title: Use of white matter reference regions for detection of change in florbetapir positron emission tomography from completed phase 3 solanezumab trials.
abstract: BACKGROUND
  We compared subject-specific white matter (SSWM) and whole cerebellum (CBL) reference regions for power to detect longitudinal change in amyloid positron emission tomography signal.
  
  
  METHODS
  Positive florbetapir positron emission tomography scans were analyzed from participants (66 placebo treated and 63 solanezumab treated) with mild dementia caused by Alzheimer's disease from the EXPEDITION and EXPEDITION2 studies. For comparison to CBL, a second normalization was performed on longitudinal data using an SSWM correction factor (SSWM normalization ratio [SSWMnr]). Analysis of covariance assessed baseline to 18-month change between treatment with solanezumab and placebo. Sample and effect size estimations provided magnitude of observed treatment changes.
  
  
  RESULTS
  Longitudinal percent change between placebo and solanezumab using CBL was not significant (P = .536) but was significant for SSWMnr (P = .042). Compared with CBL, SSWMnr technique increased the power to detect a treatment difference, more than tripling the effect size and reducing the sample size requirements by 85% to 90%.
  
  
  CONCLUSIONS
  Adjusting longitudinal standardized uptake value ratios with an SSWM reference region in these antiamyloid treatment trials increased mean change detection and decreased variance resulting in the substantial improvement in statistical power to detect change.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: afleisher@Lilly.com.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Fleisher
authors.affiliation: Avid Radiopharmaceuticals, Philadelphia, PA, USA.
authors.forename: Abhinay D
authors.initials: AD
authors.lastname: Joshi
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Sundell
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Kollack-Walker
authors.affiliation: Avid Radiopharmaceuticals, Philadelphia, PA, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.affiliation: inVentiv Health, Inc., Burlington, MA, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Chen
authors.affiliation: Avid Radiopharmaceuticals, Philadelphia, PA, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Devous
authors.affiliation: Molecular NeuroImaging, New Haven, CT, USA.
authors.forename: John
authors.initials: J
authors.lastname: Seibyl
authors.affiliation: Molecular NeuroImaging, New Haven, CT, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Marek
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Siemers
authors.affiliation: Avid Radiopharmaceuticals, Philadelphia, PA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D000814:Aniline Compounds / Q000378:metabolism*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D004311:Double-Blind Method; D005026:Ethylene Glycols / Q000378:metabolism*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D066127:White Matter / Q000000981:diagnostic imaging* / Q000187:drug effects
chemical_list: D000814:Aniline Compounds; D061067:Antibodies, Monoclonal, Humanized; D005026:Ethylene Glycols; D007155:Immunologic Factors; C550616:solanezumab; C545186:florbetapir
keywords: Alzheimer's disease; Disease course; Florbetapir; Growth mixture model; Reference region; Serial PET imaging; Solanezumab; Trajectory