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Comparative risk of amyloid-related imaging abnormalities with anti-amyloid-β monoclonal antibodies: A systematic review and penalized likelihood network meta-analysis of randomized trials
Sharma A, Suresh V, Kola PR, Raj R, Javairia F, Nithyanandam A, Kaur A, Arora H et al.. Journal of Alzheimer's disease : JAD, 2026-07-11
Topic: Amyloid, tau and blood-test diagnosis
BackgroundAnti-amyloid-β monoclonal antibodies represent a new class of disease-modifying therapies for Alzheimer's disease (AD). Their clinical adoption is complicated by amyloid-related imaging abnormalities (ARIA), encompassing vasogenic edema (ARIA-E) and hemorrhagic changes (ARIA-H). The comparative ARIA risk across agents and the influence of genetic factors remain incompletely characterized.ObjectiveTo quantify the pooled incidence of ARIA-E and ARIA-H associated with anti-amyloid-β immunotherapies and to compare relative risks across agents using network meta-analytic modeling.MethodsFollowing PRISMA guidelines (PROSPERO: CRD420250653157), we searched PubMed, EMBASE, Scopus, Web of Science, and Ovid through January 2026 for Phase II/III randomized controlled trials of anti-amyloid-β immunotherapies in AD. Random-effects models estimated pooled prevalence and odds ratios (ORs). A penalized likelihood network meta-analysis addressed sparse events. APOE ε4-stratified analyses and Bayesian sensitivity models were also performed.ResultsTwenty-two trials (up to 23,120 participants) were included. Pooled ARIA-E prevalence was 6.8% and ARIA-H was 15.8%, with substantial heterogeneity. Anti-amyloid-β therapy significantly increased odds of ARIA-E (OR 7.93; 95% CI 4.50-13.98) and ARIA-H (OR 1.87; 95% CI 1.28-2.72) versus placebo. The highest ARIA-E risk was seen with donanemab and aducanumab, followed by gantenerumab and lecanemab. APOE ε4 carriage significantly elevated ARIA-E (OR 2.28) and ARIA-H (OR 2.07) risk, with a clear gene-dose effect in homozygotes.ConclusionsARIA risk varies substantially across anti-amyloid-β therapies and is strongly modulated by APOE ε4 status. These findings support genotype-informed risk stratification and individualized MRI monitoring to optimize the benefit-risk balance of disease-modifying therapies in AD.
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APA 7th
Sharma, A., Suresh, V., Kola, P. R., Raj, R., Javairia, F., Nithyanandam, A., et al. (2026). Comparative risk of amyloid-related imaging abnormalities with anti-amyloid-β monoclonal antibodies: A systematic review and penalized likelihood network meta-analysis of randomized trials. Journal of Alzheimer's disease : JAD. https://doi.org/10.1177/13872877261466097
Vancouver
Sharma A, Suresh V, Kola PR, Raj R, Javairia F, Nithyanandam A, et al. Comparative risk of amyloid-related imaging abnormalities with anti-amyloid-β monoclonal antibodies: A systematic review and penalized likelihood network meta-analysis of randomized trials. Journal of Alzheimer's disease : JAD. 2026. doi:10.1177/13872877261466097. PMID: 42434897.
BibTeX
@article{sharma2026-42434897,
author = {Sharma, A. and Suresh, V. and Kola, P. R. and Raj, R. and Javairia, F. and Nithyanandam, A. and Kaur, A. and Arora, H. and others},
title = {{Comparative risk of amyloid-related imaging abnormalities with anti-amyloid-β monoclonal antibodies: A systematic review and penalized likelihood network meta-analysis of randomized trials}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2026},
doi = {10.1177/13872877261466097},
pmid = {42434897},
url = {https://doi.org/10.1177/13872877261466097}
}
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Key findings
- The comparative ARIA risk across agents and the influence of genetic factors remain incompletely characterized.ObjectiveTo quantify the pooled incidence of ARIA-E and ARIA-H associated with anti-amyloid-β immunotherapies and to compare relative risks across agents using network meta-analytic modeling.MethodsFollowing PRISMA guidelines (PROSPERO: CRD420250653157), we searched PubMed, EMBASE, Scopus, Web of Science, and Ovid through January 2026 for Phase II/III randomized controlled trials of anti-amyloid-β immunotherapies in AD.
- Anti-amyloid-β therapy significantly increased odds of ARIA-E (OR 7.93; 95% CI 4.50-13.98) and ARIA-H (OR 1.87; 95% CI 1.28-2.72) versus placebo.
- APOE ε4 carriage significantly elevated ARIA-E (OR 2.28) and ARIA-H (OR 2.07) risk, with a clear gene-dose effect in homozygotes.ConclusionsARIA risk varies substantially across anti-amyloid-β therapies and is strongly modulated by APOE ε4 status.
- These findings support genotype-informed risk stratification and individualized MRI monitoring to optimize the benefit-risk balance of disease-modifying therapies in AD.
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Study details
- Study designmeta-analysis
- Participants23,120
- Effect size6.8%; 15.8%; OR 7.93
- Evidence strengthHigh
How this study scored 88/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. 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 51 of the 58 points we could judge it on, which is 88 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 meta-analysis pooling many studies |
| 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 | 4 / 4 | 23,120 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 42434897) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 51 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 51 of the 58 points we could judge it on is 88 out of 100. |
| Total | 88 / 100 | — |
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