Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

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Research has identified the neural response to errors (the error-related negativity; ERN) as a marker of current anxiety, as well as risk for future anxiety. Previous work found that traditional cognitive behavioral therapy approaches do not impact the ERN. However, none of these approaches directly target the psychological constructs linked to an increased ERN (e.g., error sensitivity). In the current study, we examine the extent to which a brief, computerized intervention ("Treating the ERN"; i.e., TERN) might impact the ERN by reducing error sensitivity. Results suggest that TERN reduced the ERN and that the impact of the intervention was larger amongst individuals with an increased baseline ERN. This study is an important first step in the development of a novel intervention approach that directly targets error sensitivity, and thereby the ERN.

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Background Cognitive impairment affects many patients with multiple sclerosis (MS). NeuroTrax, a computerized cognitive screen that can be administered during routine clinical care, provides a consistent, validated, objective cognitive profile measure with a global cognitive score (GCS) and seven individual domain scores. Natalizumab is an efficacious therapy for relapsing MS, demonstrating reductions in disability worsening and MS disease activity measured by magnetic resonance imaging. Objective The aim of this study was to assess cognitive function as measured by NeuroTrax in MS patients treated with natalizumab for ≥ 2 years. Methods This retrospective observational study included adult MS patients in the United States who received 300 mg intravenous natalizumab every 4 weeks for ≥ 2 years. NeuroTrax data were evaluated at baseline and yearly thereafter. Changes in GCS and the seven individual cognitive domain scores from baseline to after 24 infusions of natalizumab were analyzed. Results In the study population at baseline (N = 52), 22 patients (42.3%) had disease duration of 0-5 years; 12 patients (23.1%) were treatment naive. GCS score improved significantly from baseline [mean 95.5, standard deviation (SD) 12.9] to year 2 (mean 98.9, SD 13.2; change from baseline 3.4; p = 0.003). After 2 years on natalizumab, 17 patients (32.7%) demonstrated clinically significant improvement (increase from baseline > 1 SD) in GCS. Results were similar regardless of whether patients had previously received MS therapy. Conclusions Patients treated with natalizumab demonstrated significant improvement in cognitive function, measured by NeuroTrax GCS, over 2 years of treatment. Key PointsNatalizumab significantly improved NeuroTrax global cognitive score over 2 years of treatment, regardless of whether patients were treatment-naive or were previously treated with other disease-modifying therapies.Numerical improvements were observed for all seven individual cognitive domains from baseline to 2 years.These results indicate that some aspects of cognitive impairment can be reduced in patients with multiple sclerosis treated with natalizumab.