Wolz, RobinSchwarz, Adam J.Gray, Katherine R.Yu, PengHill, Derek L.G.2018-03-122018-03-122016-09-20Wolz, R., Schwarz, A. J., Gray, K. R., Yu, P., & Hill, D. L. G. (2016). Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration. Neurology, 87(12), 1235–1241. https://doi.org/10.1212/WNL.00000000000031260028-3878https://hdl.handle.net/1805/15429Objective: 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 (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost. Results: Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) 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.en-USPublisher PolicyMCIclinical trialsAlzheimer diseaseneurodegenerationArticle