Higher Levels of MS Fatigue Linked to Poorer Cognitive Skills

People with multiple sclerosis (MS) who report higher levels of fatigue are more likely to have lower performance scores in tests that evaluate cognitive skills, a study from Ireland suggests.

Specifically, poor verbal learning abilities, visual-spatial memory, and information processing speed (IPS) were associated with higher levels of self-reported fatigue in MS patients.

IPS is the amount of time a person needs to take in information, process it, and then react to solve a problem or complete a task.

“The present study highlights the importance of considering fatigue when exploring cognitive difficulties in MS and ensuring holistic screening assessments are part of routine clinical care for [people with MS],” the researchers wrote.

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The study, “Interpreting the clinical importance of the relationship between subjective fatigue and cognitive impairment in multiple sclerosis (MS): how BICAMS performance is affected by MS-related fatigue,” was published in the journal Multiple Sclerosis and Related Disorders.

Fatigue a common MS symptom

Fatigue, defined as a feeling of constant tiredness and/or lack of physical and mental energy, affects about 70% to 90% of people with MS. Many patients describe fatigue as the disease’s worst symptom.

Many also have cognitive difficulties, which can impact their social relationships, work, and independence in activities of daily living. IPS, memory, attention, and executive functioning skills, such as the ability to make plans and multitask, are generally affected.

Whether a relationship between self-reported fatigue and cognitive skills exists in MS remains unclear largely due to inconsistent results from previous studies.

“The multifaceted and complex nature of MS-related fatigue, in combination with the large [variability] of interventions and methodologies used in its study may explain the discrepant findings,” the researchers wrote.

However, “there is greatest evidence for an association between fatigue and IPS,” they added. Additionally, according to a hypothesis called the Relative Consequence Mode, impairments in other complex cognitive processes in MS are due to IPS deficits.

A research team in Dublin examined the relationship between MS patient-reported fatigue and cognitive function, including IPS, and explored the Relative Consequence Model.

The study included 192 adults with MS who were recruited at an MS center in Dublin between December 2018 and January 2021. None had experienced an MS relapse within the previous month, had other neurological conditions, pre-existing learning difficulties, or were on medications that could affect the workings of the brain and spinal cord.

Patients’ mean age was 42.9 (range, 22–81); 69.3% were woman and 30.7% were men. Most participants (80.2%) had relapsing-remitting MS, 9.4% had secondary progressive MS, and 4.2% primary progressive MS. The mean MS disease duration was 9.53 years.

Physical, cognitive, and psychosocial fatigue was assessed with the patient-reported Modified Fatigue Impact Scale. Cognitive function was measured through the Brief International Cognitive Assessment for MS (BICAMS), a test made up of three assessments.

These include the Symbol Digit Modalities Test (SDMT) for processing speed, the California Verbal Learning Test-II (CVLT-II) for verbal learning, and the Brief Visuospatial Memory Test Revised (BVMT-R) for visual-spatial learning and memory.

Results showed that 57.8% of the participants had clinical fatigue, while 76% showed deficits in at least one of the BICAMS tests.

Patient-report fatigue levels link with cognitive test scores

Analysis showed that, in general, higher levels of total patient-reported fatigue, as well as physical, cognitive, and psychosocial fatigue, all significantly associated with poorer performance in each of the three BICAMS cognitive tests.

Higher levels of physical fatigue were most strongly associated with lower IPS, while patients reporting greater cognitive fatigue were more likely to have lower verbal and visual-spatial learning abilities.

“The strongest correlation with total fatigue was with verbal learning,” the researchers wrote.

When adjusting for IPS, the team found that the link between fatigue and verbal, as well as visual, learning weakened. However, greater cognitive fatigue was still significantly associated with lower verbal and visual learning. Higher levels of total fatigue also remained significantly linked to verbal learning, but not visual learning.

These findings “provide partial evidence for the Relative Consequence Model,” the team wrote, suggesting that IPS may mediate the link between subjective fatigue and objective visual learning performance, but not objective verbal learning performance.

“Subjective fatigue and objective cognitive performance in MS are related,” the researchers wrote, and this “may imply that subjective fatigue can have a negative impact on objective cognitive performance in [people with MS].”

As such, in MS patients with high levels of fatigue, “caution is advised in the interpretation of BICAMS scores,” the team wrote, and “more detailed neuropsychological assessments may be required to accurately highlight objective cognitive impairment independent of subjective fatigue.”

When the two co-exist at high levels, “efforts of cognitive rehabilitation may be assisted through the supplemental implementation of fatigue-based interventions such as cognitive rehabilitation therapy,” they added.

“It is our hope that future research may advance these findings with controls for mood and disability in mind,” the researchers concluded.