Cognitive Fatigability is Independent of Subjective Cognitive Fatigue and Mood in Multiple Sclerosis

Why is this study important?

If asked to name the most debilitating symptom associated with their disease, different people with multiple sclerosis (MS) will likely name different types of impairment that limit their daily functioning. Among these, cognitive fatigue is an invisible symptom that can cause a myriad of issues because of its interference with mentally-demanding tasks. Because cognitive fatigue related to MS is a subjective experience, different people describe it in different ways, using wording such as “mental fog,” lack of energy, or total exhaustion. Health care providers have long struggled to quantify this subjective symptom, with the aim of helping people with MS to manage fatigue more effectively and to improve their quality of life.

How is cognitive fatigue assessed in individuals with MS?

Health care providers typically use subjective questionnaires to determine to what extent people with MS experience cognitive fatigue. However, the answers to these questionnaires are not ideal for measuring the effects of treatment on MS-related fatigue. In recent years, researchers have studied the merits of more objective clinical tools, which assess what is known as “cognitive fatigability.” These usually consist of sustained attention tests similar to those used to diagnose attention-deficit/hyperactivity disorder (ADHD). Some MS experts have expressed concern about the inability of such tests to capture the subjective fatigue experienced by many individuals with MS, and to detect a possible overlap between MS-related fatigue and symptoms of mood disorders.

Amidst the ongoing debate over the best method for measuring MS-related fatigue, researchers at the MS Center of the Aristotle University of Thessaloniki, Greece compared the results of a typical test used to measure cognitive fatigability with those of questionnaires used to evaluate subjective fatigue and mood. This study included 120 people with MS, with ages ranging from 20 to 50 years, who presented for routine follow-up visits at the outpatient clinic of the MS center. The participants took a sustained attention test that is typically used to diagnose ADHD in adults, and then answered questions used to screen for depression and fatigue. The subjective fatigue questionnaire included questions about different types of impairment, including physical, cognitive, and psychosocial fatigue.

The results showed that cognitive fatigability, which was defined as a decline in performance during the 20-minute sustained attention test, did not necessarily reflect subjective fatigue. Forty-five participants (37.5%) had scores that indicated subjective fatigue, but this finding did not overlap with a decline in performance during the attention test. Such decline was mostly seen in the older participants who had long-standing MS and higher degrees of disability.

Does depression play a role in MS-related fatigue?

Mood disorders were present in approximately half of the people with MS in the Aristotle University study. Most of the participants had some degree of depression, and nearly 16% were severely depressed. The researchers noted that there was a connection between the depression scores and the subjective fatigue findings, suggesting that mood may influence fatigue in MS. The presence of cognitive fatigue in people with MS should alert health care providers and caregivers to the possibility of underlying depression.

Is there an ideal way to measure cognitive fatigue in MS?

Because the mechanisms of chronic fatigue in MS are largely unknown, many questions remain to be answered, including whether depression symptoms overlap with those of cognitive fatigue.

In the Aristotle University study, cognitive fatigability tests confirmed that mental fatigue worsens with age and with advanced disease stage, but they were not a good measure of subjective fatigue or of its psychosocial components. Another tool that may help gauge mental fatigue is a neuroimaging study of changes that occur in the brain, which are associated with cognitive decline. The Greek researchers studied the brain MRI scans available from half of the participants, which showed that such structural and functional changes were more frequent in people with advanced stages of MS. However, more research is needed to confirm whether mental fatigue in MS reflects a failure of the cognitive circuits involved in attention.

While efforts to measure MS-related fatigue accurately continue, paying close attention to the subjective (and therefore often vague) symptoms experienced by individuals with MS is key to ensuring the best care and support for them.  If people with MS experience what they believe to be symptoms of cognitive fatigue, they should share them with their healthcare provider. 

Original Article