Abstract
medRxiv [Preprint]. 2024 Nov 16:2024.11.12.24316919. doi: 10.1101/2024.11.12.24316919.
ABSTRACT
INTRODUCTION: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.
METHODS: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes.
RESULTS: Biomarkers measuring amyloid and tau pathology had required sample sizes below 200 participants per arm (examples CSF Aβ42/40: 22[95%CI 13,46], cortical PIB 32[20,57], CSF p-tau181 58[40,112]) for a four-year trial to have 80% power (5% statistical significance) to detect a 25% reduction in absolute levels of pathology, allowing 40% dropout. For cognitive, MRI, and FDG, it was more appropriate to detect a 50% reduction in rate of change. Sample sizes ranged from 75-250 (examples precuneus volume: 137[80,284], cortical FDG: 256[100,1208], CDR-SB: 161[102,291]).
DISCUSSION: Despite the rarity of ADAD, clinical trials with feasible sample sizes given the number of cases appear possible.
PMID:39606328 | PMC:PMC11601746 | DOI:10.1101/2024.11.12.24316919