Tired minds, normal scores: rethinking cognitive fatigue in multiple sclerosis, 2025, Davide Spinetti et al

[Mij]

Cognitive fatigue is among the most pervasive and disabling symptoms experienced by individuals with multiple sclerosis (MS), yet it remains underrecognized and undertreated in both research and clinical settings. Despite its prevalence, cognitive fatigue is often confused with general fatigue or overlooked in standard neuropsychological assessments that rely on brief, decontextualized performance measures. This perspective argues for a paradigmatic shift in how cognitive fatigue is conceptualized and managed.

This perspective define it as a core, dynamic dysfunction affecting the cognitive system’s capacity to sustain effort over time, distinct from both general and subjective fatigue. A growing body of evidence, highlighted in this article, shows a frequent dissociation between perceived fatigue and objective fatigability, underscoring a fundamental flaw in current assessment tools. The authors call for the integration of prolonged, dynamic, and ecologically valid measures, such as extended neuropsychological tasks and digital phenotyping, into clinical protocols.

We propose repositioning cognitive fatigue as a distinct clinical target, requiring its own specific strategies for identification, monitoring, and intervention. Reframing cognitive fatigue in this way offers a critical step toward more accurate diagnostics and truly individualized care, bridging the gap between clinical findings and the patient’s lived experience

LINK

 

[Mij]

Introduction​

Multiple sclerosis (MS) is well known for its motor symptoms, sensory disturbances, and visual impairments, but perhaps less visible, though no less disabling, are the cognitive consequences of the disease (1, 2). Among these, cognitive fatigue stands out as both extremely common and poorly understood. Studies suggest that between 65 and 90% of individuals with MS report experiencing some form of fatigue, and a significant portion of them identify cognitive fatigue as the most debilitating aspect (3–5). Despite its prevalence and profound impact on quality of life, cognitive fatigue remains underrepresented in diagnostic frameworks and therapeutic approaches. A core challenge in addressing this symptom is its elusive nature and a lack of consistent terminology. For the purpose of this Perspective, we define “Fatigue” as a broad, overarching term for a state of weariness that can be physical, mental, or a combination of both (6) (see glossary). Within this, we distinguish between:

• Subjective cognitive fatigue: the patient’s self-reported, internal sensation of mental exhaustion or lack of energy for an ongoing cognitive task (

• Objective cognitive fatigability: a measurable decline in cognitive performance (e.g., speed, accuracy) over the duration of a sustained or repeated task

The distinction between the subjective feeling and the objective, measurable decline is crucial, as a growing body of evidence shows these two dimensions are often dissociated, with weak or no correlation between them (10, 11). This paradox highlights a fundamental failing of current assessment paradigms, which are primarily based on brief, decontextualized performance measures.

Standard neuropsychological tests, while effective at identifying stable deficits, often fail to capture the dynamic and context-sensitive nature of cognitive fatigability, and neuropsychological tests alone may fail to provide clinical predictability (42). As a result, a patient may perform “within normal limits” on a standard cognitive battery yet struggle to maintain attention at work or follow a conversation for a prolonged period (12).

This mismatch between clinical findings and lived experience underscores the urgent need for a new conceptual and methodological approach. This article argues for a paradigmatic shift in how cognitive fatigue in MS is conceptualized and managed. Rather than treating it as a vague, secondary complaint, the Authors propose to reposition it as a core, dynamic dysfunction that requires specific assessment tools, dedicated interventions, and centrality in clinical decision-making.

This perspective aims to illuminate why current models fail, what a more ecologically valid approach would look like, and how shifting our clinical priorities might transform care for people with MS.

 

[Hutan]

From the excerpts posted, this looks like a useful contribution to the field of cognitive fatigue. Rather than dismissing the feeling of fatigue as some moral failing in the person reporting it when tests fail to provide objective evidence of a problem, these authors seem to be saying 'the problem is in our tests. Let's make better ones.'

