title: Sample Size Estimation for Alzheimer's Disease Trials from Japanese ADNI Serial Magnetic Resonance Imaging.
abstract: Little is known about the sample sizes required for clinical trials of Alzheimer's disease (AD)-modifying treatments using atrophy measures from serial brain magnetic resonance imaging (MRI) in the Japanese population.
  
  
  
  The primary objective of the present study was to estimate how large a sample size would be needed for future clinical trials for AD-modifying treatments in Japan using atrophy measures of the brain as a surrogate biomarker.
  
  
  
  Sample sizes were estimated from the rates of change of the whole brain and hippocampus by the k-means normalized boundary shift integral (KN-BSI) and cognitive measures using the data of 537 Japanese Alzheimer's Neuroimaging Initiative (J-ADNI) participants with a linear mixed-effects model. We also examined the potential use of ApoE status as a trial enrichment strategy.
  
  
  
  The hippocampal atrophy rate required smaller sample sizes than cognitive measures of AD and mild cognitive impairment (MCI). Inclusion of ApoE status reduced sample sizes for AD and MCI patients in the atrophy measures.
  
  
  
  These results show the potential use of longitudinal hippocampal atrophy measurement using automated image analysis as a progression biomarker and ApoE status as a trial enrichment strategy in a clinical trial of AD-modifying treatment in Japanese people.
authors.affiliation: Integrative Brain Imaging Center (IBIC), National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.|Department of Diagnostic Radiology, Kojinkai Josai Clinic, Maebashi, Gunma, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Fujishima
authors.affiliation: Center for Comprehensive Community Medicine, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Integrative Brain Imaging Center (IBIC), National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Maikusa
authors.affiliation: Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kuwano
authors.affiliation: Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.affiliation: Integrative Brain Imaging Center (IBIC), National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy / Q000000981:diagnostic imaging / Q000209:etiology; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007564:Japan / Q000453:epidemiology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D018401:Sample Size
chemical_list: D001057:Apolipoproteins E
keywords: Alzheimer’s disease; J-ADNI; apolipoprotein E ɛ4; boundary shift integral; brain atrophy; sample size