Amyloid-related imaging abnormalities (ARIA) are changes identified in patients who have been treated for Alzheimer disease (AD) with amyloid-modifying agents and may also occur spontaneously in patients with AD. The condition was originally described in 2010 in clinical trials of monoclonal antibodies targeting amyloid beta (Aβ). ARIA is thought to occur due to the binding of monoclonal antibodies to Aβ plaques. The resulting amyloid clearance compromises vessel wall integrity and heightens vascular permeability. Amyloid-modifying agents include aducanumab (discontinued by the manufacturer), lecanemab, and donanemab.

Cases tend to occur early in treatment with amyloid-modifying agents; most cases are reported within the first 8 doses. While ARIA is most often asymptomatic, it can be life-threatening, and fatalities have occurred.

Risk increases in patients with a medical history of brain hemorrhage or superficial siderosis, APOE-e4 allele carriership, high-dose amyloid-modifying therapy, or concomitant antithrombotic medication use.

The spectrum of ARIA phenomena includes ARIA with edema and/or effusion (ARIA-E) and ARIA with hemosiderin deposition including hemorrhage or superficial siderosis (ARIA-H). Both ARIA-E and ARIA-H can be seen in an individual, and ARIA-H is generally associated with ARIA-E. Patients are usually asymptomatic and diagnosed only by MRI.

When reported, symptoms more often occur in ARIA-E and include headache, confusion, focal neurologic deficits, vision problems, and gait disturbance. More serious manifestations include seizures and status epilepticus. ARIA-E is described as parenchymal edema with or without sulcal effusion. In ARIA-E, proteinaceous fluid may leak or effuse from meningeal vessels. ARIA-E occurs weeks to months after initiation with amyloid-modifying agents. The condition appears to be transient, and the imaging abnormalities are reported to resolve in the majority of cases. ARIA-E has been reported with an approximate incidence between 8% and 27%.

ARIA-H is described as leakage of heme products resulting in microhemorrhages, and more rarely resulting in superficial siderosis. The hemosiderin deposits are thought to be due to vessel wall leakage into the parenchyma and/or sulcal space. ARIA-H has been reported with an approximate incidence between 4.6% and 30.5%. ARIA-H is not reversible. A high number of microhemorrhage lesions or presence of superficial siderosis may require cessation of amyloid-modifying therapy. Fatal events of intracerebral hemorrhage have occurred in ARIA-H.