Operationalising cognitive fatigability in multiple sclerosis: a Gordian knot that can be cut?

Background: Researchers have attempted to operationalise objective measures of cognitive fatigability in multiple sclerosis (MS) to overcome the perceived subjectivity of patient-reported outcomes of fatigue (PROs). Measures of cognitive fatigability examine decrements in performance during sustained neurocognitive tasks. Objective: This personal viewpoint briefly summarises available evidence for measures of cognitive fatigability in MS and considers their overall utility. Results: Studies suggest there may be a construct that is distinct from self-reported fatigue, reflecting a new potential intervention target. However, assessments vary and findings across and within measures are inconsistent. Few measures have been guided by a coherent theory, and those identified are likely to be influenced by other confounds, such as cognitive impairment caused more directly by disease processes, depression and assessment biases. Conclusion: Future research may benefit from (a) developing a guiding theory of cognitive fatigability, (b) examining ecological and construct validity of existing assessments and (c) exploring whether the more promising cognitive fatigability measures are correlated with impaired functioning after accounting for possible confounds. Given the issues raised, we caution that our purposes as researchers may be better served by continuing our search for a more objective cognitive fatigability construct that runs in parallel with improving, rather than devaluing, current PROs