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While typically asymptomatic, a subset of patients develops severe clinical symptoms and radiological findings requiring intensive management. Data on their presentation, treatment, and outcomes remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We report two cases and analyze the clinical features of all published cases of severe symptomatic ARIA, with a focus on associated risk factors, therapeutic approaches, and patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We report two cases of severe symptomatic ARIA in patients treated with gantenerumab. A systematic review was conducted following PRISMA guidelines using MEDLINE, Web of Science, and manual reference screening. We included case reports and series providing individual-level data on symptomatic ARIA episodes classified as severe by clinical criteria. Demographic, genetic, clinical, radiological, therapeutic, and outcome data were extracted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-six cases were included (2 new and 34 from 21 publications). Fifteen cases were associated with lecanemab, 10 with gantenerumab, 6 with donanemab, and 5 with other antibodies.\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 was present in 62.5%, including 10 \u03b54\/\u03b54 homozygotes. Baseline MRI showed hemorrhagic markers in 10 cases, including superficial siderosis in 2 of the 5 patients with isolated macrohemorrhages. Most episodes occurred within 6 months of treatment. Symptoms included altered consciousness (75%), focal deficits (66.7%), seizures (38.9%), and headache (36.1%). ARIA-E resolved in all non-fatal cases. Corticosteroids were used in 72%. Among the patients whose outcome data were available, 15 patients recovered completely, 10 had persistent deficits, and 10 died.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Severe symptomatic ARIA is a rare but serious adverse effect of anti-amyloid therapy. Standardized diagnostic and therapeutic guidelines are needed to minimize ARIA-related morbidity and mortality.<\/jats:p>\n                    <jats:p>PROSPERO registration no. CRD420251055067<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251404505","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T14:59:21Z","timestamp":1765551561000},"page":"1099-1116","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Severe symptomatic amyloid-related imaging abnormalities in Alzheimer's disease: Two case reports and systematic review of reported cases"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6834-7620","authenticated-orcid":false,"given":"Alberto","family":"Villarejo Galende","sequence":"first","affiliation":[{"name":"Department of Neurology, Hospital Universitario \u201c12 de Octubre\u201d, Madrid, Spain"},{"name":"Group of Neurodegenerative Diseases, Imas12, Madrid, Spain"},{"name":"Department of Medicine, Faculty of Medicine, Complutense University, Madrid, 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