Clinical Challenges: Managing Cognitive Dysfunction in Multiple Sclerosis

Cognitive impairment affects an estimated 40-65% of all people living with multiple sclerosis (MS), and there are often deleterious effects on an individual’s ability to earn a living, care for their disease, and perform usual activities of daily living.

“There is evidence that MS affects information processing speed, visuospatial learning, working memory, and verbal fluency, even in the early stages of the disease,” Kathy Zackowski, PhD, OTR, senior director of Patient Management, Care, and Rehabilitation Research for the National MS Society, told MedPage Today. “The presence and extent of cognitive dysfunction in people with MS varies on the basis of several factors including disease course, disease duration, age, and disability.”

Cognitive impairment affects about one-third of patients with clinically isolated syndrome, about half of patients with relapsing-remitting MS (RRMS), and 80-90% of those with progressive MS, said John DeLuca, PhD, senior vice president of Research and Training at the Kessler Foundation in East Hanover, New Jersey, which is dedicated to helping people with disabilities regain function and achieve maximum independence

The National MS Society’s most recent (2018) guidelines recommend early baseline cognitive screening for adult and pediatric patients at least annually, using the same instrument each year, or more frequently if needed, Zackowski noted: “The Symbol Digit Modalities Test, a commonly used rapid assessment tool validated in children and adults with MS, is sensitive to changes in mental status during clinical relapses, when other clinical tests such as the Expanded Disability Status Scale may show no change.”

However, “most MS clinics in the U.S. do not provide any objective assessment of cognitive impairment, which is crucial over self-report,” she explained.

Regarding which patients may be at greatest risk, DeLuca said “evidence of cognitive impairment early in the disease is a huge predictor of cognitive decline down the road, as is the presence of gray matter volume loss. In newly diagnosed or early MS patients, these should be your cues to follow their cognitive progression more closely.”

Sarah Morrow, MD, director of the London MS Clinic at Western University in Ontario, agreed that early identification of cognitive symptoms is important: “Starting to discuss cognitive symptoms from diagnosis opens the door for persons with MS to feel comfortable bringing it to their neurologist’s attention,” she told MedPage Today. “We ask about changes in their cognitive and MS health at every visit.”

“At our clinic, our pilot study of a self-administered computer rehabilitation program, Cogmed Working Memory Training, suggested it improved attention/working memory and had a potential to improve mood in persons with MS,” Morrow said.

Another pilot study randomly assigned 61 people with MS to mindfulness meditation training, computerized adaptive cognitive training (ACT), or a waitlist control group. The investigators reported that not only did mindfulness significantly improve processing speed independent of baseline cognitive status, compared with ACT and control groups, but the team was able to extrapolate based on the early data to suggest that mindfulness training may also help MS patients regulate negative emotions.

The guidelines advise annual screening for depression, and Morrow noted that it can be difficult to separate cognitive symptoms from mood symptoms — especially depression and anxiety. Mood symptoms, which can lead persons with MS to have subjective feelings of cognitive impairment, have also been correlated with poor performance on cognitive tests, she added: “What is not clear is if this is a cause-and-effect relationship.”

DeLuca explained that depression might have a secondary dampening or demotivating effect on cognition — possibly due to a structural problem in the brain that may also affect cognition: “Identifying what is at play requires a proper neuropsychological assessment, to really look at the entire patient,” he said.

Treatment Approaches

There is as yet no “gold-standard” treatment for MS-related cognitive impairment, since there is limited evidence that disease-modifying therapies are effective in treating cognitive dysfunction, DeLuca and co-authors noted in a recent review. On the other hand, a significant body of data point to cognitive rehabilitation as a low-cost, low-risk, effective approach to treatment.

Unfortunately, though, cognitive rehab for persons with MS is not funded in either the U.S. or Canada, making such programs inaccessible to patients without private insurance, Morrow noted. “We do recommend that persons with MS continue to do cognitively stimulating tasks — such as reading, puzzles, cards games, etc.”

“There is a lot of evidence that cognitive reserve protects against cognitive decline in persons with MS,” she continued. “We also recommend exercise. There is weak evidence that exercise helps with cognition in persons with MS, but it is certainly beneficial for many other aspects of health as well.”

DeLuca noted that impaired processing speed is the most common cognitive deficit in people with MS, and has been the target of an increasing number of interventional studies.

In the review, he and his co-authors described small studies of several promising computerized, at-home cognitive rehabilitation programs. For example, BrainHQ significantly improved cognition composite scores compared with placebo, and was associated with “impressive” patient adherence across studies.

In addition, COGNI-TRAcK, which provides personalized working memory exercises, was associated in a small randomized clinical trial with post-treatment improvement in learning and memory, verbal fluency, attention, concentration, and processing speed — with the enhanced processing speed maintained 6 months later, the team noted.

The authors of a research update on the Can Do MS website, Abbey J. Hughes, PhD, of Johns Hopkins Medicine in Baltimore, and Pamela H. Miller, MA, CCC-SLP, a speech-language pathologist in Denver and Can Do MS programs consultant, praised the effectiveness of the (recently trademarked) Kessler Foundation-modified Story Memory Technique.

The 10-session memory rehabilitation program combines training in visualization and “context formation” to improve verbal learning and memory, and according to a review has shown effectiveness in three separate studies, including a brain imaging study that showed increased activity in brain regions involved in learning and memory, Hughes and Miller noted.

They added that MS studies also suggest “significant promise” for Attention Processing Training for improving attention, and RehaCom for improving general cognitive abilities.

“The challenge in cognitive rehabilitation may be finding the right specialist to refer patients to — i.e., with experience in MS as well as in cognitive rehabilitation,” DeLuca said. “That doesn’t mean we’re off the hook — it means we have to try harder. The data support cognitive rehabilitation. It’s time to get our MS patients with cognitive impairment the treatment they deserve.”

Exercise

“The best way to make exercise effective is to make it a prescribed treatment, and we’re far from that because we don’t know the best exercise or duration,” DeLuca noted. “Evidence has been mixed, largely because of methodologically weak studies.”

Zackowski said that although more study is needed, there is nonetheless “increasing evidence that physical exercise including aerobic training, resistance training, and balance training can be used to positively manage MS-related cognitive impairment.”

Some data show more cognitive benefits with aerobic exercise than with strength-training activities, noted DeLuca. “The work we’ve done on exercise suggests it has to be challenging, and if that challenge is a bit more aerobic, that’s a good thing. And just as more challenging cognitive exercises have a greater effect, physical exertion is [similarly] important.”

In a 2020 study, high-intensity interval training showed potentially greater effects on physical fitness and cognition — specifically verbal memory — compared with moderate continuous exercise, DeLuca noted. A post-hoc analysis of the findings showed significantly larger effects on verbal learning in participants with MS who had impaired versus intact cognition.

Research into the use of medications for cognitive issues in people with MS is ongoing, but the data so far are mixed, he said. “It can take 2 years to show an effect and it’s small, but medication could be considered for a patient showing cognitive problems early in the disease.”

Given the complexity of being human, there is no single best approach, DeLuca said. “Eventually, there will be three approaches to managing cognitive impairment: Medication, exercise, and some element of cognitive rehabilitation.”

Last Updated November 01, 2021