Cognitive reserve predicts long-term cognitive trajectories in relapsing-remitting multiple sclerosis

Background: The effect of cognitive reserve (CR) on cognition in people with relapsing-remitting multiple sclerosis (pwRRMS) has been partially investigated.Objectives: We aimed to explore the long-term cognitive trajectories of pwRRMS based on their CR, measured using the Vocabulary Knowledge Test (VOC).Methods: 78 pwRRMS underwent a neuropsychological evaluation at baseline and after a mean follow-up of 6.5 years. We carried out several mixed-design ANCOVA to test the effect of CR on longitudinal cognitive trajectories, controlling for the effects of disability and depression. Regression analyses were performed to assess the clinical predictors of longitudinal cognitive variation.Results: At follow-up, we observed improvements in cognitive scores within pwRRMS with high CR and a decline within pwRRMS with low CR. VOC scores increased at follow-up evaluation in the whole sample, and this change was associated with the female sex. VOC emerged as the only predictor of cognitive changes over time.Conclusions: CR, estimated by VOC, can increase over time by engaging in intellectually enriching activities, and may predict long-term cognitive outcomes in pwRRMS. The identification of pwRRMS with low CR, and therefore, most at risk of future cognitive decline, should prompt the implementation of CR enhancement interventions to delay the onset of cognitive impairment.