Home › Research › Treatments
Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer's disease: a target trial emulation
Lee CY, Hsu CW, Tseng PT, Fang YY, Stubbs B, Thompson T, Carvalho AF, Lin YH et al.. Alzheimer's research & therapy, 2026-06-22
Topic: Amyloid, tau and blood-test diagnosis
Background Acetylcholinesterase inhibitors (AChEIs) provide symptomatic relief in Alzheimer's disease (AD), whereas lecanemab may modify disease progression; however, real-world evidence on its safety and clinical impact remains limited. Therefore, this study aimed to compare the safety and effectiveness of initiating lecanemab versus AChEIs in patients with mild cognitive impairment (MCI) or AD. Methods Using the TriNetX US electronic health record network, we conducted a retrospective cohort study including individuals diagnosed with MCI or AD between July 2023 and September 2025. A target trial emulation with 1:1 propensity score matching and Cox models estimated comparative risks. Results Lecanemab was associated with a fivefold higher incidence of neuroimaging abnormalities than AChEIs, while 1-year treatment persistence was similar (53.4% vs 52.5%). After matching, 589 patients were included in each cohort. Compared with AChEIs, lecanemab was associated with significantly lower risks of behavioral and psychological symptoms of dementia (BPSD) (HR, 0.52; 95% CI, 0.36-0.77) and emergency visits (HR, 0.66; 95% CI, 0.51-0.85), but a higher risk of hospitalization (HR, 1.31; 95% CI, 1.03-1.67). Lecanemab was also associated with lower use of antipsychotics (HR, 0.47; 95% CI, 0.32-0.70), antidepressants (HR, 0.60; 95% CI, 0.43-0.85), melatonin/orexin antagonists (HR, 0.61; 95% CI, 0.42-0.88), antibiotics (HR, 0.61; 95% CI, 0.44-0.86), and antifungals (HR, 0.57; 95% CI, 0.37-0.88), whereas steroid use was higher among lecanemab users (HR, 2.19; 95% CI, 1.55-3.10). Conclusions Compared with an AChEI-based conventional care strategy, lecanemab initiation was associated with comparable treatment persistence and lower observed risks of BPSD, emergency visit as well as reduced use of psychotropic and infection-related medications in exploratory analyses. However, the higher incidence of neuroimaging abnormalities associated with lecanemab, along with increased risks of hospitalization and corticosteroid use, likely reflects proactive clinical monitoring and management of amyloid-related imaging abnormalities (ARIA). While residual confounding cannot be excluded and results warrant cautious interpretation, these exploratory findings warrant further validation in biomarker-confirmed cohorts and head-to-head randomized trials.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Lee, C. Y., Hsu, C. W., Tseng, P. T., Fang, Y. Y., Stubbs, B., Thompson, T., et al. (2026). Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer's disease: a target trial emulation. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-026-02095-4
Vancouver
Lee CY, Hsu CW, Tseng PT, Fang YY, Stubbs B, Thompson T, et al. Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer's disease: a target trial emulation. Alzheimer's research & therapy. 2026. doi:10.1186/s13195-026-02095-4. PMID: 42332768.
BibTeX
@article{lee2026-42332768,
author = {Lee, C. Y. and Hsu, C. W. and Tseng, P. T. and Fang, Y. Y. and Stubbs, B. and Thompson, T. and Carvalho, A. F. and Lin, Y. H. and others},
title = {{Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer's disease: a target trial emulation}},
journal = {Alzheimer's research \& therapy},
year = {2026},
doi = {10.1186/s13195-026-02095-4},
pmid = {42332768},
url = {https://doi.org/10.1186/s13195-026-02095-4}
}
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.
Key findings
- Therefore, this study aimed to compare the safety and effectiveness of initiating lecanemab versus AChEIs in patients with mild cognitive impairment (MCI) or AD.
- Results Lecanemab was associated with a fivefold higher incidence of neuroimaging abnormalities than AChEIs, while 1-year treatment persistence was similar (53.4% vs 52.5%).
- Compared with AChEIs, lecanemab was associated with significantly lower risks of behavioral and psychological symptoms of dementia (BPSD) (HR, 0.52; 95% CI, 0.36-0.77) and emergency visits (HR, 0.66; 95% CI, 0.51-0.85), but a higher risk of hospitalization (HR, 1.31; 95% CI, 1.03-1.67).
- Lecanemab was also associated with lower use of antipsychotics (HR, 0.47; 95% CI, 0.32-0.70), antidepressants (HR, 0.60; 95% CI, 0.43-0.85), melatonin/orexin antagonists (HR, 0.61; 95% CI, 0.42-0.88), antibiotics (HR, 0.61; 95% CI, 0.44-0.86), and antifungals (HR, 0.57; 95% CI, 0.37-0.88), whereas steroid use was higher among lecanemab users (HR, 2.19; 95% CI, 1.55-3.10).
- Conclusions Compared with an AChEI-based conventional care strategy, lecanemab initiation was associated with comparable treatment persistence and lower observed risks of BPSD, emergency visit as well as reduced use of psychotropic and infection-related medications in exploratory analyses.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Study designcohort study
- Participants589
- Effect size53.4%; 52.5%
- Evidence strengthHigh
How this study scored 78/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomized / blinded 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 multicenter collaboration, so those were left out: it earned 45 of the 58 points we could judge it on, which is 78 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A cohort study following people over time |
| 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 | 2 / 4 | 589 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42332768) |
| Free to read | 2 / 2 | Free to read |
| Points | 45 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 45 of the 58 points we could judge it on is 78 out of 100. |
| Total | 78 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Treatments
Also tagged “emulation”
2 studies in the library carry the topic tag “emulation”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 2 tagged studies.