TY - JOUR
T1 - Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer’s Disease Treated with Anti-Amyloid Beta Therapy
AU - Barakos, J
AU - Purcell, D
AU - Suhy, J
AU - Chalkias, S
AU - Burkett, P
AU - Marsica Grassi, C
AU - Castrillo-Viguera, C
AU - Rubino, I
AU - Vijverberg, E
N1 - Funding Information: Funding: The development of this manuscript was funded by Biogen Inc. Biogen Inc. funded medical writing support. Editorial support was provided by Robert Hodge, MSc, and Bethany Broughton, MSc, Helios Medical Communications, Cheshire, UK, which was funded by Biogen Inc. There are no other costs to declare. Publisher Copyright: © 2022, The Author(s).
PY - 2022/4
Y1 - 2022/4
N2 - Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer’s disease trials of anti-amyloid beta (Aβ) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/ sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aβ therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.
AB - Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer’s disease trials of anti-amyloid beta (Aβ) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/ sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aβ therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.
KW - Alzheimer Disease/diagnostic imaging
KW - Amyloid beta-Peptides/metabolism
KW - Amyloid/metabolism
KW - Antibodies, Monoclonal/therapeutic use
KW - Brain/metabolism
KW - Humans
KW - Magnetic Resonance Imaging
UR - http://www.scopus.com/inward/record.url?scp=85124318139&partnerID=8YFLogxK
U2 - https://doi.org/10.14283/jpad.2022.21
DO - https://doi.org/10.14283/jpad.2022.21
M3 - Review article
C2 - 35542992
SN - 2274-5807
VL - 9
SP - 211
EP - 220
JO - Journal of Prevention of Alzheimer's Disease
JF - Journal of Prevention of Alzheimer's Disease
IS - 2
ER -