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<jats:title>Introduction<\/jats:title>\n                    <jats:p>Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Over 246,698 person\u2010years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched\u2010chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)\u2010specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched\u2010chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jalz.2018.01.003","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T20:25:21Z","timestamp":1520281521000},"page":"723-733","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":272,"title":["Association of branched\u2010chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts"],"prefix":"10.1002","volume":"14","author":[{"given":"Juho","family":"Tynkkynen","sequence":"first","affiliation":[{"name":"Department of Cardiology Tays Heart Hospital Tampere University Hospital and Faculty of Medicine and Life Sciences University of Tampere Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Chouraki","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University School of Medicine Boston MA USA"},{"name":"The Framingham Heart Study Framingham MA USA"},{"name":"Lille University Inserm Lille University Hospital 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":"Sven J.","family":"van der Lee","sequence":"additional","affiliation":[{"name":"Department of Epidemiology ErasmusMC Rotterdam The 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