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Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease (Cochrane review)
Nonino F, Minozzi S, Sambati L, Del Giovane C, Baldin E, Bassi MC, et al.. Cochrane Database of Systematic Reviews, 2026-04-16
Topic: Amyloid, tau and blood-test diagnosis
Synthesis methods We meta-analysed results for each outcome within each comparison using the inverse variance method and the random-effects model. Included studies Overall, we included 17 studies with 20,342 participants. Synthesis of results Below, we report the results of the studies at 18 months. Cognitive function Compared to placebo, amyloid-beta-targeting monoclonal antibodies probably result in little to no difference in cognitive function as measured by the ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive) scale (standardised mean difference (SMD) -0.11, 95% confidence interval (CI) -0.16 to -0.06; 13 studies, 9895 participants; moderate certainty). Dementia severity Amyloid-beta-targeting monoclonal antibodies may result in little to no difference in dementia severity as measured by the CDR-SB (Clincal Dementia Rating Sum of Boxes) scale (SMD -0.12, 95% CI -0.24 to -0.00; 9 studies, 8053 participants; low certainty). Functional ability Amyloid-beta-targeting monoclonal antibodies probably result in little to no difference in functional ability as measured on the ADCS-ADL (Alzheimer's Disease Cooperative Study - Activities of Daily Living) scale (SMD 0.09, 95% CI 0.03 to 0.16; 3 studies, 3478 participants; moderate certainty) and may result in a small increase in functional ability if measured with the ADCS-iADL (Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living) scale (SMD 0.21, 95% CI 0.10 to 0.32; 1 study, 1252 participants; low certainty) or ADCS-ADL-MCI (Alzheimer's Disease Cooperative Study - Activities of Daily Living for Mild Cognitive Impairment) scale (SMD 0.23, 95% CI 0.12 to 0.33; 4 studies, 2802 participants; low certainty). Adverse events Amyloid-beta-targeting monoclonal antibodies probably result in a small increase in the occurrence of any ARIA E (ARD (absolute risk difference) 107 more per 1000, 95% CI 77 more to 148 more; 11 studies, 13,595 participants; moderate certainty) and probably little to no difference in symptomatic ARIA E (ARD 29 more per 1000, 95% CI 22 more to 38 more; 2 studies, 3522 participants; moderate certainty) or symptomatic ARIA H (ARD 4 more per 1000, 95% CI 1 fewer to 31 more; 1 study, 1795 participants; moderate certainty). Three studies assessing any ARIA H showed heterogeneous results (I 2 = 81%), which prevented pooled analysis. At 18 months, amyloid-beta-targeting monoclonal antibodies do not increase serious adverse events (ARD 6 more events per 1000, 95% CI 10 fewe
Key findings
- Synthesis methods We meta-analysed results for each outcome within each comparison using the inverse variance method and the random-effects model.
- Included studies Overall, we included 17 studies with 20,342 participants.
- Synthesis of results Below, we report the results of the studies at 18 months.
- Cognitive function Compared to placebo, amyloid-beta-targeting monoclonal antibodies probably result in little to no difference in cognitive function as measured by the ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive) scale (standardised mean difference (SMD) -0.11, 95% confidence interval (CI) -0.16 to -0.06; 13 studies, 9895 participants; moderate certainty).
- Dementia severity Amyloid-beta-targeting monoclonal antibodies may result in little to no difference in dementia severity as measured by the CDR-SB (Clincal Dementia Rating Sum of Boxes) scale (SMD -0.12, 95% CI -0.24 to -0.00; 9 studies, 8053 participants; low certainty).
Why it matters
This Cochrane review of 17 studies with 20,342 participants found that amyloid-beta-targeting monoclonal antibodies probably result in little to no difference in cognitive function and dementia severity at 18 months. It does not support these antibodies as a meaningful treatment for cognitive symptoms in people with mild cognitive impairment or mild dementia due to Alzheimer's disease.
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Study details
- Study designmeta-analysis
- Participants20,342
- Effect sizeADAS-Cog SMD -0.11 (95% CI -0.16 to -0.06); ARIA-E absolute risk difference +107 per 1,000
- Evidence strengthHigh
Limitations
Only one trial each of lecanemab and donanemab; functional unblinding from side effects may bias efficacy outcomes; all trials industry-funded; inconsistent outcome reporting.
How this study scored 76/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. We have no data on free to read, so that was left out: it earned 74 of the 98 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Cochrane Database of Systematic Reviews) |
| Journal's citation record | 3 / 4 | Cochrane Database of Systematic Reviews: journal h-index 468 (OpenAlex, 2026-10-29) |
| 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 | 20,342 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 | 3 / 7 | Cited 28 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 6 / 6 | Cited 116.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 28 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 0 / 4 | Last-listed author Edo Richard: h-index 4 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Amsterdam: institution h-index 1,209 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41985900) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 74 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 74 of the 98 points we could judge it on is 76 out of 100. |
| Total | 76 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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APA 7th
Nonino, F., Minozzi, S., Sambati, L., Del Giovane, C., Baldin, E., Bassi, M. C., et al. (2026). Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease (Cochrane review). Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD016297
Vancouver
Nonino F, Minozzi S, Sambati L, Del Giovane C, Baldin E, Bassi MC, et al. Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease (Cochrane review). Cochrane Database of Systematic Reviews. 2026. doi:10.1002/14651858.CD016297. PMID: 41985900.
BibTeX
@article{nonino2026-41985900,
author = {Nonino, F. and Minozzi, S. and Sambati, L. and Del Giovane, C. and Baldin, E. and Bassi, M. C. and others},
title = {{Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease (Cochrane review)}},
journal = {Cochrane Database of Systematic Reviews},
year = {2026},
doi = {10.1002/14651858.CD016297},
pmid = {41985900},
url = {https://doi.org/10.1002/14651858.CD016297}
}
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