Cognition in multiple sclerosis: State of the field and priorities for the future

Abstract

Cognitive decline is recognized as a prevalent and debilitating symptom of multiple sclerosis (MS), especially deficits in episodic memory and processing speed. The field aims to (1) incorporate cognitive assessment into standard clinical care and clinical trials, (2) utilize state-of-the-art neuroimaging to more thoroughly understand neural bases of cognitive deficits, and (3) develop effective, evidence-based, clinically feasible interventions to prevent or treat cognitive dysfunction, which are lacking. There are obstacles to these goals. Our group of MS researchers and clinicians with varied expertise took stock of the current state of the field, and we identify several important practical and theoretical challenges, including key knowledge gaps and methodologic limitations related to (1) understanding and measurement of cognitive deficits, (2) neuroimaging of neural bases and correlates of deficits, and (3) development of effective treatments. This is not a comprehensive review of the extensive literature, but instead a statement of guidelines and priorities for the field. For instance, we provide recommendations for improving the scientific basis and methodologic rigor for cognitive rehabilitation research. Toward this end, we call for multidisciplinary collaborations toward development of biologically based theoretical models of cognition capable of empirical validation and evidence-based refinement, providing the scientific context for effective treatment discovery.

Figure. Cognitive decline from previous functioning

About half of persons with multiple sclerosis are considered cognitively impaired in prevalence studies, which is based on performance below a chosen threshold (yellow arrows crossing −1.5 SDs). As illustrated, however, patients may experience and report notable decline from previous function without crossing the threshold into impairment (red arrows), although such decline likely affects real-world functioning. For example, the uppermost red arrow represents a person with above average cognition prior to disease onset (84th percentile). Despite a decline of 1.5 SD, this person's current performance is within the average range (dark blue shaded area), and she or he would be categorized as cognitively intact in research studies. Clinically, this person may be told that he or she does not have impairment, which conflicts with his or her real experience of decline.