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Data\u2010driven methods can estimate long\u2010term trends from cross\u2010sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We applied an event\u2010based model to cognitive test data and informant\u2010rated questionnaire data from 283 adults with <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> (the largest study of cognitive functioning in <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> to date) to estimate the sequence of cognitive decline and individuals\u2019 disease stage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Decline in tests of memory, sustained attention\/motor coordination, and verbal fluency occurred early, demonstrating that <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> follows a similar pattern of change to other forms of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with <jats:italic>APOE<\/jats:italic> 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting that the model is valid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical\/prodromal stages of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content> whereas informant\u2010measures may be useful in later stages (i.e. during conversion into dementia, or postdiagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>. As clinical diagnoses are generally made late into <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> progression, early assessment is essential.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.571","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T04:10:48Z","timestamp":1526875848000},"page":"741-751","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Aging related cognitive changes associated with Alzheimer's disease in Down syndrome"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5391-3143","authenticated-orcid":false,"given":"Nicholas C.","family":"Firth","sequence":"first","affiliation":[{"name":"Centre for Medical Image Computing Department of Computer Science UCL London WC1E 6BT United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-9924","authenticated-orcid":false,"given":"Carla M.","family":"Startin","sequence":"additional","affiliation":[{"name":"Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry, Psychology &amp; 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