dc.contributor.author | Hithersay, R | |
dc.contributor.author | Baksh, RA | |
dc.contributor.author | Startin, CM | |
dc.contributor.author | Wijeratne, P | |
dc.contributor.author | Hamburg, S | |
dc.contributor.author | Carter, B | |
dc.contributor.author | LonDownS Consortium | |
dc.contributor.author | Strydom, A | |
dc.date.accessioned | 2024-01-03T09:55:06Z | |
dc.date.available | 2020-10-06 | |
dc.date.available | 2024-01-03T09:55:06Z | |
dc.date.issued | 2020-11-23 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/93295 | |
dc.description.abstract | INTRODUCTION: 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). METHODS: Cohort study. Event-based and dose-response Emax 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-modifying treatments that reduced decline by 35% or 75%. RESULTS: Seventy-five 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 50-200 people per arm when using sensitive cognitive outcome measures and targeting recruitment to ages 36 to 45 years. DISCUSSION: Efficient RCTs of AD preventative treatments can be conducted in the DS population using sensitive outcome measures to monitor early decline. Dose-response models could help tailor future RCTs. | en_US |
dc.format.extent | 595 - 604 | |
dc.language | eng | |
dc.publisher | Wiley Open Access | en_US |
dc.relation.ispartof | Alzheimers Dement | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | Alzheimer's disease | en_US |
dc.subject | Down syndrome | en_US |
dc.subject | clinical trial design | en_US |
dc.subject | cognitive decline | en_US |
dc.subject | Adult | en_US |
dc.subject | Age Factors | en_US |
dc.subject | Alzheimer Disease | en_US |
dc.subject | Cohort Studies | en_US |
dc.subject | Down Syndrome | en_US |
dc.subject | England | en_US |
dc.subject | Female | en_US |
dc.subject | Humans | en_US |
dc.subject | Longitudinal Studies | en_US |
dc.subject | Male | en_US |
dc.subject | Middle Aged | en_US |
dc.subject | Outcome Assessment, Health Care | en_US |
dc.subject | Prodromal Symptoms | en_US |
dc.subject | Research Design | en_US |
dc.subject | Sample Size | en_US |
dc.title | Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1002/alz.12222 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/33226718 | en_US |
pubs.issue | 4 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 17 | en_US |
dcterms.dateAccepted | 2020-10-06 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |