Article Text

Research paper
Amyloid-related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer's disease treated with bapineuzumab: a historical, prospective secondary analysis
  1. H Michael Arrighi1,
  2. Jerome Barakos2,3,
  3. Frederik Barkhof4,5,
  4. Donatella Tampieri6,
  5. Clifford Jack Jr7,
  6. Denis Melançon7,
  7. Kristen Morris8,9,
  8. Nzeera Ketter1,
  9. Enchi Liu1,
  10. H Robert Brashear1
  1. 1Janssen Research & Development, South San Francisco, California, USA
  2. 2California Pacific Medical Center, San Francisco, California, USA
  3. 3Synarc, Newark, California, USA
  4. 4Department of Radiology, Image Analysis Centre, VU University Medical Center, Amsterdam, The Netherlands
  5. 5Department of Diagnostic Radiology, VU University Medical Center, Amsterdam, The Netherlands
  6. 6NeuroRx Research, Montreal, Canada
  7. 7Mayo Clinic, Rochester, Minnesota, USA
  8. 8Janssen Alzheimer Immunotherapy R&D, South San Francisco, California, USA
  9. 9BioMarin, San Rafael, California, USA
  1. Correspondence to Dr H Michael Arrighi, Janssen Pharmaceuticals Research & Development, 40 King Street, Mill Valley, South San Francisco, CA 94941, USA; marrighi{at}


Background Amyloid-related imaging abnormalities due to haemosiderin deposition (ARIA-H) occur in patients with mild to moderate dementia due to Alzheimer's disease (AD) and have been reported with increased incidence in clinical trials of amyloid-lowering therapies under development for AD.

Objective Our objective was to explore the relationship between the incidences of ARIA-H during treatment with placebo and different doses of bapineuzumab, a humanised monoclonal antibody directed against amyloid β.

Methods Two neuroradiologists independently reviewed 2572 GRE/T2* MRI sequences from 262 participants in two phase two clinical trials of bapineuzumab and an open-label extension study. Readers were blinded to the participant's therapy, APOE ε4 genotype and medical history.

Results Several risk factors for small ARIA-H <10 mm (microhaemorrhages) were identified: APOE ε4, bapineuzumab treatment, pre-existing small ARIA-H and use of antithrombotics. The HR (95%CI) for incident ARIA-H <10 mm associated with the number of APOE ε4 alleles was 11.9 (3.3 to 42.5) for 2 versus no alleles and 3.5 (1.0 to 12.0) for 1 versus no allele. The HR for bapineuzumab therapy was 3.5 (1.0 to 12.0); for the presence of baseline ARIA-H <10 mm, it was 3.5 (1.6 to 7.8), and for the use of antithrombotic agents it was 2.2 (1.0 to 4.8). The incidence rate for ARIA-H <10 mm was elevated only in the initial 6 months of active treatment and declined after this interval to a rate similar to that observed in the group treated with placebo.

Conclusions ARIA-H represents a spectrum of MRI findings due to haemosiderin deposition that appears to be related to impaired vascular integrity. The increased risk for ARIA-H associated with APOE ε4 allele frequency, pre-existing ARIA-H, treatment with bapineuzumab and use of antithrombotic agents provides additional support for this hypothesis of loss of integrity of cerebral vessels due to amyloid burden.

Trial registration NCT00112073 and NCT00606476.

  • MRI

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