Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome
Volume
17
Pagination
595 - 604
Publisher
DOI
10.1002/alz.12222
Journal
Alzheimers Dement
Issue
Metadata
Show full item recordAbstract
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.
Authors
Hithersay, R; Baksh, RA; Startin, CM; Wijeratne, P; Hamburg, S; Carter, B; LonDownS Consortium; Strydom, ACollections
Language
Licence information
The following license files are associated with this item: