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therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total\u00a0=\u00a05658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total\u00a0=\u00a06652), and the associations with dementia and Alzheimer's disease (N\u00a0=\u00a025,872) and lifestyle factors (N\u00a0=\u00a05168) were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We discovered and replicated 15 metabolites associated with cognition including subfractions of high\u2010density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high\u2010density lipoprotein cholesterol, low\u2010density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) genotypes. Six of the cognition\u2010associated metabolites were related to the risk of dementia and lifestyle factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jalz.2017.11.012","type":"journal-article","created":{"date-parts":[[2018,1,6]],"date-time":"2018-01-06T01:03:11Z","timestamp":1515200591000},"page":"707-722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":192,"title":["Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies"],"prefix":"10.1002","volume":"14","author":[{"given":"Sven J.","family":"van der Lee","sequence":"first","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory and Biobank Department of Clinical Chemistry VU University Medical Center Amsterdam Neuroscience Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Pool","sequence":"additional","affiliation":[{"name":"Department of Biological Psychology Vrije Universiteit Amsterdam Neuroscience Campus Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Shipley","sequence":"additional","affiliation":[{"name":"Research Department of Epidemiology and Public Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Teumer","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine University Medicine Greifswald Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Chouraki","sequence":"additional","affiliation":[{"name":"Lille University Inserm CHU Lille Institut Pasteur de Lille U1167 \u2010 RID\u2010AGE \u2010 Risk Factors and Molecular Determinants of Aging\u2010Related Diseases Labex Distalz Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Melo van Lent","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Center Rotterdam The Netherlands"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juho","family":"Tynkkynen","sequence":"additional","affiliation":[{"name":"University of Tampere Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Fischer","sequence":"additional","affiliation":[{"name":"The Institute of Genomics University of Tartu Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Hernesniemi","sequence":"additional","affiliation":[{"name":"University of Tampere Tampere Finland"},{"name":"Heart Center Tampere University Hospital Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toomas","family":"Haller","sequence":"additional","affiliation":[{"name":"The Institute of Genomics University of Tartu Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Singh\u2010Manoux","sequence":"additional","affiliation":[{"name":"Research Department of Epidemiology and Public Health University College London London UK"},{"name":"Inserm U1018 Centre for Research in Epidemiology and Population Health Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aswin","family":"Verhoeven","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonneke","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Department of Biological Psychology Vrije Universiteit Amsterdam Neuroscience Campus Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca A.","family":"de Leeuw","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory and Biobank Department of Clinical Chemistry VU University Medical Center Amsterdam Neuroscience Amsterdam The Netherlands"},{"name":"Alzheimer Center &amp; 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