Anti-amyloid monoclonal antibodies such as donanemab can cause amyloid-related imaging abnormalities: edema or effusion (ARIA-E) and hemorrhagic changes (ARIA-H). Donanemab protocols include baseline and early safety MRIs, along with symptom-triggered scans. However, the timing and predictors of severe early ARIA remain uncertain. Baseline microbleed burden, their distribution, and APOE ε4 carrier status may influence susceptibility and warrant closer monitoring.

A 73-year-old woman with Alzheimer’s disease began donanemab therapy after a baseline MRI showing three lobar microbleeds without cortical superficial siderosis, meeting the eligibility limit of ≤4 microbleeds. A post-first-infusion MRI showed no new abnormalities. Ten days before hospitalization on 08/22/2025, she developed progressive confusion, becoming nonverbal and nonambulatory. MRI on 08/24/2025 revealed multifocal vasogenic edema in bilateral frontal, parietal, and left temporal regions, consistent with severe ARIA-E. Susceptibility sequences demonstrated numerous new lobar microhemorrhages and extensive cortical superficial siderosis, consistent with severe ARIA-H, without enhancement or diffusion restriction. Donanemab was discontinued, and she received high-dose intravenous corticosteroids followed by tapering, leading to gradual clinical improvement and discharge to rehabilitation.

This case underscores that severe ARIA can occur early after donanemab initiation, even in patients meeting current MRI eligibility criteria. Prompt MRI evaluation is essential for any new neurological symptoms. Future studies should refine safety monitoring, identify early predictors such as microbleed burden and APOE ε4 status, and optimize MRI scheduling to improve early detection and patient outcomes.