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Severe symptomatic amyloid-related imaging abnormalities in Alzheimer's disease: Two case reports and systematic review of reported cases
Villarejo Galende A, González-Sánchez M, Hilario A, Llamas-Velasco S, Morenas-Rodríguez E, Muñoz-García MI, Ramos-González A, Pérez-Martínez DA et al.. Journal of Alzheimer's disease : JAD, 2025-12-12
Topic: Amyloid, tau and blood-test diagnosis
BackgroundAmyloid-related imaging abnormalities (ARIA) are a recognized complication of anti-amyloid monoclonal antibodies for Alzheimer's disease (AD). 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.ObjectiveWe 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.MethodsWe 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.ResultsThirty-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. APOE ε4 was present in 62.5%, including 10 ε4/ε4 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.ConclusionsSevere 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.PROSPERO registration no. CRD420251055067.
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APA 7th
Villarejo Galende, A., González-Sánchez, M., Hilario, A., Llamas-Velasco, S., Morenas-Rodríguez, E., Muñoz-García, M. I., et al. (2026). Severe symptomatic amyloid-related imaging abnormalities in Alzheimer's disease: Two case reports and systematic review of reported cases. Journal of Alzheimer's disease : JAD. https://doi.org/10.1177/13872877251404505
Vancouver
Villarejo Galende A, González-Sánchez M, Hilario A, Llamas-Velasco S, Morenas-Rodríguez E, Muñoz-García MI, et al. Severe symptomatic amyloid-related imaging abnormalities in Alzheimer's disease: Two case reports and systematic review of reported cases. Journal of Alzheimer's disease : JAD. 2026. doi:10.1177/13872877251404505. PMID: 41384832.
BibTeX
@article{villarejogalende2026-41384832,
author = {Villarejo Galende, A. and González-Sánchez, M. and Hilario, A. and Llamas-Velasco, S. and Morenas-Rodríguez, E. and Muñoz-García, M. I. and Ramos-González, A. and Pérez-Martínez, D. A. and others},
title = {{Severe symptomatic amyloid-related imaging abnormalities in Alzheimer's disease: Two case reports and systematic review of reported cases}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2026},
doi = {10.1177/13872877251404505},
pmid = {41384832},
url = {https://doi.org/10.1177/13872877251404505}
}
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Key findings
- Fifteen cases were associated with lecanemab, 10 with gantenerumab, 6 with donanemab, and 5 with other antibodies.
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Study details
- Study designsystematic review
- Effect size62.5%; 66.7%; 38.9%
- Evidence strengthHigh
How this study scored 79/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for sample size because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 46 of the 58 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41384832) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 46 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 46 of the 58 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
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