Among these, cognitive fatigue stands out as both extremely common and poorly understood. Studies suggest that between 65 and 90% of individuals with MS report experiencing some form of fatigue, and a significant portion of them identify cognitive fatigue as the most debilitating aspect (3–5).

It's also good to see the recognition of cognitive fatigue as a life-limiting problem worthy of study and treatments.

This paper might be useful in advocacy efforts e.g. if a patient reports cognitive constraints in order to qualify for assistance/benefits, but the tests don't support the claim.

It also reminds me of how much in common people with MS have with people with ME/CFS. My experience so far has been that MS doctors don't want to have anything to do with ME/CFS. But, if there was willingness, I think MS clinical services would have useful things to offer people with ME/CFS.

 

[Hoopoe]

Cognitive fatigue, as distinct from physical fatigue, refers to the gradual decline in cognitive efficiency and mental energy during sustained mental activity (7, 8). One of the most frustrating experiences reported by people with MS is the mismatch between how they feel and how they are clinically assessed (43). It is not merely a subjective complaint of tiredness, nor is it fully captured by momentary lapses in attention or performance scores. Rather, it reflects a more fundamental limitation in the brain’s ability to maintain cognitive performance over time.

That describes my cognitive fatigue as well. The "over time" part is important... the limitations become apparent as I exert myself, and once the brain is exhausted, it does not recover as quickly and easily as a normal.

 

[Liie]

That describes my cognitive fatigue as well. The "over time" part is important... the limitations become apparent as I exert myself, and once the brain is exhausted, it does not recover as quickly and easily as a normal.

Same.

 

[Utsikt]

It also reminds me of how much in common people with MS have with people with ME/CFS. My experience so far has been that MS doctors don't want to have anything to do with ME/CFS. But, if there was willingness, I think MS clinical services would have useful things to offer people with ME/CFS.

I have family with MS. They immediately understood my brainfog and the crashes long before I knew about PEM or understood.

 

[Mij]

I only saw and posted this paper after I had my phone assessment appointment with my GP yesterday. Please move this to appropriate thread if necessary.

The section on the form regarding "impairment of mental functions necessary for daily life" was the most difficult to describe. It required a explanation, we can not just check off a "yes" or "no" answer:

1). Adaptive Functioning: From the list they provided, "Adapt to change" was a big 'no' for me. I explained to her that everything I do is preplanned, calculated, and that I have a short energy battery. I can not be spontaneous. If I'm presented with a situation that I haven't planned for then it is full stop brain and physical shut-down. Over exerting my cognitive energy also depletes my physical energy. I start to slur my words and sway when I walk. I need to immediately lie down to recover.

2). Concentration: Focus on simple task for any length of time. Absorb and retrieve information in short-term. We checked off "severe limitations" after I gave her a long explanation.

The other list of questions did not apply to me so we left it blank.

In the end she understood that "tiredness and fatigue" were not the best terms to use when describing ME/CFS.

 

[rvallee]

Looks pretty good, although this is stuff millions of people have been saying for decades, and it's frankly ridiculously obvious.

Objective tests are only useful if what they measure is related to the problem. No such tests exist for cognitive dysfunction like this, hence they are useless. But instead of applying scientific reason, it's been favored instead to argue that the tests are flawless, it's the patients who are wrong about their complaints.

Could have saved decades of wasted nonsense if they had simply listened to things a child can easily reason through.

It's a common joke/meme/trope on Internet forums for people to try to poke holes in studies, pointing out obvious flaws, usually met with replies like "geez, did the smart people with advanced degrees think about 'super obvious thing'? you think?", and usually they do, but in medical research not involving biology, they generally don't.

Which is normal when the problem is subjective. They have to listen to what people are telling them to work through it, which, for a change, these researchers have managed. But most don't, having literally made up fake mental illnesses where our perception is the problem, because most of them literally can't imagine otherwise. So it's good to put it out there, but damnit this is truly the most inefficient way of solving problems besides "first, create a universe, then wait for intelligent life to figure it out".