Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome

Rosalyn Hithersay, R Asaad Baksh, Carla Startin, Peter A. Wijeratne, Sarah Hamburg, Ben Carter, André Strydom

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
JournalAlzheimers and Dementia
Publication statusPublished - 23 Nov 2020

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