Effects of donepezil on memory and cognition in multiple sclerosis

Acetylcholinesterase inhibitors are used to treat dementia associated with Alzheimer's disease, but their cognitive benefits may extend to additional disorders such as multiple sclerosis (MS). A single-center double-blind placebo-controlled randomized clinical trial evaluated the effectiveness of donepezil in a sample of 69 MS persons selected for initial memory difficulties. Subjects received neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in total recall on the Selective Reminding Test, a measure of verbal learning and memory. Secondary outcomes included other neuropsychological tests from the Brief Repeatable Battery, patient-reported change in memory, and physician-reported impression of cognitive change. Donepezil improved memory performance on the SRT compared to placebo. This benefit remained significant after controlling for various covariates including Expanded Disability Status Scale (EDSS), MS subtype, interferon beta use, treatment group beliefs, gender, baseline selected reminding test (SRT) score, and reading ability. Subjects on donepezil were more likely to report memory improvement (65.7%) than those on placebo (32.4%). The clinician also reported cognitive improvement in more donepezil (54.3%) than placebo (29.4%) subjects. No serious adverse events related to study medication occurred. However, more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams. Donepezil improved learning and memory in MS patients with initial cognitive difficulties in a single-center clinical trial. Replication of results in a larger multi-center investigation is warranted in order to more definitively assess the efficacy of this intervention.