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Cognitive dysfunction is a well-recognized feature of multiple sclerosis (MS) that can be detected even in benign and pediatric cases. No evidence-based recommendations are available for the treatment of MS-related cognitive problems. Acetylcholinesterase inhibitors are used off-label in MS, on the basis of positive findings from several small-scale clinical trials reported primarily in abstract form. In the largest published trial (69 patients with MS), donepezil improved verbal learning and memory (J Neurol Sci 2006; 245:127). Intuitively, studying other medications approved for dementia, such as the N-methyl-d-aspartic acid (NMDA) receptor inhibitor memantine, might make sense. Moreover, memantine was proposed as a potential therapy for …