Treatment persistence with acetylcholinesterase inhibitors in Alzheimer's disease: Real-world evidence from a retrospective cohort study

Abstract

Background

Alzheimer's disease (AD) is the leading cause of dementia worldwide, yet long-term persistence with acetylcholinesterase inhibitors remains suboptimal in routine practice.

Objective

To compare real-world treatment persistence among patients with mild to moderate AD receiving oral donepezil, rivastigmine capsules, or transdermal rivastigmine patches, and to identify factors influencing discontinuation.

Methods

In this retrospective cohort study, 1062 patients aged ≥65 years with newly diagnosed AD were identified from a hospital registry between 2015 and 2019 and followed through 2021. Treatment persistence was evaluated by duration and 1-year continuation rates. Discontinuation was defined as a prescription gap exceeding 90 days. Multivariable Cox proportional hazards models were used to identify predictors of discontinuation.

Results

Patients receiving donepezil had significantly longer mean treatment duration (3.03 years) and higher 1-year continuation rates (66.2%) than those receiving rivastigmine capsules (1.81 years, 39.9%) or patches (1.43 years, 45.5%). Both rivastigmine formulations were independently associated with greater discontinuation risk (adjusted hazard ratio [aHR] 1.44 and 1.76, respectively; p < 0.001). Participation in a national dementia care program was the strongest protective factor, associated with a 69% lower discontinuation risk (aHR 0.31; p < 0.001). Higher baseline CASI scores, younger age, and milder cognitive impairment predicted greater persistence, whereas adverse events markedly increased discontinuation.

Conclusions

Donepezil demonstrated superior real-world persistence compared with rivastigmine. Structured dementia care programs substantially enhanced treatment continuity, underscoring the importance of both pharmacologic choice and system-level support in sustaining long-term therapy in AD.