What predicts cognitive fatigue in MS?

Do you want to make sense of cognitive fatigue? Then this post is for you. 

Arch Clin Neuropsychol. 2018 Feb 17. doi: 10.1093/arclin/acy014. [Epub ahead of print]

Predictive Models of Cognitive Fatigue in Multiple Sclerosis.

Berard JA, Smith AM, Walker LAS.


Cognitive fatigue (CF) can be defined as decreased performance with sustained cognitive effort. The present study examined the interrelatedness of disease severity, fatigue, depression, and sleep quality in order to evaluate their predictive roles of CF in MS. Four theoretical models examining these variables were assessed.


Fifty-eight individuals with a diagnosis of MS were recruited. CF was measured by examining last third versus first third performance on the Paced Auditory Serial Addition Test (PASAT). The PASAT and self-report measures of fatigue, depression, and sleep quality were administered. Path analysis was used to evaluate each of the models.


CF was correlated only with depression (r = .362, p = .006) and sleep quality (r = .433, p = .001). Sleep quality was the greatest significant independent predictor of CF (β = .433, t(1,55) = 3.53, p < .001), accounting for 17.3% of the total variance. The best fitting model showed sleep quality as the largest contributor to CF; however, depression played a smaller predictive role. Furthermore, depression emerged as the strongest predictor of sleep quality and fatigue. Disease severity weakly predicted depression.


Sleep quality is the most significant predictor of CF in MS. As such, sleep quality may be a treatable cause of CF. Sleep quality itself, however, accounted for only 17.3% of the variance in CF suggesting that other variables which were not formally assessed in this sample (e.g., anxiety, etc.) may also play a predictive role. Follow-up studies should evaluate how results may differ with a larger sample size.

Figure: Four models predicting cognitive fatigue

Chronic fatigue is the aftermath of living, if you hadn’t experienced it you haven’t really lived your live. The tumultuous life we now lead and the demands we regularly place on ourselves, however, leads to a more unique form of fatigue – that of cognitive fatigue. Cognitive fatigue can last from anywhere between a few hours to several days and affects your ability to think. It negatively impacts on you overall quality of life. The clinical definition of cognitive fatigue is “a decrease, or inability to sustain, task performance throughout the duration of a sustained attention task”.

Berard et al investigated factors that may influence cognitive fatigue in MS. Specifically, they have studied the interrelatedness of fatigue, depression, sleep disturbances, and cognitive fatigue in MS. They used the Paced Auditory Serial Addition Test (PASAT) to quantify cognitive fatigue. Those who participated should have not had an underlying psychiatric condition, learning disability, seizures or head injury. Subsequently, they used modelling to study the interrelatedness (see above).

They found that model 4 was the best fit for the data collected when compared to the other competing models i.e. that cognitive fatigue is not only the result of sleep disturbance but also depression. This is not surprising as depression leads to reduced motivation and impacts on task performance. However, sleep quality turned out to be the most significant predictor of cognitive fatigue. Surprisingly, they did not find any correlation between disease severity and any of the other variables in each model, which may have been due to the small sample size.

This study is a good starting point for future studies of this ilk. It goes without saying that these models can be used to study the impact of interventions purported to improve sleep quality and hence cognitive fatigue.

About the author

Neuro Doc Gnanapavan


  • I have cognitive fatigue my sleep patterns are very bad as I can be up all night and awake all day this last for 2,3days and can go on for weeks I am going through the process off being told I have not got ms for the second time I have all the simptons I am on lots of meds haveing relapsing/remitng? My mobility is very poor and suffering lots with pins needles in my feet haveing lots of pain in hands and feet had MRI scans all clear had LUP. All clear to don’t no what to do as seen 2 separate neurological and no ideas as to what’s wrong with me 🙁kdee

    • Disturbed sleep patterns seem to be an important factor in this study. We have posted on sleep previously and the resource can be reviewed by inserting sleep into the search menu.

      Good luck with your neurology reviews.

  • Respectfully, I would like to suggest that the issue of Cognitive fatigue, while partially addressed by your four models, misses an important component. That is, you have sidestepped the underlying Chronic fatigue PwMS experience, which I don’t believe results directly from lifestyle, depression, sleep quality or even disease severity (LDSD). Indeed, the causation may be reversed, in that chronic fatigue is the cause of LDSD impairment, not the result. There is some organic element or process which produces this profound fatigue so unlike what people without MS experience. It is a profoundly disabling, misnamed symptom. I also suggest that the category of disease severity confuses the issue. One can, for example, be ambulatory, have sound sleep patterns, good cognitive function, and still be profoundly disabled just from this misnamed chronic fatigue. I have yet to see an adequate explanation for the cause and manifestation of chronic fatigue in MS patients. I don’t know, for example, what role mitochondrial function or other factors play. But I look forward to finding out.

    • Release of inflammatory cytokines by lymphocytes can cause fatigue. It's part of the fever response and reducing lesion activity seems to alleviate this, particularly with Tysabri, according to all the pwMS I've spoken to. Why Tysabri seems to be particularly effective here is yet to be revealed.

  • There are studies linking motor fatigue with cognitive fatigue. That seems to be a very different process, not linked to sleep quality or depression. For instance, walking to the point of near collapse. You are trying to explain how tired you are and are having problems finding words, etc. What causes that?



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