Hithersay, R;
Baksh, RA;
Startin, CM;
Wijeratne, P;
Hamburg, S;
Carter, B;
LonDownS Consortium;
(2020)
Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome.
Alzheimer's & Dementia
10.1002/alz.12222.
(In press).
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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.
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