Unmet Need of Cognitive Decline in Patients With Multiple Sclerosis
The neuropsychological aspects of multiple sclerosis (MS), including cognitive dysfunction, are some of the most disabling symptoms of the disease, and they negatively impact quality of life for patients. During the course of MS, approximately 50% of patients experience cognitive deficits that may affect short-term memory, concentration, visuospatial function, executive function, and sensory function. Cognitive decline can become apparent early in the course of MS. A recent study that used neuropsychological assessment showed that approximately 50% of the patients with MS and very mild physical disability had cognitive impairment with a primary involvement of the prefrontal cognitive functions. However, cognitive impairment is more prevalent among patients with the progressive forms of the MS than patients with relapsing-remitting MS. Patients with pediatric-onset MS may also be at risk for cognitive dysfunction, and for this population of patients there are long-term implications for social adjustment, employment, and well-being. It is now recognized that MS produces pathological lesions of gray matter that have consequences for cognitive functions in patients with MS.
Rehabilitation early in the disease course has been shown to improve cognitive abilities. Results of another recent study showed that patients with clinically stable relapsing-remitting MS and mild to moderate cognitive impairment who received computer-assisted functional cognitive training, compared with standard clinical care, demonstrated significant improvements in verbal and visuospatial episodic memory, processing speed/attention, and executive functioning from pre-assessment to post-assessment. Early detection of cognitive dysfunction followed by cognitive rehabilitation may reduce or delay cognitive decline in patients with MS.
Professor and Chair
“There is no doubt that most patients with MS ultimately will have measurable cognitive dysfunction that seems directly attributable to the disease, and that needs to be a target for therapy in treating our patients, and for further study in clinical trials.”
Cognitive decline or cognitive dysfunction is a very important outcome that researchers and clinicians treating patients with MS should be paying attention to. It is challenging to measure this outcome because it usually requires detailed neuropsychological testing to understand whether a patient’s reports of cognitive dysfunction are likely to be primarily related to the disease or whether those reports might be influenced by other things, such as depression or anxiety, sleep disorders, or medications. There is no doubt that most patients with MS ultimately will have measurable cognitive dysfunction that seems directly attributable to the disease, and that needs to be a target for therapy in treating our patients, and for further study in clinical trials. Cognitive dysfunction is associated with physical disability, including walking impairment, and with magnetic resonance imaging findings, which are some of the leading outcome measures for progressive MS trials. So, successful therapies in progressive forms of MS will need to demonstrate benefits for cognitive dysfunction to be convincing. The paucity of published clinical trials that assessed cognitive dysfunction accentuates this unmet need for patients with MS.
Benedict RHB, DeLuca J, Enzinger C, Geurts JJG, Krupp LB, Rao SM. Neuropsychology of multiple sclerosis: looking back and moving forward. J Int Neuropsychol Soc. 2017;23(9-10):832-842.
Charvet LE, Cleary RE, Vazquez K, Belman AL, Krupp LB; US Network for Pediatric MS. Social cognition in pediatric-onset multiple sclerosis (MS). Mult Scler. 2014;20(11):1478-1484.
Mehr SR, Zimmerman MP. Reviewing the unmet needs of patients with multiple sclerosis. Am Health Drug Benefits. 2015;8(8):426-431.
Messinis L, Nasios G, Kosmidis MH, et al. Efficacy of a computer-assisted cognitive rehabilitation intervention in relapsing-remitting multiple sclerosis patients: a multicenter randomized controlled rrial. Behav Neurol. 2017; 2017: 5919841. doi: 10.1155/2017/5919841.
Migliore S, Ghazaryan A, Simonelli I, et al. Cognitive impairment in relapsing-remitting multiple sclerosis patients with very mild clinical disability. Behav Neurol. 2017;2017: 7404289. doi: 10.1155/2017/7404289.
Sumowski JF, Benedict R, Enzinger C, et al. Cognition in multiple sclerosis: state of the field and priorities for the future. Neurology. 2018;90(6):278-288.