Long‐term cognitive benefits of donepezil in Alzheimer’s disease: A retrospective comparison between 1994–1999 and 2000–2004

Objective: In order to address an issue of how long Alzheimer’s disease (AD) patients should receive donepezil, we estimated long‐term effect of donepezil on cognition as well as its influential factors. We also evaluated the additional effect of cerebrospinal fluid (CSF)‐tau protein levels on diagnosis. Methods: We compared cognitive changes between current (2000–2004) AD patients (donepezil users) and previous AD patients, seen by us 1994–1999, without receiving donepezil (non‐donepezil users) by a mixed effect model. Cognition was assessed by Mini‐Mental State Examination (MMSE) at 6‐month intervals up to 24 months. Sensitivity analysis was performed exclusively on patients with high CSF‐tau protein levels (CSF‐tau >330 pg/mL) to minimize inaccuracies of the diagnosis Results: From 495 AD patients reviewed, 192 patients (120 donepezil users and 72 controls) were eligible. Estimated annual decline of MMSE was 1.2 points (95% confidence interval (95%CI), 0.9–1.5) in the donepezil users, whereas it was 2.8 points (95%CI, 2.1–3.6) in the control group. The difference was statistically significant (P < 0.001). The sensitivity analysis demonstrated that these declines were 1.2 (95%CI, 0.8–1.6) and 3.1 (95%CI, 2.3–3.9) points in the donepezil users and control groups, respectively. Conclusions: Long‐term donepezil use for at least 2 years appeared to be beneficial in maintaining cognition in AD patients. As the cholinergic central nervous system consistently degenerates over time, long‐term use of donepezil may be an appropriate therapy. Discontinuation of donepezil may not be recommended as far as patients are in a stable condition.