{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:32:33Z","timestamp":1791469953404,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cohort study. Event\u2010based and dose\u2010response E<jats:sub>max<\/jats:sub> models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline. Results informed sample size estimations for hypothetical RCTs of disease\u2010modifying treatments that reduced decline by 35% or 75%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventy\u2010five percent of participants progressed or remained stable in the AD staging model; effect sizes varied by age group and tests. Varied treatment effects could be detected with 50\u2010200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose\u2010response models could help tailor future RCTs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12222","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T23:06:45Z","timestamp":1606172805000},"page":"595-604","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome"],"prefix":"10.1002","volume":"17","author":[{"given":"Rosalyn","family":"Hithersay","sequence":"first","affiliation":[{"name":"Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"},{"name":"The LonDownS Consortium  London UK"},{"name":"Division of Psychiatry University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Asaad","family":"Baksh","sequence":"additional","affiliation":[{"name":"Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"},{"name":"The LonDownS Consortium  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla M.","family":"Startin","sequence":"additional","affiliation":[{"name":"Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"},{"name":"The LonDownS Consortium  London UK"},{"name":"Division of Psychiatry University College London  London UK"},{"name":"Department of Psychology University of York  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wijeratne","sequence":"additional","affiliation":[{"name":"Department of Computer Science University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hamburg","sequence":"additional","affiliation":[{"name":"Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry, Psychology &amp; 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