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, Toomas Haller, Archana Singh-Manoux, Aswin Verhoeven, Gonneke Willemsen, Francisca 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. Eline Slagboom, Philip Scheltens, Qiong Yang, Robert E. Gertzen, Sarah Egert, Shuo Li, Thomas Hankemeier, Catharina E.M. van Beijsterveldt, Ramachandran S. Vasan, Wolfgang Maier, Carel F.W. Peeters, Hans Jörgen Grabe, Alfredo Ramirez, Sudha Seshadri, Andres Metspalu, Mika Kivimäki, Veikko Salomaa, Ayşe Demirkan, Dorret I. Boomsma, Wiesje M. van der Flier, Najaf Amin, Cornelia M. van Duijn

Research output: Contribution to JournalArticleAcademicpeer-review

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.

LanguageEnglish
Pages707-722
Number of pages16
JournalAlzheimers & Dementia
Volume14
Issue number6
Early online date6 Jan 2018
DOIs
StatePublished - Jun 2018

Fingerprint

Aptitude
Cognition
Dementia
Cohort Studies
Life Style
Ornithine
Docosahexaenoic Acids
Apolipoproteins E
HDL Lipoproteins
Glutamine
LDL Cholesterol
HDL Cholesterol
Glycoproteins
Alzheimer Disease
Genotype
Glucose

Keywords

  • Alzheimer's disease
  • Cognitive function
  • Dementia
  • General cognitive ability
  • Lifestyle factors
  • Metabolites
  • Metabolomics
  • NMR

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, 14(6), 707-722. 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 ; Haller, Toomas ; Singh-Manoux, Archana ; Verhoeven, Aswin ; Willemsen, Gonneke ; de Leeuw, Francisca 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. 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. ; Jörgen Grabe, Hans ; Ramirez, Alfredo ; Seshadri, Sudha ; Metspalu, Andres ; Kivimäki, Mika ; Salomaa, Veikko ; Demirkan, Ayşe ; Boomsma, Dorret I. ; 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. 2018 ; Vol. 14, No. 6. pp. 707-722
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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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van der Lee, SJ, Teunissen, CE, Pool, R, Shipley, MJ, Teumer, A, Chouraki, V, Melo van Lent, D, Tynkkynen, J, Fischer, K, Hernesniemi, J, Haller, T, 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, Vasan, RS, Maier, W, Peeters, CFW, Jörgen Grabe, H, Ramirez, A, Seshadri, S, Metspalu, A, Kivimäki, M, Salomaa, V, Demirkan, A, Boomsma, DI, 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, vol. 14, no. 6, pp. 707-722. 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; Haller, Toomas; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francisca 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. 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.; Jörgen Grabe, Hans; Ramirez, Alfredo; Seshadri, Sudha; Metspalu, Andres; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayşe; Boomsma, Dorret I.; van der Flier, Wiesje M.; Amin, Najaf; van Duijn, Cornelia M.

In: Alzheimers & Dementia, Vol. 14, No. 6, 06.2018, p. 707-722.

Research output: Contribution to JournalArticleAcademicpeer-review

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 - Haller,Toomas

AU - Singh-Manoux,Archana

AU - Verhoeven,Aswin

AU - Willemsen,Gonneke

AU - de Leeuw,Francisca 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. Eline

AU - Scheltens,Philip

AU - Yang,Qiong

AU - Gertzen,Robert E.

AU - Egert,Sarah

AU - Li,Shuo

AU - Hankemeier,Thomas

AU - van Beijsterveldt,Catharina E.M.

AU - Vasan,Ramachandran S.

AU - Maier,Wolfgang

AU - Peeters,Carel F.W.

AU - Jörgen Grabe,Hans

AU - Ramirez,Alfredo

AU - Seshadri,Sudha

AU - Metspalu,Andres

AU - Kivimäki,Mika

AU - Salomaa,Veikko

AU - Demirkan,Ayşe

AU - Boomsma,Dorret I.

AU - van der Flier,Wiesje M.

AU - Amin,Najaf

AU - van Duijn,Cornelia M.

PY - 2018/6

Y1 - 2018/6

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 - Alzheimer's disease

KW - Cognitive function

KW - Dementia

KW - General cognitive ability

KW - Lifestyle factors

KW - Metabolites

KW - Metabolomics

KW - NMR

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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 Jun;14(6):707-722. Available from, DOI: 10.1016/j.jalz.2017.11.012