Impact of Pharmacotherapy on Cognitive Dysfunction in Patients with Multiple Sclerosis

Cognitive impairment is a common symptom of multiple sclerosis (MS), adversely impacting many spheres of daily functioning. Yet the effectiveness of pharmacological interventions for cognitive impairment in MS is unclear. Clinicians and patients alike would benefit from formal guidelines regarding effective management of cognitive symptoms. We reviewed the background on the measurement, pathophysiology and risk factors for cognitive dysfunction in MS, and then examined the published clinical trials of pharmacotherapy, including both disease-modifying treatments (DMTs) and symptom-management therapies (SMTs). Our review of DMTs revealed only a single well-designed, randomized, controlled trial where intramuscular interferon (IFN)-β1a, administered once weekly, was compared with placebo. The results showed significant benefits in terms of cognitive processing speed and memory. Less convincing but promising data have shown the potential benefits of IFN-β_1b and natalizumab. The literature on SMTs is replete with placebo-controlled, single-centre studies, with a failure to replicate initially promising results. The results for SMTs such as acetylcholinesterase inhibitors and psychostimulants are mixed. Some encouraging data show promise but not to a threshold of indication for standard clinical use. Numerous methodological factors hamper research in this area. Acknowledging the lack of firm conclusions, we argue that all DMTs are likely to benefit cognition and that, if otherwise safe, SMTs with some empirical support may be attempted at the discretion of the treating clinician. We offer some guidance on the assessment and monitoring of cognitive function to inform off-license treatment of cognitive impairment in MS patients.