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

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 E-max 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.

Automated summary

The study found that 75% of participants with Down syndrome progressed or remained stable in the Alzheimer's disease staging model; effect sizes varied by age group and tests. Different 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.