title: Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration.
abstract: 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.
authors: From IXICO Plc (R.W., K.R.G., D.L.G.H.), London, UK; Department of Computing (R.W., K.R.G.,), Imperial College London, UK; Eli Lilly and Company (A.J.S., P.Y.), Indianapolis, IN; Department of Psychology and Brain Sciences (A.J.S.), Indiana University, Bloomington; and Department of Radiology and Imaging Sciences (A.J.S.), Indiana University School of Medicine, Indianapolis. rwolz@ixico.com.
authors: Robin
authors: R
authors: Wolz
authors: From IXICO Plc (R.W., K.R.G., D.L.G.H.), London, UK; Department of Computing (R.W., K.R.G.,), Imperial College London, UK; Eli Lilly and Company (A.J.S., P.Y.), Indianapolis, IN; Department of Psychology and Brain Sciences (A.J.S.), Indiana University, Bloomington; and Department of Radiology and Imaging Sciences (A.J.S.), Indiana University School of Medicine, Indianapolis.
authors: Adam J
authors: AJ
authors: Schwarz
authors: From IXICO Plc (R.W., K.R.G., D.L.G.H.), London, UK; Department of Computing (R.W., K.R.G.,), Imperial College London, UK; Eli Lilly and Company (A.J.S., P.Y.), Indianapolis, IN; Department of Psychology and Brain Sciences (A.J.S.), Indiana University, Bloomington; and Department of Radiology and Imaging Sciences (A.J.S.), Indiana University School of Medicine, Indianapolis.
authors: Katherine R
authors: KR
authors: Gray
authors: From IXICO Plc (R.W., K.R.G., D.L.G.H.), London, UK; Department of Computing (R.W., K.R.G.,), Imperial College London, UK; Eli Lilly and Company (A.J.S., P.Y.), Indianapolis, IN; Department of Psychology and Brain Sciences (A.J.S.), Indiana University, Bloomington; and Department of Radiology and Imaging Sciences (A.J.S.), Indiana University School of Medicine, Indianapolis.
authors: Peng
authors: P
authors: Yu
authors: From IXICO Plc (R.W., K.R.G., D.L.G.H.), London, UK; Department of Computing (R.W., K.R.G.,), Imperial College London, UK; Eli Lilly and Company (A.J.S., P.Y.), Indianapolis, IN; Department of Psychology and Brain Sciences (A.J.S.), Indiana University, Bloomington; and Department of Radiology and Imaging Sciences (A.J.S.), Indiana University School of Medicine, Indianapolis.
authors: Derek L G
authors: DL
authors: Hill
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000191:economics / Q000379:methods; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009410:Nerve Degeneration / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers