Cognition Issues in Multiple Sclerosis Are Vital to Address

NeurologyLiveNovember 2022
Volume 5
Issue 6

Cognitive problems have been reported to occur in as many as 7 in 10 individuals with MS, yet they remain a difficult and undertreated challenge in clinical care.

John DeLuca, PhD Senior Vice President for Research and Training, Kessler Foundation Professor, Department of Physical Medicine and Rehabilitation, and Department of Neurology, Rutgers New Jersey Medical School, Newark

John DeLuca, PhD

MULTIPLE SCLEROSIS (MS) IS THE most common disabling neurologic disease affecting young adults, with symptom onset generally between ages 20 and 40 years, affecting 2.2 million adults worldwide.1 Cognitive problems are observed in as many as 70% of persons with MS. This means that on average, 2 of every 3 patients in MS clinics are experiencing some degree of cognitive dysfunction.2 Although highly individualized in presentation, the most common problems are in cognitive processing speed and learning and memory, although impairments also can be observed in executive functions, visuospatial processing, and social cognition. Cognitive problems can be observed early in the course of the disease but typically are more prevalent later. Roughly one-third of patients with clinically isolated syndrome (CIS) experience cognitive decline. Approximately 50% of patients with relapsing-remitting MS (RRMS) and 80% to 90% of patients with progressive MS show evidence of cognitive impairment.3

Cognitive dysfunction can have a significant impact on everyday functional activities including, for example, employment, driving, social and family activities, household chores, financial management, everyday tasks (eg, internet use), adherence to medication regimens, and overall quality of life, all beyond the physical disability. Assessment, treatment, and management of cognitive impairment in MS are crucial.

The Importance of Assessing Cognitive Dysfunction

Knowledge of a patient’s cognitive status gives the clinician critical information for management. Imagine the value to care if the clinician had a test that could predict disease progression from CIS to RRMS, from RRMS to secondary progressive MS (SPMS), and within the course of SPMS. In addition, suppose the test could predict decline in disability (ie, Expanded Disability Status Scale [EDSS] scores) and cognitive worsening, could detect brain atrophy and axonal damage, and could assess problems in everyday functional activities along with clinical factors such as adherence to treatment.

In fact, cognitive testing can provide such information to the clinician. For example, recent studies have shown that, independent of physical disability, patients with MS who were not cognitively impaired and scored at the highest quartile on a screening test for cognition (ie, Symbol Digit Modalities Test [SDMT]) earned more than twice the income of those who scored at the lowest quartile; the latter were more than 3 times more likely to be receiving financial support though social benefits.4 Cognitive impairment at diagnosis predicts time to reach EDSS score of 4 and conversion to SPMS 10 years later.5 Change in cognitive status is significantly associated with loss of employment and deterioration in employment status 3.5 years6 and 7 years later,7 respectively. In a recent study, cognitive dysfunction was associated with significantly higher odds of progressing from RRMS to SPMS (odds ratio, 2.29) and a significantly higher hazard of death (HR, 3.07), even after adjusting for other covariates.8 These are just some examples of the predictive power of knowing the cognitive status of a patient with MS, underscoring the importance of early screening and treatment.

How to Assess Cognition

The neurologist examination and assessment are offer no greater than a chance likelihood of correctly identifying cognitive impairment in persons with MS,9 and thus are insufficient for an accurate diagnosis. Why not just ask the patient? Numerous studies have shown that patient self-reporting typically does not accurately reflect actual cognitive dysfunction nor its impact on everyday activities. Rather, patient self-reporting largely reflects emotional distress.10 Although self-reporting from significant other or care partner is better, actual objective testing is the most accurate way of identifying cognitive impairment.

Cognitive impairment is influenced by age, gender, cognitive reserve, psychiatric factors, personality, medications, cannabis use, and medical history (eg, learning disability, prior neurological problems, diabetes, etc). Consequently, accurate diagnosis can only be assured via a comprehensive neuropsychological evaluation that takes such individual factors into account. Unfortunately, objective assessment is rare in neurological clinics. For example, a study found that more than 50% of MS clinics do not assess for cognitive problems at all, whereas 19% rely on self-reporting, with less than one-third of all clinics doing any type of formal screening or testing.11 Although things have improved somewhat more recently, having no formal procedures for assessing cognitive impairment remains commonplace in practice.12 Thus, objective assessment of cognitive impairment should be part of the standard care of patients with MS.

