Will behavioral treatments for cognitive impairment in multiple sclerosis become standards-of-care?

Cognitive impairment is common and debilitating in persons with multiple sclerosis (MS), and further is poorly-managed by pharmacotherapy. Cognitive rehabilitation and exercise training have been identified as promising behavioral approaches for managing MS-related cognitive impairment based on systematic reviews and meta-analyses. However, each body of literature is associated with similar sets of methodological shortcomings, as has been identified by periodic systematic reviews and meta-analyses. Thus, there is little generalizability or transportability research supporting either behavioral approach for managing cognitive dysfunction in this population under real-world conditions (i.e., as a standard-of-care). To that end, this paper aims to catalyze the advancement of cognitive rehabilitation and exercise training research in MS, respectively, towards the successful implementation of generalizability/transportability trials. This first involves critical examinations of the respective cognitive rehabilitation and exercise training literatures in MS from a chronological perspective, with particular emphasis on how the fields have each evolved in response to systematic reviews and meta-analyses. Accordingly, the current paper then provides a roadmap for harmonizing research in those areas to systematically and efficiently inform the development of generalizability/transportability trials for behavioral approaches to manage MS-related cognitive dysfunction. This involves the recognition of overlapping facilitators and impediments for progress in each field, including considerations for the implementation of neuroimaging. Ultimately, the provision of such a framework aims to shorten the timeline for research to influence clinical practice and improve the lives of cognitively-impaired persons with MS.