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The Challenge of Cognitive Changes in Multiple Sclerosis

— About half of all people with MS will have cognitive symptoms due to the disease

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Key Points

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Cognitive impairment is a recognized sequela of the demyelinating disorder multiple sclerosis (MS). Various studies have attempted to quantify the percentage of patients with cognitive impairment in each MS phenotype. range from 34% to 90% depending on the research setting and the disease course. In general, half of all people with MS will experience cognitive symptoms due to the disease, and cognitive decline is more common in the progressive phenotypes.

of the pathophysiology of cognitive impairment in MS found that information processing speed, attention, learning, and memory are the most frequently involved domains. Deficits in executive function and visuospatial processing are also reported, but less frequently.

Although both white and gray matter have been implicated in the pathophysiology of cognitive decline in MS, the brain's focal and diffuse gray matter damage has been consistently identified as being among the best predictors of cognitive deficits, the review noted.

"Using double inversion recovery sequence, higher number and volume of cortical lesions, especially in the hippocampus, were found to be significantly associated with the severity of cognitive dysfunction and to predict worsening of cognitive performance over 5 years," the authors wrote. "Moreover, more severe atrophy and microstructural abnormalities of cognitively relevant gray matter regions such as the thalamus, hippocampus, cortex, and cerebellum have been consistently identified among the best contributors of worse cognitive performance in MS patients with the main disease clinical phenotypes, and to predict cognitive deterioration up to 13 years."

How Disease-Modifying Therapies (DMTs) Help Protect Cognition

Cognitive deficits can occur in the early stages of MS, even in the absence of other neurological deficits. For example, Mariusz Stasiolek, MD, PhD, of Medical University of Lodz in Poland, and colleagues noted in a that "it is assumed that cognitive dysfunction is already present in the early stage of the disease, even in patients with CIS [clinically isolated syndrome]."

Additionally, cognitive performance appears to be a potential predictive marker of disease progression and a patient's future employment status and quality of life. "Identifying cognitive impairment at the earliest stages should be a crucial part of the assessment of the patient's clinical status. Consequently, when diagnosed at an early stage, cognitive dysfunction may suggest implementing highly effective DMTs and focusing on cognitive rehabilitation in addition to promoting a healthy lifestyle," Stasiolek and co-authors said.

Tirisham Gyang, MD, of the Ohio State University Wexner Medical Center in Columbus, emphasizes the importance of good disease control for cognitive health: "Cognitive changes often occur early in the disease process, so it's extremely important to make sure the MS is very well controlled via an effective DMT to address existing inflammation and prevent new inflammation," she told MedPage Today. "That will often limit the effects of MS-related cognitive challenges."

Exercise also plays an important role in helping to maintain cognition in MS. reviewed the specific types of exercise that are recommended, along with caveats about safety concerns and possible barriers.

Best Practices in Cognitive Screening

In 2018, the National Multiple Sclerosis Society convened experts in cognitive dysfunction to review available evidence and reach consensus on the optimal strategies for screening, monitoring, and treating cognitive changes.

In addition to advocating for increased professional and patient education about the prevalence, impact, and appropriate management of cognitive symptoms, the group issued the following :

  • For adults and children (8+ years of age) with clinical or magnetic resonance imaging evidence of neurologic damage consistent with MS: As a minimum, early baseline screening with the Symbol Digit Modalities Test (SDMT) or similarly validated test, when the patient is clinically stable; and annual re-assessment with the same instrument, or more often as needed to (1) detect acute disease activity; (2) assess for treatment effects (e.g., starting/changing a DMT) or for relapse recovery; (3) evaluate progression of cognitive impairment; and/or (4) screen for new-onset cognitive problems.
  • For adults (≥18 years): More comprehensive assessment for anyone who tests positive on initial cognitive screening or demonstrates significant cognitive decline, especially if there are concerns about comorbidities or if the individual is applying for disability due to cognitive impairment.
  • For children (<18 years): Neuropsychological evaluation for any unexplained change in school functioning (academic or behavioral).
  • Remedial interventions/accommodations for adults and children to improve functioning at home, work, or school.

About the SDMT

Although other screening instruments are available, the recommendations specifically favor the use of the for routine cognitive screenings. The test, which has been validated in children ages 8 and older, takes less than 5 minutes and can be used in the clinic setting. It uses a specific number/abstract symbol coding task to measure processing speed. Patients must demonstrate elements of attention, visual-perceptual processing, working memory, and cognitive/psychomotor speed to complete the SDMT.

The test is sensitive to changes in mental status during clinical relapses involving evidence of cognitive change and during isolated cognitive relapses without changes on the Expanded Disability Status Scale.

Given the widespread reliance on the SDMT in the MS clinic, various researchers have explored of the test, with the aim of increasing patient engagement by using familiar technology.

Cognitive Rehabilitation

There are currently no pharmacological agents that directly treat or reduce the effects of cognitive dysfunction in MS. Instead, physicians should refer patients with cognitive concerns to neuropsychologists for in-depth assessment and cognitive rehabilitation.

During a neuropsychological cognitive evaluation, a patient's cognitive functioning is evaluated using a variety of assessments. This will provide specific information about any cognitive deficits and can help to identify other conditions that may contribute to cognitive problems, such as medication side effects, mood disorders, and sleep issues. Other causes of cognitive dysfunction should be ruled out by the clinician managing MS.

Cognitive rehabilitation, which must be carefully tailored to each patient, typically uses both restorative and compensatory strategies. Restorative techniques include the use of memory aids like mnemonics and multisensory inputs. Compensatory strategies often include training in how to limit distractions, avoid sensory overload, and completing one thought or activity before starting another.

Wendy Ann Longley, PhD, a neuropsychologist at Uniting War Memorial Hospital in Waverley, New South Wales in Australia, that research findings that support the effectiveness of cognitive rehabilitation in MS continue to advance at a rapid pace, and called the results encouraging.

"Cognitive rehabilitation is a relatively low-cost and low-risk intervention; patients typically report enjoying it, and because of the lack of approved pharmacological treatments, it is the best option to treat cognitive impairment in MS," she said.

Gyang said she supports early referral for neuropsychological assessment when patients present with cognitive concerns. "In our center, we have a very low threshold for cognitive assessment referrals because otherwise it's very difficult to know for sure that a patient's cognitive challenges are MS-related," she said. "Once a neuropsychologist performs baseline testing, we can monitor that patient to see if the cognitive dysfunction is getting worse over time."

Read previous installments in this series:

Part 1: Early Diagnosis Can Mean Better Outcomes in Multiple Sclerosis

Part 2: How Does Multiple Sclerosis Start?

Part 3: The Deep and Multidimensional Connection Between Multiple Sclerosis and Depression

Part 4: Case Study: Sudden Blurred Vision in a Young Woman

Part 5: Early Aggressive Treatment May Work Best in Newly Diagnosed Multiple Sclerosis

Part 6: How Progressive Multiple Sclerosis Differs From Relapsing-Remitting MS