Cortisol levels are increased in patients with multiple sclerosis (MS) compared with healthy controls, with slightly higher levels among those with MS without than those with cognitive fatigue, according to study results published in Multiple Sclerosis and Related Disorders.

Previous studies have shown that cortisol levels are increased in patients with MS, but limited data exist regarding the association between cortisol levels, cognitive fatigue, and load. The objective of the current study was to determine the association between cognitive fatigue and salivary cortisol in patients with MS and healthy controls.

Study researchers determined participants’ salivary cortisol levels in the morning and afternoon, before and after 5 runs of a cognitively demanding divided attention task. After doing a practice run to ensure they understood the task, participants completed 5 blocks of 100 trials each. Study researchers then assessed the median reaction time for correct trials and the number of misses of targets (omissions) for the first and last block.

The study included 27 (mean age, 50.2 years; 65.5% women) patients with MS and cognitive fatigue and 13 (mean age, 56.8 years; 72.7% women) patients with MS without cognitive fatigue. Additionally, 20 (mean age, 46.4 years; 50% women) healthy controls were included in the study sample.

There were no differences between participants with MS with and without cognitive fatigue regarding age, gender, or disability. However, depressive moods and levels of fatigue were higher among those with cognitive fatigue.

Compared with healthy controls, all participants with MS had significantly higher cortisol levels at the first measurement of the morning and of the afternoon. Circadian cortisol levels at the first measurement of the morning and the first measurement of the afternoon were significantly higher in patients with MS without cognitive fatigue compared with healthy controls. As anticipated, cortisol levels changed throughout the day for all groups, but the change was significantly larger among those with MS without cognitive fatigue, compared with all other groups.

Omissions during the cognitive task in the morning and in the afternoon were significantly more common among patients with MS without cognitive fatigue, compared with healthy controls. The researchers noted that in patients with MS without cognitive fatigue, the cortisol level dropped significantly during the morning session, while the number of omissions remained high. However, in healthy controls and in those with MS and cognitive fatigue, cortisol levels decreased between the morning and the afternoon sessions, but the number of omission remained stable.

The study had several limitations, including the small sample size, inability to access the cortisol awakening response directly, and lack of data on attention task related anxiety and inflammatory markers.

“MS-NF [MS without cognitive fatigue] patients, and not MS-F [MS with cognitive fatigue] patients, deviate in cortisol release and task performance from healthy controls and from MS-F patients. We suggest that MS-NF patients suffer from a dysregulation of their circadian cortisol level,” concluded the study researchers.


Hildebrandt H, Stachowiak R, Heber I, Schlake HP, Eling P. Relation between cognitive fatigue and circadian or stress related cortisol levels in MS patients. Mult Scler Relat Disord. 2020;45:102440. doi:10.1016/j.msard.2020.102440 

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