Changes in Brain Volume with Bapineuzumab in Mild to Moderate Alzheimer's Disease

J Alzheimers Dis. 2016;49(4):1123-34. doi: 10.3233/JAD-150448.


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.

Objectives: 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.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Apolipoprotein E4 / genetics
  • Brain / drug effects*
  • Brain / pathology*
  • Double-Blind Method
  • Female
  • Heterozygote
  • Humans
  • Least-Squares Analysis
  • Magnetic Resonance Imaging
  • Male
  • Nootropic Agents / therapeutic use*
  • Organ Size
  • Severity of Illness Index
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Apolipoprotein E4
  • Nootropic Agents
  • bapineuzumab