Cognitive trajectories in multiple sclerosis: a long-term follow-up study

Background: Cognitive impairment occurs in multiple sclerosis (MS) and undergoes a progressive worsening over disease course. However, clinicians still struggle to predict the course of cognitive function. To evaluate baseline clinical and imaging predictors of cognitive abilities worsening over time, we performed a latent trajectory analysis for cognitive performances in MS patients, up to 15 years from disease onset. Methods: We collected age, sex, education, dominant and non-dominant 9-hole peg test (9HP) and timed 25-foot walk (T25-FW) as well as MRI measures (grey matter volume and lesion load) within 6 months from disease diagnosis for relapsing–remitting MS (RR-MS) patients. At diagnosis and over the follow-up, we also assessed cognitive status through the symbol digit modalities test (SDMT). Cognitive impairment was defined by applying age-, gender- and education-adjusted normative values. Group-based trajectory analysis was performed to determine trajectories, and the predictive value of clinical and imaging variables at baseline was assessed through multinomial logistic regression. Results: We included 148 RR-MS (98 females and 50 males). Over 11 ± 4 year follow-up, 51.4% remained cognitively stable whereas 48.6% cognitively worsened. Cognitively worsening patients had a higher T25FW time (p = 0.004) and a reduced hippocampal volume at baseline (p = 0.04). Conclusion: Physical disability as well as hippocampal atrophy might depict patients at risk of cognitive worsening over the disease course. Therefore, using such predictors, clinicians may select patients to carefully evaluate for cognitive impairment as to eventually introduce cognitive rehabilitation treatments.