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Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be associated with cognitive decline, but population\u2010based evidence is lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Change in cognitive performance was assessed in participants of the Aberdeen Birth Cohort of 1936 using longitudinal Raven's progressive matrices (RPM) between 2000 and 2004. Multiple linear regression was used to estimate the association between ADMA concentrations in 2000 and change in cognitive performance after adjustment for potential confounders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 93 participants had complete information on cognitive performance between 2000 and 2004. Mean plasma ADMA concentrations were approximately 0.4 \u03bcmol\/L lower in those participants with stable or improved RPM scores over follow\u2010up compared with participants whose cognitive performance worsened. In confounder\u2010adjusted analysis, one SD (0.06\u2009\u03bcmol\/L) increase in ADMA at 63\u2009years of age was associated with an average reduction in RPM of 1.26 points (95% CI 0.14\u20102.26) after 4\u2009years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Raised plasma ADMA concentrations predicted worsening cognitive performance after approximately 4\u2009years in this cohort of adults in late\u2010middle age. These findings have implications for future research, including presymptomatic diagnosis or novel therapeutic targets for dementia and AD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/gps.5355","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T06:25:43Z","timestamp":1590474343000},"page":"1181-1188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Circulating asymmetric dimethylarginine and cognitive decline: A 4\u2010year follow\u2010up study of the 1936 Aberdeen Birth Cohort"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0567-8294","authenticated-orcid":false,"given":"Deborah E.","family":"Malden","sequence":"first","affiliation":[{"name":"Clinical Trial Service Unit &amp; Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health (NDPH) University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arduino A.","family":"Mangoni","sequence":"additional","affiliation":[{"name":"Discipline of Clinical Pharmacology, College of Medicine and Public Health Flinders University and Flinders Medical Centre  Adelaide Australia"},{"name":"Medizinische Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Woodman","sequence":"additional","affiliation":[{"name":"Flinders Centre for Epidemiology and Biostatistics, College of Medicine and Public Health Flinders University  Adelaide Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Thies","sequence":"additional","affiliation":[{"name":"Rowett institute University of Aberdeen  Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"McNeil","sequence":"additional","affiliation":[{"name":"Aberdeen Biomedical Imaging Centre University of Aberdeen  Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison D.","family":"Murray","sequence":"additional","affiliation":[{"name":"Aberdeen Biomedical Imaging Centre University of Aberdeen  Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy L.","family":"Soiza","sequence":"additional","affiliation":[{"name":"Ageing Clinical &amp; 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