There is general consensus regarding the benefit of acetylcholinesterase inhibitors (e.g. donepezil) in Alzheimer's disease (AD). However, the combined effect of acetylcholinesterase and cognitive stimulation therapy (CST) is still controversial. This study examines their combined effect on the progression of cognitive decline in AD by comparing the cognitive performance of 17 AD patients treated with CST and donepezil (combined treatment group) and 13 AD patients treated with donepezil alone (control group). Patients in the combined treatment group received 5 mg of donepezil per day and about 20 one-hour CST sessions for one year, whereas the control group received only 5 mg of donepezil per day. The first eight sessions were carried out once a week, and subsequent sessions were generally once every two weeks. The patients were evaluated for changes in cognitive ability by administering the Mini-mental State Examination (MMSE) before the start of CST (baseline) and about one year later (follow-up). A repeated-measure analysis of variance revealed a significant group x time interaction. The MMSE score decreased significantly in the control group, but did not change significantly in the combined treatment group. Three patients in the control group declined by four points on the MMSE, compared to none in the combined treatment group. Effect size (ES) in the control group was relatively large and negative, while the ES in the combined treatment group was close to zero. The results suggest the possibility that donepezil plus CST slowed the rate of cognitive decline more than the administration of donepezil alone.