Subjective fatigue is not associated with cognitive impairment in multiple sclerosis: Cross-sectional and longitudinal analysis

Background: Studies in multiple sclerosis (MS) report conflicting conclusions regarding fatigue and cognition, which may partly be due to the use of small sample sizes and frequent reliance on a cross-sectional approach. Objective: The ability to distinguish between these two disabling symptoms is necessary in order to properly assess and treat MS patients. Methods: In a retrospective analysis, we assessed the correlation between fatigue and neuropsychological (NP) testing using a cross-sectional (n = 465) and longitudinal approach (n = 69). Cognition was measured using a comprehensive battery called the Minimal Assessment of Cognitive Function in MS (MACFIMS), and fatigue was measured with the Fatigue Severity Scale (FSS). FSS scores were categorized as normal (≤4.0), borderline fatigue (4 < FSS < 5.0), and fatigued (≥5.0). Repeat assessments (n = 69) were categorized as improved or worsened by a change in FSS of either 0.5 or 1.0. Results: MS patients had significantly higher FSS scores than normal controls (P < 0.001). No correlation was found between FSS and NP scores in either cross-sectional or longitudinal analyses. Fatigue was moderately correlated with depression, assessed using the Beck Depression Inventory Fast Screen (BDIFS) (r = 0.44, P < 0.001). Longitudinally, there was a medium correlation between change in FSS and BDIFS (r = 0.34, P = 0.001), but no significant differences on NP scores using either definition of change. Conclusion: We conclude that self-reported fatigue, while correlated with self-reported depression, is not significantly related to cognitive capacity in MS.