Subjective mental fatigue mediates the relationship between information processing speed and verbal memory deficits in multiple sclerosis.

Subjective mental fatigue (MF) and cognitive dysfunction significantly impair the quality of life in people with multiple sclerosis (PwMS), particularly impacting information processing speed (IPS) and verbal learning-memory (VL/M). We assessed 66 PwMS and 38 healthy controls (HC) via the oral form of the symbol digit modalities test (SDMT-Of) for IPS, the Greek verbal learning test (GVLT) for VL/M, and the cognitive subscale of the modified fatigue impact scale (MFIS-c) for MF. This aimed at investigating the mediating role of MF in the relationship between IPS and VL/M in PwMS. PwMS performed significantly worse than HC across all domains. Mediation analysis, controlling for age, sex, education, disease duration, and MS-type, revealed a significant effect of IPS on VL/M in PwMS. This effect became non-significant once MF was introduced, whereas the indirect effect of IPS on VL/M through MF remained significant. No significant mediation effects were observed in HC, even after controlling for age, sex, and education, underscoring the unique impact of MF on MS. This study highlights the mediating role of subjective MF in cognitive deficits among PwMS, suggesting that interventions targeting MF could enhance cognitive performance.Trial registration: The study is registered with ClinicalTrials.gov Identifier NCT04806568 ( https://www.clinicaltrials.gov/study/NCT04806568 ).