TY - JOUR TI - Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration AV - restricted Y1 - 2016/09/20/ EP - 1241 KW - Aged KW - Alzheimer Disease KW - Amyloid beta-Peptides KW - Biomarkers KW - Brain KW - Clinical Trials as Topic KW - Cognitive Dysfunction KW - Cohort Studies KW - Female KW - Humans KW - Male KW - Mental Status Schedule KW - Nerve Degeneration KW - Positron-Emission Tomography N2 - 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 (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. ID - discovery10073276 IS - 12 N1 - This version is the version of record. For information on re-use, please refer to the publisher?s terms and conditions. SP - 1235 VL - 87 JF - Neurology A1 - Wolz, R A1 - Schwarz, AJ A1 - Gray, KR A1 - Yu, P A1 - Hill, DLG A1 - Alzheimer's Disease Neuroimaging Initiative UR - https://doi.org/10.1212/WNL.0000000000003126 SN - 1526-632X ER -