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Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials
Zimmer JA, Ardayfio P, Wang H, Khanna R, Evans CD, Lu M, Sparks J, Andersen S, Lauzon S, Nery ESM, et al.. JAMA Neurology, 2025-05-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Amyloid-related imaging abnormalities (ARIA) are the major adverse event associated with amyloid-targeting immunotherapy. Results Across 3030 total participants (placebo-controlled trials: 999 placebo participants, 984 donanemab participants; open-label addendum: 1047 donanemab participants), mean (SD) age was approximately 73.7 (6.0) years and 1684 participants (55.6%) were female. Risk analysis demonstrated independent associations between ARIA-E and 6 baseline variables, including increased risk with APOE ε4 allele number, greater number of microhemorrhages, presence of cortical superficial siderosis, higher amyloid plaque, and elevated mean arterial pressure, and decreased risk with antihypertensive use. Conclusions and relevance ARIA is an adverse event associated with donanemab treatment that requires safety monitoring.
Key findings
- Importance Amyloid-related imaging abnormalities (ARIA) are the major adverse event associated with amyloid-targeting immunotherapy.
- Results Across 3030 total participants (placebo-controlled trials: 999 placebo participants, 984 donanemab participants; open-label addendum: 1047 donanemab participants), mean (SD) age was approximately 73.7 (6.0) years and 1684 participants (55.6%) were female.
- Risk analysis demonstrated independent associations between ARIA-E and 6 baseline variables, including increased risk with APOE ε4 allele number, greater number of microhemorrhages, presence of cortical superficial siderosis, higher amyloid plaque, and elevated mean arterial pressure, and decreased risk with antihypertensive use.
- Conclusions and relevance ARIA is an adverse event associated with donanemab treatment that requires safety monitoring.
Why it matters
This analysis of donanemab trials found that amyloid-related imaging abnormalities (ARIA) are an adverse event associated with donanemab treatment that requires safety monitoring. Several baseline factors were linked to higher or lower risk of ARIA-E.
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Study details
- Study designphase-3-trial
- Participants3,030
- Effect sizeARIA-E 24.4% vs 1.9% placebo; symptomatic ARIA-E 5.8%; serious ARIA-E 1.5%
- Evidence strengthHigh
Limitations
Industry-sponsored secondary analysis; trial populations exclude many real-world patients (for example those on anticoagulants); open-label addendum lacked tau inclusion criteria.
How this study scored 83/100
Published in a leading specialty journal, and it is a large phase 3 trial. We have no data on free to read, so that was left out: it earned 81 of the 98 points we could judge it on, which is 83 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA Neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A large phase 3 trial |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 3,030 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 170 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 56.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 93.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 21 other studies in this library |
| Still being cited | 3 / 4 | Cited 170 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author John Randall Sims: h-index 41 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40063015) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 81 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 81 of the 98 points we could judge it on is 83 out of 100. |
| Total | 83 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2025.0065
- PubMed: 40063015
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Zimmer, J. A., Ardayfio, P., Wang, H., Khanna, R., Evans, C. D., Lu, M., et al. (2025). Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.0065
Vancouver
Zimmer JA, Ardayfio P, Wang H, Khanna R, Evans CD, Lu M, et al. Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials. JAMA Neurology. 2025. doi:10.1001/jamaneurol.2025.0065. PMID: 40063015.
BibTeX
@article{zimmer2025-40063015,
author = {Zimmer, J. A. and Ardayfio, P. and Wang, H. and Khanna, R. and Evans, C. D. and Lu, M. and Sparks, J. and Andersen, S. and Lauzon, S. and Nery, E. S. M. and others},
title = {{Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials}},
journal = {JAMA Neurology},
year = {2025},
doi = {10.1001/jamaneurol.2025.0065},
pmid = {40063015},
url = {https://doi.org/10.1001/jamaneurol.2025.0065}
}
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