Amyloid-related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer's disease treated with bapineuzumab: a historical, prospective secondary analysis.
J Neurol Neurosurg Psychiatry
; 87(1): 106-12, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-25669746
ABSTRACT
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 ß.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 <10â 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 <10â 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 <10â 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 <10â mm was elevated only in the initial 6â 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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
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Nootrópicos
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Placa Amiloide
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Enfermedad de Alzheimer
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Anticuerpos Monoclonales Humanizados
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Hemosiderina
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurol Neurosurg Psychiatry
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos