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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, Ayse; Boomsma, Dorret I; van der Flier, Wiesje M; Amin, Najaf; van Duijn, Cornelia M.
Afiliación
  • van der Lee SJ; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Teunissen CE; Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands.
  • Pool R; Department of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
  • Shipley MJ; Research Department of Epidemiology and Public Health, University College London, London, UK.
  • Teumer A; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Chouraki V; Lille University, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Risk Factors and Molecular Determinants of Aging-Related Diseases, Labex Distalz, Lille, France.
  • Melo van Lent D; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Tynkkynen J; University of Tampere, Tampere, Finland.
  • Fischer K; The Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Hernesniemi J; University of Tampere, Tampere, Finland; Heart Center, Tampere University Hospital, Tampere, Finland.
  • Haller T; The Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Singh-Manoux A; Research Department of Epidemiology and Public Health, University College London, London, UK; Inserm U1018, Centre for Research in Epidemiology and Population Health, Villejuif, France.
  • Verhoeven A; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
  • Willemsen G; Department of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
  • de Leeuw FA; Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands; Alzheimer Center & Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
  • Wagner H; Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
  • van Dongen J; Department of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
  • Hertel J; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
  • Budde K; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Willems van Dijk K; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, T
  • Weinhold L; Department of Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany.
  • Ikram MA; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Pietzner M; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Perola M; National Institute of Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Wagner M; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
  • Friedrich N; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Slagboom PE; Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Scheltens P; Alzheimer Center & Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
  • Yang Q; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Gertzen RE; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Egert S; Department of Nutrition and Food Sciences, Nutritional Physiology, University of Bonn, Bonn, Germany.
  • Li S; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Hankemeier T; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Faculty of Science, Universiteit Leiden, Leiden, The Netherlands; Translational Epidemiology, Faculty Science, Leiden University, Leiden, The
  • van Beijsterveldt CEM; Department of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
  • Vasan RS; Department of Medicine, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA.
  • Maier W; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
  • Peeters CFW; Department of Epidemiology & Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands.
  • Jörgen Grabe H; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
  • Ramirez A; Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Psychiatry and Psychotherapy, Univ
  • Seshadri S; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.
  • Metspalu A; The Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Kivimäki M; Research Department of Epidemiology and Public Health, University College London, London, UK.
  • Salomaa V; National Institute of Health and Welfare, Helsinki, Finland.
  • Demirkan A; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
  • Boomsma DI; Department of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
  • van der Flier WM; Alzheimer Center & Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands; Department of Epidemiology & Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands.
  • Amin N; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • van Duijn CM; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Translational Epidemiology, Faculty Science, Leiden University, Leiden, The Netherlands. Electronic address: c.vanduijn@erasmusmc.nl.
Alzheimers Dement ; 14(6): 707-722, 2018 06.
Article en En | MEDLINE | ID: mdl-29316447
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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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Biomarcadores / Demencia / Disfunción Cognitiva Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2018 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Biomarcadores / Demencia / Disfunción Cognitiva Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2018 Tipo del documento: Article