Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration

Objective: To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration. Methods: We evaluate an implementation of the recent National Institute for Aging–Alzheimer’s Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A1), neurodegeneration (N1), and their combination (A1N1) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost. Results: Enrichment based on an individual marker (A1 or N1) substantially improves all assessed trial characteristics. Combined enrichment (A1N1) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint. Conclusions: Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population. Neurology® 2016;87:1235–124