Amyloid-Related Imaging Abnormalities: An Update

Abstract

Amyloid-related imaging abnormalities (ARIA) is a term introduced in 2010 to encompass a spectrum of MRI findings observed in patients receiving investigational anti-amyloid beta (Aβ) immunotherapies for Alzheimer disease (AD). The entity can be broadly categorized into ARIA characterized by edema and effusion (ARIA-E) and ARIA characterized by microhemorrhages and superficial siderosis (ARIA-H). ARIA typically occurs early in the treatment course and has a higher incidence in patients who are apolipoprotein E ε4 allele carriers. ARIA-E has an additional dose dependence, with higher incidence in patients receiving higher doses of anti-Aβ immuno-therapies. ARIA is often asymptomatic and self-resolving. The recognition of ARIA has implications for patient selection and monitoring for Aβ immunotherapies, and its development can potentially lead to a pause or discontinuation of therapy. The FDA's first approval of an Aβ-targeting monoclonal antibody for AD treatment in 2021 will lead to such therapy's expanded use beyond the clinical trial setting and to radiologists more commonly encountering ARIA in clinical practice. This review explores the theorized pathophysiologic mechanisms for ARIA, describes the MRI findings and grading schemes for ARIA-E and AREA-H, and summarizes relevant Aβ immunotherapies. Through such knowledge, radiologists can optimally impact the management of patients receiving targeted AD therapies.

Keywords: ARIA; ARIA-E; ARIA-H; Alzheimer disease; MRI; amyloid beta; amyloid-related imaging abnormalities; edema; hemosiderin.