title: Changes in Brain Volume with Bapineuzumab in Mild to Moderate Alzheimer's Disease.
abstract: BACKGROUND
  Bapineuzumab, an anti-amyloid-β monoclonal antibody, was evaluated in two placebo-controlled trials in APOE*ɛ4 carriers and noncarriers, respectively, with Alzheimer's disease.
  
  
  OBJECTIVE
  A volumetric magnetic resonance imaging substudy was performed to determine if bapineuzumab altered brain volume rate of change.
  
  
  METHODS
  Bapineuzumab dosages included 0.5 mg/kg in carriers and 0.5 or 1.0 mg/kg in noncarriers, every 13 weeks for 78 weeks. Volumetric outcomes included annualized brain, ventricular, and mean hippocampal boundary shift integrals (BBSI; VBSI; HBSI) up to Week 71. Treatment differences were estimated using mixed models for repeated measures.
  
  
  RESULTS
  For BBSI and HBSI, there were no significant treatment-related differences within either study, but, compared to pooled carriers and noncarriers receiving placebo, noncarriers receiving1.0 mg/kg bapineuzumab had greater increases in these measures. Bapineuzumab-treated patients showed significantly greater VBSI rates compared with placebo for 0.5 mg/kg in carriers and 1.0 mg/kg (but not 0.5 mg/kg) in noncarriers.
  
  
  CONCLUSIONS
  Bapineuzumab produced an increase in ventricular volume compared with placebo. Etiology for this increase is unclear but may be related to amyloid-β clearance or its consequences.
authors.affiliation: Janssen Research and Development, Titusville, NJ, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Novak
authors.affiliation: Dementia Research Centre, University College London Institute of Neurology, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Fox
authors.affiliation: Dementia Research Centre, University College London Institute of Neurology, London, UK.
authors.forename: Shona
authors.initials: S
authors.lastname: Clegg
authors.affiliation: Dementia Research Centre, University College London Institute of Neurology, London, UK.
authors.forename: Casper
authors.initials: C
authors.lastname: Nielsen
authors.affiliation: Janssen Research and Development, Titusville, NJ, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Einstein
authors.affiliation: Jazz Pharmaceuticals, Palo Alto, CA, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Medivation, Inc., San Francisco, CA, USA.
authors.forename: Iulia Cristina
authors.initials: IC
authors.lastname: Tudor
authors.affiliation: Janssen Alzheimer Immunotherapy, South San Francisco, CA, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Gregg
authors.affiliation: Janssen Research and Development, San Diego, CA, USA.
authors.forename: Jianing
authors.initials: J
authors.lastname: Di
authors.affiliation: BioMarin, Novato, CA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Collins
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Wyman
authors.affiliation: Janssen Alzheimer Immunotherapy, South San Francisco, CA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Yuen
authors.affiliation: Global R&D Partners, LLC, San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Grundman
authors.affiliation: Janssen Research and Development, Fremont, CA, USA.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Brashear
authors.affiliation: Janssen Research and Development, San Diego, CA, USA.
authors.forename: Enchi
authors.initials: E
authors.lastname: Liu
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006579:Heterozygote; D006801:Humans; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D018697:Nootropic Agents / Q000627:therapeutic use*; D009929:Organ Size; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D053327:Apolipoprotein E4; D018697:Nootropic Agents; C545458:bapineuzumab
keywords: Alzheimer’s disease; bapineuzumab; brain boundary shift integral; brain volume; hippocampal boundary shift integral; magnetic resonance imaging; randomized controlled trial; ventricular boundary shift integral; ventricular volume