When to Assess for Cognitive Impairment

The National Multiple Sclerosis Society has published guidelines for cognitive screening and management in persons with MS.13 These guidelines (TABLE13) state that comprehensive cognitive care requires improved education about cognition for health care providers, patients with MS, and their families; baseline cognitive screening and annual reassessments; baseline depression screening and annual reassessments; a more comprehensive cognitive evaluation for those who fail the screening; and remedial interventions by appropriately trained professionals.

Click the image to enlarge.

Click the image to enlarge.

Similar guidelines for early and annual cognitive assessment have been recommended by the American Academy of Neurology14; the National Institute for Health and Care Excellence in the United Kingdom15; consensuses of Italian,16 Greek,17 and Spanish MS professionals18; and regular cognitive follow-up by agreement among Canadian professionals.19 Clearly there is an international movement acknowledging that the time has come for cognitive assessment and management to become standard of care for this patient population.

Treatment for Cognitive Impairment in MS After more than 3 decades of research, there is considerable evidence that cognitive rehabilitation (CR) approaches can significantly improve cognitive impairment in MS.20 CR includes various behavioral treatments designed to help patients improve their cognitive functions and daily living activities. The most recent Cochrane Review examined 44 randomized control trials (RCTs) consisting of 2714 patients with MS and concluded that “there is low evidence to support the use of memory rehabilitation in people with MS.”21

Memory rehabilitation significantly improved patients’ subjective memory; verbal, visual, and working memory; cognitive processing speed; depression; and quality of life. There is growing evidence that cognitive processing speed can also be significantly improved with cognitive rehabilitation approaches.22 Various compensatory cognitive interventions have been shown to be effective and generally result in medium to large effect sizes. The Kessler Foundation Modified Story Memory Technique is an approach with considerable evidence for improving not only cognitive processing but also improving everyday life activities, doing so through changes in functional brain activity.23,24 Several other compensatory techniques have also been shown to be effective.22 Restorative approaches to treatment tend to utilize computer-based interventions and have proven effective, although the overall effect size has tended to be small.25

Exercise as a behavioral approach to improving cognitive functioning has been gaining prominence in the past decade, with preliminary data showing promise. However, to date, the data remain mixed at best and additional research is needed before such intervention can be recommended. Finally, pharmacological treatment for cognitive impairment is also mixed at best. There is little to no evidence from RCTs that disease-modifying therapies (DMTs) improve cognitive processing. When there is an effect, it is small,26,27 even in the more recent high-efficacy medications.28,29 Symptomatic medications tend to have a better effect on cognition than DMTs, but here, too, the results are mixed at best.26


About 150 years ago, Jean-Martin Charcot revealed that cognitive problems were a feature of MS. Yet, in the 1970s it was thought that only 3% to 5% of persons with MS experienced cognitive impairment. We know today that most patients with MS experience some degree of cognitive dysfunction, which can have a devastating impact on everyday life. Yet, even today, most MS centers do little to nothing regarding screening for cognitive impairment, and fewer still offer treatment recommendations. Given what we know from the extensive literature on cognition in MS, it is now time to make cognitive assessment and treatment standard of care for patients with MS.

However, it is acknowledged that barriers to optimal care must be addressed. First, there is still insufficient knowledge on the prevalence, scope, and impact of cognitive dysfunction, even among health care professionals who are typically more adept on pharmacological opportunities. There is a reluctance to discuss cognitive symptoms on the part of clinicians who may feel they do not have the referral options, time, or expertise to address such issues, and patients who feel embarrassed or afraid to report changes for various reasons (eg, threatened employment, etc). Other barriers include an insufficient number of trained clinicians to do screening, testing, and/or remediation; inadequate reimbursement for screening and treatment; and inadequate financial resources for MS centers to hire appropriate staff. Despite these challenges, it is incumbent upon us as clinicians to address these barriers as best we can so that patients with MS can receive the assessment, care, and treatment they deserve.

Conflicts of interest/competing interests: Dr John DeLuca received consulting fees/honorarium from Biogen, Sanofi Genzyme, Novartis, and Bristol Myers Squibb. He has received grant funding from Biogen, EMD Serono, National Multiple Sclerosis Society, Consortium of Multiple Sclerosis Centers, and the National Institutes of Health.

Correspondence: John DeLuca;; 1199 Pleasant Valley Way, West Orange, NJ 07052; Phone: (973) 324-3572

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