The association of fatigue and pain with cognitive test performance in patients with [ME/CFS], 2025, Oosterman et al

[forestglip]

The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Joukje M. Oosterman, Marieke van der Schaaf, Willemien P.E. de Kleijn, Tanja A. Kuut, Inti A. Brazil, Hans Knoop

Highlights
• Fatigue severity was the strongest predictor of cognitive test performance.
• Pain severity and physical functioning predicted performance independently.
• With increasing age the negative relation between pain and performance is stronger.

Objectives
Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) typically perform worse on cognitive tasks. The present study explored the independent associations of fatigue and pain symptoms with cognitive performance in a large sample of patients who met CDC criteria of CFS (n = 1375), of whom most also met NICE/ IOM criteria (n = 1072). Moreover, we tested the hypothesis that these associations become stronger with older age and longer symptom duration.

Methods
Questionnaires and diaries were employed assessing fatigue and pain severity, together with the impact of health problems on daily life (using the SF-36 ‘Physical Functioning’ and ‘Bodily Pain’ subscales). Cognitive outcomes consisted of speeded performance measures, namely the Symbol Digit Test, motor speed, simple and choice reaction time (RT), and response inhibition. Categorical regression with lasso penalization was employed to identify relevant correlates of cognitive performance.

Results
Fatigue severity remained as only correlate of response inhibition. For the other cognitive outcomes, fatigue severity consistently emerged together with contributions of pain severity, bodily pain and/or physical functioning. Restricting these analyses to those patients meeting NICE/IOM criteria revealed overall similar results. Age, not symptom duration, moderated several relationships, showing more pronounced associations between cognitive performance and pain severity, physical functioning, and bodily pain with increasing age.

Conclusions
This study highlights that a multidimensional nature of symptoms, including fatigue and pain severity, and the impact on daily-life functioning, relate to lower cognitive performance in patients with ME/CFS. Studies are needed to identify the direction and potential causality of these associations.

Web | PDF | Journal of Psychosomatic Research | Open Access

 

[Andy]

From the 1375 included patients meeting CDC criteria of CFS, 1027 also met the NICE/IOM criteria.

To my skim read, for a paper with Knoop's name, this actually seemed reasonably written, with no glaringly obvious leaps to patient blaming.

 

[Utsikt]

The discussions of the results seems quite speculative and I’m not sure the simplistic models they mention add anything to the paper.

From personal experience, I have no doubt that both fatigue and pain can affect cognitive performance. But having had a lot of experience with both fatigue and pain before I got ME/CFS, it’s crystal clear that my current cognitive problems have little in common with those I experienced when in pain or fatigued pre-ME/CFS.

 

[Verity]

From personal experience, I have no doubt that both fatigue and pain can affect cognitive performance. But having had a lot of experience with both fatigue and pain before I got ME/CFS, it’s crystal clear that my current cognitive problems have little in common with those I experienced when in pain or fatigued pre-ME/CFS.

Agreed. I have fatigue, pain, and cognitive problems, and the latter is pretty clearly not caused by the former two. They probably generally track with each other in terms of severity. I appreciate that the authors didn’t assume causality.

 

[Utsikt]

I appreciate that the authors didn’t assume causality.

Absolutely, and they kept the door open for all possibilities.

We’ll probably never get an answer to how it works unless we somehow get medications that only block pain and/or fatigue but doesn’t interfere with the rest of the diseases processes.

 

[rvallee]

This study highlights that a multidimensional nature of symptoms, including fatigue and pain severity, and the impact on daily-life functioning, relate to lower cognitive performance in patients with ME/CFS. Studies are needed to identify the direction and potential causality of these associations.

Actually, no such studies are needed because there is only one plausible direction, it's not just obvious but almost ostentatiously so. There is something a bit funny with talking about "multidimensional" and then listing the two most common symptoms in all of medicine. All this talk of "dimensions" here is just cringe pseudoscience. They keep trying to turn a hard-but-difficult concept into a easy-but-complex one.

Fatigue severity was the strongest predictor of cognitive test performance.

Total mystery what direction this could be. But we know what they want it to be:

Further research is needed to explore the direction and nature of these relationships, exploring a potential bidirectional relationship between fatigue, pain and cognition

The traditional implausible one they've always been extremely biased in favor of, to the point of having asserted it for decade as fact, with extensive record of them saying this is what they've been using clinically for years. I can't even make sense of how such bidirectional relationship can even make sense.

This is just a button-pressing test. I have no idea what purpose they think it has. It's nothing they know about, for sure, but anyone who actually pays attention here will not be learning anything new. These people are flailing and wailing like one of those wacky waving inflatable tube guy.