• H Michael Arrighi, Jerome Barakos, Frederik Barkhof, Donatella Tampieri, Clifford Jack, Denis Melançon, Kristen Morris, Nzeera Ketter, Enchi Liu, and H Robert Brashear.
• Janssen Research & Development, South San Francisco, California, USA.
• J. Neurol. Neurosurg. Psychiatr. 2016 Jan 1;87(1):106-12.

BackgroundAmyloid-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.ObjectiveOur 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.MethodsTwo 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.ResultsSeveral 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.ConclusionsARIA-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 RegistrationNCT00112073 and NCT00606476.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

46 keywords...

hide…