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Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro\u2010atrial natriuretic peptide (MR\u2010proANP), C\u2010terminal endothelin\u20101 (CT\u2010proET\u20101) and midregional proadrenomedullin (MR\u2010proADM) with dementia and subtypes amongst community\u2010dwelling older adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A population\u2010based cohort of 5347 individuals (men, 70%; age, 69\u00a0\u00b1\u00a06\u00a0years) without prevalent dementia provided plasma for determination of MR\u2010proANP, CT\u2010proET\u20101 and MR\u2010proADM. Three\u2010hundred\u2010and\u2010seventy\u2010three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6\u00a0\u00b1\u00a01.3\u00a0years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher levels of MR\u2010proANP were significantly associated with increased risk of all\u2010cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07\u20131.36; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002, and 1.52; 1.21\u20131.89; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, respectively). Risk of all\u2010cause dementia increased across the quartiles of MR\u2010proANP (p for linear trend\u00a0= 0.004; Q4, 145\u20131681\u00a0pmol\u00a0L<jats:sup>\u22121<\/jats:sup> vs. Q1, 22\u201377 pmol\u00a0L<jats:sup>\u22121<\/jats:sup>: HR: 1.83; 95%CI: 1.23\u20132.71) and was most pronounced for vascular type (p for linear trend\u00a0=\u00a00.005: HR: 2.71; 95%CI: 1.14\u20136.46). Moreover, the two highest quartiles of CT\u2010proET\u20101 predicted vascular dementia with a cut\u2010off value at 68 pmol\u00a0L<jats:sup>\u22121<\/jats:sup> (Q3\u2013Q4, 68\u2013432\u00a0pmol\u00a0L<jats:sup>\u22121<\/jats:sup> vs. Q1\u2013Q2,4\u201368\u00a0pmol\u00a0L<jats:sup>\u22121<\/jats:sup>; HR: 1.94; 95%CI: 1.12\u20133.36). Elevated levels of MR\u2010proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Elevated plasma concentration of MR\u2010proANP is an independent predictor of all\u2010cause and vascular dementia. Pronounced increase in CT\u2010proET\u20101 indicates higher risk of vascular dementia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12621","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T17:11:24Z","timestamp":1492103484000},"page":"94-101","source":"Crossref","is-referenced-by-count":23,"title":["Biomarkers of microvascular endothelial dysfunction predict incident dementia: a population\u2010based prospective study"],"prefix":"10.1111","volume":"282","author":[{"given":"H.","family":"Holm","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6, Faculty of Medicine Lund University Malm\u00f6 Sweden"},{"name":"Department of Internal Medicine Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"N\u00e4gga","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit Department of Clinical Sciences, Malm\u00f6 Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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