Discrepancy between subjective and objective cognitive function in multiple sclerosis and association with mood, fatigue, and pain

Background Interpretation of cognitive impairment (CI) in persons with multiple sclerosis (PwMS) is limited by discrepancies between objective and subjective evaluation. Objectives Evaluate relationships between subjective and objective cognitive measures, accounting for contributors. Methods Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), patient-reported outcomes, Processing Speed Test (PST), Rey Auditory Verbal Learning (RAVLT), Visual Memory Test (VMT), Face Emotion Recognition (FER), Corsi, and Flanker test scores were collected. Spearman correlations, diagnostic metrics, and latent profile analysis assessed associations and cognitive phenotypes. Results In 83 PwMS, only 4.8–15.7% showed objective domain-specific CI, yet 42.2% reported significant CI. However, 51.8% had objective impairment in ≥1 domain. Compared with PwMS without objective or subjective CI, those with subjective but no objective CI had higher Hospital Anxiety Depression Scale-A (9.92 vs. 4.83) and D (8.23 vs. 2.88), and Fatigue Severity Scale (5.56 vs. 3.80) scores, p < 0.05. Latent profile analysis identified a performant cluster (C1, n = 36) and a less performant cluster (C2, n = 46) with higher mean z-scores on PST (0.46 vs. −0.70), VMT (0.32 vs. −0.54), RAVLT (0.99 vs. −0.06), and FER (0.57 vs. −0.80), p < 0.005, in C1. The MSNQ scores were similar between clusters. Conclusion A discrepancy between subjective and objective CI is observed. Subjective CI is associated with anxiety, depression, and fatigue. Multidomain testing and assessment of contributors may help reconcile this discrepancy.