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Long-term effect of discontinuing anticholinesterase treatment on cognitive decline and mortality in Alzheimer's disease in France: a quasi-experiment and target trial emulation study
Lecerf Simon, Guinebretiere Octave, Bentegeac Raphaël, Gauthier Victoria, Aymes Estelle, Mekkaoui Chaymae, Dumurgier Julien, Amouyel Philippe et al.. The Lancet regional health. Europe, 2026-02-24
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
In 2018, France withdrew reimbursement for cholinesterase inhibitors (ChEIs) in Alzheimer's disease, citing modest efficacy, lack of long-term benefit, and safety concerns. This policy shift provided a unique opportunity to assess ChEI effectiveness in real-world settings, by evaluating, among patients treated with ChEI between 01/08/2017 and 01/08/2018, the impact of treatment discontinuation on cognitive decline (MMSE score) and survival. Using the French National Alzheimer's Database (BNA) and Meotis databases, we emulated a pragmatic, intention-to-treat trial comparing patients who discontinued ChEIs after delisting to those who continued treatment, under quasi-experimental conditions. To model cognitive trajectories, we used the inverse probability treatment-weighted (IPTW) cohort and applied mixed-effects models with random intercepts across all follow-up visits. Survival was estimated with a pooled logistic regression including treatment group, follow-up time, and an interaction between treatment and time. The mean difference in MMSE decline between discontinuers and continuers after one year was 0·97 points (95% CI 0·68-1·27, p < 0·001), reaching 1·81 points (0·91-2·71, p < 0·001), after four years. No significant difference in mortality (RR 1·10, 95% CI [0·95-1·29]) was observed over a five-year period. Our findings confirm and extend prior trials by demonstrating the sustained cognitive benefits of ChEIs in a real-world setting. While acknowledging the limitations associated with its retrospective nature, our study argues for reconsidering the 2018 delisting decision, as ChEIs remain safe and clinically relevant for mild-to-moderate Alzheimer's disease. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
What this study adds
Evidence grade: Moderate
This study found that people with mild-to-moderate Alzheimer's disease who stopped cholinesterase inhibitors after France removed reimbursement declined more on MMSE scores than those who continued, but it found no significant difference in mortality over five years. The authors argue for reconsidering the 2018 delisting decision, while acknowledging the study's retrospective limitations.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Simon, L., Octave, G., Raphaël, B., Victoria, G., Estelle, A., Chaymae, M., et al. (2026). Long-term effect of discontinuing anticholinesterase treatment on cognitive decline and mortality in Alzheimer's disease in France: a quasi-experiment and target trial emulation study. The Lancet regional health. Europe. https://doi.org/10.1016/j.lanepe.2026.101607
Vancouver
Simon L, Octave G, Raphaël B, Victoria G, Estelle A, Chaymae M, et al. Long-term effect of discontinuing anticholinesterase treatment on cognitive decline and mortality in Alzheimer's disease in France: a quasi-experiment and target trial emulation study. The Lancet regional health. Europe. 2026. doi:10.1016/j.lanepe.2026.101607. PMID: 41732331.
BibTeX
@article{simon2026-41732331,
author = {Simon, Lecerf and Octave, Guinebretiere and Raphaël, Bentegeac and Victoria, Gauthier and Estelle, Aymes and Chaymae, Mekkaoui and Julien, Dumurgier and Philippe, Amouyel and others},
title = {{Long-term effect of discontinuing anticholinesterase treatment on cognitive decline and mortality in Alzheimer's disease in France: a quasi-experiment and target trial emulation study}},
journal = {The Lancet regional health. Europe},
year = {2026},
doi = {10.1016/j.lanepe.2026.101607},
pmid = {41732331},
url = {https://doi.org/10.1016/j.lanepe.2026.101607}
}
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Key findings
- No significant difference in mortality (RR 1·10, 95% CI [0·95-1·29]) was observed over a five-year period.
- Our findings confirm and extend prior trials by demonstrating the sustained cognitive benefits of ChEIs in a real-world setting.
- While acknowledging the limitations associated with its retrospective nature, our study argues for reconsidering the 2018 delisting decision, as ChEIs remain safe and clinically relevant for mild-to-moderate Alzheimer's disease.
Why it matters
This study found that people with mild-to-moderate Alzheimer's disease who stopped cholinesterase inhibitors after France removed reimbursement declined more on MMSE scores than those who continued, but it found no significant difference in mortality over five years. The authors argue for reconsidering the 2018 delisting decision, while acknowledging the study's retrospective limitations.
Study details
- Evidence strengthModerate
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Lancet regional health. Europe) |
| Journal's citation record | 1 / 4 | The Lancet Regional Health - Europe: journal h-index 88 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-17) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Thibaud Lebouvier: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Centre National de la Recherche Scientifique: institution h-index 2,529 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41732331) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
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