Pain and cognition in multiple sclerosis: distinct associations with objective and perceived impairment

Pain and cognitive impairment are common, disabling features of multiple sclerosis (MS), yet their relationship remains poorly understood. In particular, it is unclear whether pain is associated with objective cognitive performance or primarily influences patients' perceptions of their cognitive difficulties.

To examine the associations between pain, objective cognitive performance, and perceived cognitive impairment in people with MS (pwMS).

A retrospective cross-sectional analysis was conducted using data from 396 consecutive adult outpatients with confirmed MS and cognitive concerns referred for assessment to an MS neuropsychiatry service between April 2025 and April 2026. Objective cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS). Pain was measured using the Short-Form McGill Pain Questionnaire, mood using the Hospital Anxiety and Depression Scale, fatigue using the Fatigue Severity Scale, and perceived cognitive impairment using the Perceived Deficits Questionnaire. Pearson correlations and multivariable regression analyses were performed.

Pain showed small but significant bivariate associations with selected cognitive measures; however, pain did not independently predict objective cognitive performance after adjustment for demographic, clinical, and symptom-related variables. In contrast, perceived cognitive impairment was significantly associated with sensory pain, anxiety, depression, and fatigue, with the model explaining 44% of the variance.

Pain does not independently predict performance on objective cognitive tests in pwMS. In contrast, sensory pain contributes to perceived cognitive impairment alongside mood and fatigue. These findings highlight a dissociation between objective and subjective cognition in MS and underscore the importance of considering symptom burden when evaluating cognitive concerns.