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We investigated trajectories of cognition and daily functioning in preclinical dementia, during 18\u00a0years of follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 856 dementia cases and 1712 controls, we repetitively assessed cognition and daily functioning with memory complaints, mini\u2010mental state examination (MMSE), instrumental activities of daily living (IADL), and basic activities of daily living (BADL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dementia cases first reported memory complaints 16\u00a0years before diagnosis, followed by decline in MMSE, IADL, and finally BADL. Vascular dementia related to earlier decline in daily functioning but later in cognition, compared with Alzheimer's disease. Higher education related to larger preclinical cognitive decline, whereas apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 carriers declined less in daily functioning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results emphasize the long hierarchical preclinical trajectory of functional decline in dementia. Furthermore, they show that various pathologic, environmental, and genetic factors may influence these trajectories of decline.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2015.08.001","type":"journal-article","created":{"date-parts":[[2015,9,9]],"date-time":"2015-09-09T01:50:50Z","timestamp":1441763450000},"page":"144-153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Trajectories of decline in cognition and daily functioning in preclinical dementia"],"prefix":"10.1002","volume":"12","author":[{"given":"Vincentius J.A.","family":"Verlinden","sequence":"first","affiliation":[{"name":"Department of Epidemiology Erasmus MC University Medical Centre Rotterdam  Rotterdam The Netherlands"},{"name":"Department of Radiology Erasmus MC University Medical Centre Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos N.","family":"van der Geest","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus MC University Medical Centre Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e F.A.G.","family":"de Bruijn","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus MC University Medical Centre Rotterdam  Rotterdam The Netherlands"},{"name":"Department of Neurology Erasmus MC University Medical Centre Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Hofman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus MC University Medical Centre Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Koudstaal","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus MC University Medical Centre Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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