Discontinuing cholinesterase inhibitors in Alzheimer's disease: evidence from France's reimbursement withdrawal

Evidence before this study

We searched PubMed with the terms “donepezil”, “rivastigmine”, “galantamine”, “cholinesterase inhibitors”, and “Alzheimer's disease” for articles published in English or French up to December 2025. Randomised controlled trials of cholinesterase inhibitors mainly reported short-term cognitive benefits of 6 months, with few studies extending to 12 months. Long-term randomised trials were lacking or limited by high attrition and methodological complexity. Evidence from observational cohorts suggested potential long-term benefits, but these studies were prone to indication and selection bias.

Added value of this study

Our study leveraged the unique policy-driven withdrawal of reimbursement for cholinesterase inhibitors in France to emulate a “stop trial” under real-world conditions. Using two large databases, we compared cognitive trajectories and mortality between continuers and discontinuers. Our findings of a consistent, detrimental effect of discontinuation on cognition, equivalent to a 6- to 12-month delay in decline, recapitulate and extend those of earlier trials in a more representative population.

Implications of all the available evidence

Taken together, the evidence indicates that cholinesterase inhibitors provide modest but sustained symptomatic benefits in Alzheimer's disease, particularly when treatment is continued. Despite concerns regarding adverse effects, discontinuation appears to accelerate cognitive decline without a survival benefit. These findings support reconsidering France's reimbursement policy and reinforce the relevance of symptomatic treatments in the era of disease-modifying therapies.

Source: The Lancet Regional Health – Europe