Treatment and management of cognitive dysfunction in patients with multiple sclerosis

Abstract

Cognitive impairment is a common and devastating manifestation of multiple sclerosis (MS). Although disease-modifying therapies have been efficacious for reducing relapse rates in MS, such treatments are ineffective for treating cognitive dysfunction. Alternative treatment approaches for mitigating cognitive problems are greatly needed in this population. To date, cognitive rehabilitation and exercise training have been identified as possible candidates for treating MS-related cognitive impairment; however, cognitive dysfunction is still often considered to be poorly managed in patients with MS. This Review provides a comprehensive overview of recent developments in the treatment and management of cognitive impairment in people with MS. We describe the theoretical rationales, current states of the science, field-wide challenges and recent advances in cognitive rehabilitation and exercise training for treating MS-related cognitive impairment. We also discuss future directions for research into the treatment of cognitive impairment in MS that should set the stage for the inclusion of cognitive rehabilitation and exercise training into clinical practice within the next decade.

Key points

  • Cognitive deficits are common in people with multiple sclerosis (MS) and have a substantial impact on daily life functioning; effective treatment of such deficits is essential.

  • Studies examining the efficacy of cognitive rehabilitation in MS have become more frequent in recent years and a few effective cognitive rehabilitation programmes for individuals with MS have been identified.

  • Research on exercise training as a promising approach for improving cognition in MS has been growing, but more research is necessary.

  • Insufficient evidence is currently available to support pharmacological approaches for treating cognitive impairment in patients with MS.

  • Research is needed on factors such as the treatment timing, dosage and duration, and the impact of treatment on everyday life in patients with MS.

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Fig. 1: Literature on cognitive rehabilitation and exercise training in multiple sclerosis.
Fig. 2: Cognitive rehabilitation in multiple sclerosis.

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Acknowledgements

The preparation of this paper was supported by the Kessler Foundation and the University of Alabama at Birmingham. The preparation of this paper was not supported by an externally funded grant award.

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Each author contributed equally to researching data for the article and wrote the sections of the manuscript that fell within their area of expertise (J.D.: cognitive impairment in MS and imaging; N.D.C.: cognitive rehabilitation; B.M.S.: exercise). All authors edited the manuscript in its entirety and provided comments and suggestions prior to submission.

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Correspondence to John DeLuca.

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Supplementary information

Glossary

Processing speed

The rate at which the brain is able to take in information, process it and give an appropriate response.

Executive functioning

A set of cognitive processes necessary for the cognitive control of behaviour, including monitoring behaviours that facilitate the attainment of chosen goals.

Working memory

A cognitive process that involves storing, focusing attention on and manipulating information for a relatively short period of time (such as a few seconds).

Cognitive rehabilitation

A systematically applied set of medical and therapeutic services designed to improve cognitive functioning and participation in activities that might be affected by difficulties in one or more cognitive domains.

Exercise training

Planned, structured, repetitive physical activity performed to improve or maintain one or more aspects of physical fitness.

Neuroplasticity

The ability of the brain to form and reorganize synaptic connections, especially in response to learning or experience or following injury.

Functional connectivity

The temporal correlation between the time series of different brain regions or the presence of statistical dependence between two sets of neurophysiological data.

Effective connectivity

The influence of one neural system over another, either at a synaptic or a cortical level.

Cognitive reserve

The extent to which the brain can sustain damage, as from Alzheimer disease, stroke, alcohol overuse or head injury, for example, without affecting intellectual capacity.

n-back

A continuous performance task often used to measure working memory capacity. The participant is presented with a sequence of letters and must indicate when the current stimulus matches the one occurring n steps earlier. The load factor n can be adjusted to make the task more or less difficult (for example, 1-back, 2-back, 3-back).

Trait conscientiousness

The degree to which an individual is conscientious as a personality trait. Conscientiousness refers to being careful or diligent, or having a desire to do a task well. Individuals high on persistence are considered ambitious and perfectionistic and demonstrate a determination and tenacity to achieve a goal. Such descriptions are most consistent with the trait of conscientiousness.

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DeLuca, J., Chiaravalloti, N.D. & Sandroff, B.M. Treatment and management of cognitive dysfunction in patients with multiple sclerosis. Nat Rev Neurol 16, 319–332 (2020). https://doi.org/10.1038/s41582-020-0355-1

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