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Incidence, severity, and associated risk factors for amyloid-related imaging abnormalities in anti-amyloid monoclonal antibody therapy for early Alzheimer's disease: a systematic review and meta-analysis
Martinez Holst MA, Sierra Valiente AM, Garcia-Becerra CA.. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2026-10-02
Topic: Amyloid, tau and blood-test diagnosis
Background Amyloid-related imaging abnormalities (ARIA) are the most concerning side effect of the treatment for early Alzheimer's disease (AD) with anti-amyloid monoclonal antibodies (mAbs). Objective This study systematically evaluates the incidence, severity, and associated risk factors of ARIA in patients with early AD receiving anti-amyloid mAbs therapy. Methods A comprehensive systematic review and meta-analysis were conducted following PRISMA guidelines. Assessed outcomes included ARIA incidence, symptomatic cases and severity, radiographic severity, and risk factors. Pooled incidences and odds ratios were estimated with a random effects model using the R software (version 4.5.2). Results The systematic search yielded a total of 20 articles, representing 21 phase 3 randomized controlled trials that involved 12,610 AD patients. Pooled incidence was 5.4% for ARIA-E and 10.27% for ARIA-H. Most cases being asymptomatic and radiographically mild to moderate. Risk factor analysis revealed that ApoE 4 homozygotes carriers (OR = 5.12), ApoE 4 heterozygotes carriers (OR = 1.91), higher mAb dosage (OR = 2.0) and baseline microhemorrhages (OR = 1.43) had a major influence on ARIA-E occurrence, as for ARIA-H incidence was higher in ApoE 4 heterozygous (OR = 1.65) and homozygotes carriers (OR = 4.65). Moreover, ApoE 4 heterozygous and homozygotic carriers were associated with symptomatic (OR = 1.52;3.68) and severe radiographic (OR = 2.11;6.31) ARIA-E. Discussion ARIA remains a significant safety concern in anti-amyloid mAb therapy, with incidence and severity influenced by genetic, neuroimaging, and treatment-related factors. Future research should focus on refining risk stratification and understanding long-term consequences of ARIA.
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APA 7th
Martinez Holst, M. A., Sierra Valiente, A. M., & Garcia-Becerra, C. A. (2026). Incidence, severity, and associated risk factors for amyloid-related imaging abnormalities in anti-amyloid monoclonal antibody therapy for early Alzheimer's disease: a systematic review and meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. https://doi.org/10.1007/s10072-026-09430-5
Vancouver
Martinez Holst MA, Sierra Valiente AM, Garcia-Becerra CA. Incidence, severity, and associated risk factors for amyloid-related imaging abnormalities in anti-amyloid monoclonal antibody therapy for early Alzheimer's disease: a systematic review and meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2026. doi:10.1007/s10072-026-09430-5. PMID: 42825842.
BibTeX
@article{martinezholst2026-42825842,
author = {Martinez Holst, M. A. and Sierra Valiente, A. M. and Garcia-Becerra, C. A.},
title = {{Incidence, severity, and associated risk factors for amyloid-related imaging abnormalities in anti-amyloid monoclonal antibody therapy for early Alzheimer's disease: a systematic review and meta-analysis}},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
year = {2026},
doi = {10.1007/s10072-026-09430-5},
pmid = {42825842},
url = {https://doi.org/10.1007/s10072-026-09430-5}
}
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Key findings
- Results The systematic search yielded a total of 20 articles, representing 21 phase 3 randomized controlled trials that involved 12,610 AD patients.
- Risk factor analysis revealed that ApoE 4 homozygotes carriers (OR = 5.12), ApoE 4 heterozygotes carriers (OR = 1.91), higher mAb dosage (OR = 2.0) and baseline microhemorrhages (OR = 1.43) had a major influence on ARIA-E occurrence, as for ARIA-H incidence was higher in ApoE 4 heterozygous (OR = 1.65) and homozygotes carriers (OR = 4.65).
- Moreover, ApoE 4 heterozygous and homozygotic carriers were associated with symptomatic (OR = 1.52;3.68) and severe radiographic (OR = 2.11;6.31) ARIA-E.
- Discussion ARIA remains a significant safety concern in anti-amyloid mAb therapy, with incidence and severity influenced by genetic, neuroimaging, and treatment-related factors.
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Study details
- Study designsystematic review
- Participants20
- Effect size5.4%; 10.27%; OR = 5.12
- Evidence strengthHigh
How this study scored 83/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. 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 48 of the 58 points we could judge it on, which is 83 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology) |
| 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 | 1 / 4 | 20 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 42825842) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 48 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 48 of the 58 points we could judge it on is 83 out of 100. |
| Total | 83 / 100 | — |
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