A 74-year-old woman with mild Alzheimer disease joined a clinical trial of anti–amyloid-β therapy. Three weeks after receiving remternetug, a N3pH-Aβ monoclonal antibody, a scheduled brain MRI showed new periventricular and subcortical FLAIR hyperintensities (Figure, A) suggestive of mild amyloid-related imaging abnormalities (ARIA).1,2 Two weeks later, she was hospitalized for rapid cognitive and functional decline. Her admission examination was notable for severe disorientation, inattention, and global aphasia. Repeat MRI showed diffuse and confluent FLAIR hyperintensities consistent with progression to severe ARIA-edema/effusion (ARIA-E), but no hemosiderosis/microhemorrhages (ARIA-H) (Figure, B). She was treated with steroids and continued to have a gradual improvement in her cognition and language. A follow-up MRI 6 weeks later showed a marked reduction in FLAIR hyperintensities (Figure, C). In clinical trials, ARIA-E has often been observed to improve within 3–4 months.2 Early suspicion of ARIAs is essential for identifying and managing this adverse effect of anti–amyloid-β therapy.

(A) FLAIR hyperintensities in the periventricular and subcortical white matter. (B) At symptom onset 3 weeks later, MRI showed extensive confluent subcortical FLAIR hyperintensities, most prominently in the parieto-occipital lobes and right temporal lobe. No corresponding susceptibility, diffusion restriction, or postcontrast enhancement was observed. (C) Significant improvement after 6 weeks. FLAIR = fluid-attenuated inversion recovery.

S. Bonomi: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; Study concept or design; analysis or interpretation of data. A. Samara: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; Analysis or interpretation of data. N. Balestra: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; Study concept or design; analysis or interpretation of data. A. Padalia: drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; analysis or interpretation of data. T.L.S. Benzinger: drafting/revision of the manuscript for content, including medical writing for content; analysis or interpretation of data. P. Kang: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data.

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Submitted and externally peer reviewed. The handling editor was Resident & Fellow Section Editor Whitley Aamodt, MD, MPH.

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