This randomized study evaluated the combined effect of a cognitive-communication program plus an acetylcholinesterase inhibitor (donepezil; donepezil-plus-stimulation group; n = 26), as compared with donepezil alone (donepezil-only group; n = 28) in 54 patients with mild to moderate Alzheimer's disease (AD; Mini-Mental Status Examination score of 12- 28) ranging in age from 54 to 91 years. It was hypothesized that cognitive-communication stimulation in combination with donepezil would positively affect the following: (a) relevance of discourse, (b) performance of functional abilities, (c) emotional symptoms, (d) quality of life, and (e) overall global function, as measured by caregiver and participant report and standardized measures. Cognitive-communication, neuropsychiatric, functional performance, and quality of life evaluations were conducted at baseline and Month 4, the month after the 2-month active stimulation period. Follow-up evaluations were performed at Months 8 and 12. The stimulation program consisted of 12 hr of intervention over an 8-week period and involved participant-led discussions requiring homework, interactive sessions about AD, and discussions using salient life stories. Additive effects of active stimulation with donepezil were examined in 2 ways: (1) comparing mean group performance over time and (2) evaluating change scores from baseline. A Group x Time interaction was found for the donepezil-plus-stimulation group in the emotional symptoms of apathy and irritability as compared with the donepezil-only group. Evaluation of change scores from baseline to 12 months revealed a positive effect for the donepezil-plus-stimulation group on discourse and functional abilities with a trend on apathy, irritability, and patient-reported quality of life. In sum, the research revealed benefits to the donepezil-plus-stimulation group in the areas of discourse abilities, functional abilities, emotional symptoms, and overall global performance. This study adds to growing evidence that active cognitive stimulation may slow the rate of verbal and functional decline and decrease negative emotional symptoms in AD when combined with acetylcholinesterase inhibitors, indicating a need to advance research in the area of cognitive treatments. The fact that AD is a progressive brain disease should not preclude ameliorative treatment.