemi, J, Metspalu, A, Singh-Manoux, A, Verhoeven, A, Willemsen, G, de Leeuw, FA, Wagner, H, van Dongen, J, Hertel, J, Budde, K, Willems van Dijk, K, Weinhold, L, Ikram, MA, Pietzner, M, Perola, M, Wagner, M, Friedrich, N, Slagboom, PE, Scheltens, P, Yang, Q, Gertzen, RE, Egert, S, Li, S, Hankemeier, T, van Beijsterveldt, CEM, Ramachandran, V, Maier, W, Peeters, CFW, Jörgen Grabe, H, Ramirez, A, Seshadri, S, Haller, T, Kivimäki, M, Salomaa, V, Demirkan, A, Boomsma, D, van der Flier, WM, Amin, N & van Duijn, CM 2018, 'Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies' Alzheimers & Dementia. DOI: 10.1016/j.jalz.2017.11.012

Circulating metabolites and general cognitive ability and dementia : Evidence from 11 cohort studies. / van der Lee, Sven J; Teunissen, Charlotte E; Pool, René; Shipley, Martin J; Teumer, Alexander; Chouraki, Vincent; Melo van Lent, Debora; Tynkkynen, Juho; Fischer, Krista; Hernesniemi, Jussi; Metspalu, Andres; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francien A; Wagner, Holger; van Dongen, Jenny; Hertel, Johannes; Budde, Kathrin; Willems van Dijk, Ko; Weinhold, Leonie; Ikram, M Arfan; Pietzner, Maik; Perola, Markus; Wagner, Michael; Friedrich, Nele; Slagboom, P E; Scheltens, Philip; Yang, Qiong; Gertzen, Robert E; Egert, Sarah; Li, Shuo; Hankemeier, Thomas; van Beijsterveldt, Catharine E M; Ramachandran, Vasan; Maier, Wolfgang; Peeters, Carel F W; Jörgen Grabe, Hans; Ramirez, Alfredo; Seshadri, Sudha; Haller, Toomas; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayşe; Boomsma, Dorret; van der Flier, Wiesje M; Amin, Najaf; van Duijn, Cornelia M.

In: Alzheimers & Dementia, 06.01.2018.

Research output: Scientific - peer-reviewArticle

TY - JOUR

T1 - Circulating metabolites and general cognitive ability and dementia

T2 - Alzheimers & Dementia

AU - van der Lee,Sven J

AU - Teunissen,Charlotte E

AU - Pool,René

AU - Shipley,Martin J

AU - Teumer,Alexander

AU - Chouraki,Vincent

AU - Melo van Lent,Debora

AU - Tynkkynen,Juho

AU - Fischer,Krista

AU - Hernesniemi,Jussi

AU - Metspalu,Andres

AU - Singh-Manoux,Archana

AU - Verhoeven,Aswin

AU - Willemsen,Gonneke

AU - de Leeuw,Francien A

AU - Wagner,Holger

AU - van Dongen,Jenny

AU - Hertel,Johannes

AU - Budde,Kathrin

AU - Willems van Dijk,Ko

AU - Weinhold,Leonie

AU - Ikram,M Arfan

AU - Pietzner,Maik

AU - Perola,Markus

AU - Wagner,Michael

AU - Friedrich,Nele

AU - Slagboom,P E

AU - Scheltens,Philip

AU - Yang,Qiong

AU - Gertzen,Robert E

AU - Egert,Sarah

AU - Li,Shuo

AU - Hankemeier,Thomas

AU - van Beijsterveldt,Catharine E M

AU - Ramachandran,Vasan

AU - Maier,Wolfgang

AU - Peeters,Carel F W

AU - Jörgen Grabe,Hans

AU - Ramirez,Alfredo

AU - Seshadri,Sudha

AU - Haller,Toomas

AU - Kivimäki,Mika

AU - Salomaa,Veikko

AU - Demirkan,Ayşe

AU - Boomsma,Dorret

AU - van der Flier,Wiesje M

AU - Amin,Najaf

AU - van Duijn,Cornelia M

N1 - Copyright © 2017. Published by Elsevier Inc.

PY - 2018/1/6

Y1 - 2018/1/6

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.jalz.2017.11.012

DO - 10.1016/j.jalz.2017.11.012

M3 - Article

JO - Alzheimers & Dementia

JF - Alzheimers & Dementia

SN - 1552-5260

ER -

van der Lee SJ, Teunissen CE, Pool R, Shipley MJ, Teumer A, Chouraki V et al. Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies. Alzheimers & Dementia. 2018 Jan 6. Available from, DOI: 10.1016/j.jalz.2017.11.012