Efficacy of acetylcholinesterase inhibitors for cognitive impairment in multiple sclerosis: A systematic review and meta-analysis

Background & Objective: Multiple Sclerosis (MS) is a chronic demyelinating condition characterized by a myriad of neurologic deficits. The prevalence rate of Cognitive impairment (CI) ranges from 40 to 60 percent among community-dwelling individuals with MS. Cholinergic dysfunction is one of the different mechanisms proposed to cause CI, supporting the use of acetylcholinesterase inhibitors (AChEIs) in certain conditions. The study aims to determine the safety and efficacy of acetylcholinesterase inhibitors in multiple sclerosis patients with cognitive impairment through a review of randomized clinical trials. Methods: Using the updated PRISMA guidelines, we searched gov website, Google Scholar, and HERDIN Database for relevant studies until November 15, 2022. Results: A total of 73 records were identified and five studies were included in the analysis. Pooled evidence shows that AchEIs (donepezil 10 mg/day or rivastigmine 10 mg/day for 12 to 14 weeks) did and sustained attention and the Selective Reminding Test (SRT) score for verbal memory. Another study using the Weschler Memory Scale (WMS) also did not show significant improvement in their scores. However, a recent trial that used the Everyday memory questionnaire (EMQ), prospective and retrospective memory questionnaire (PRMQ), and the Digit span test (DST) showed significant difference between pre- and post-intervention mean scores in the donepezil group (p<0.001). The physical and mental health scores of the Multiple Sclerosis Quality of Life questionnaires (MSQOL) significantly improved in MS patients receiving donepezil. Both donepezil and rivastigmine were associated with non-serious adverse events. Conclusion: The use of AchEIs among MS patients does not significantly improve objective measures of cognition but has positive impact on subjective scales of cognition (EMQ and PRMQ). AchEIs were shown to improve patients' quality of life. AchEIs are safe and well tolerated among MS patients.