Cognitive Progression Independent of Relapse and MRI Activity in Multiple Sclerosis

Abstract

Objectives Progression independent of relapse activity (PIRA) and MRI activity (PIRMA) have been demonstrated in multiple sclerosis (MS). A recent study evaluated cognitive PIRA, but MRI was not considered. We aimed to determine whether cognitive PIRA results differ when MRI activity is included. Methods From the Verona MS cohort, we selected a group of patients with relapsing-remitting MS (RRMS) clinically/MRI routinely followed over time who underwent multiple neuro-psychological assessments over 4 years on average. For this project, we focused on the Symbol Digit Modalities Test as the cognitive outcome. Significant cognitive decline events were determined to be temporally correlated with/independent of acute disease activity (relapses or MRI), using a conservative approach (9 months before/after the cognitive decline). Results A total of 301 patients with RRMS were included (mean ± age = 39.5 ± 11.3 years, 73.8% female). Fifty patients (16.6%) showed significant cognitive decline. Among those with con-firmatory MRI/clinical evaluation after decline (n = 46), only 9 patients (19.6%) showed evidence of any acute disease activity, while most (n = 37, 80.4%) had cognitive decline independent of both relapse and MRI activity (cognitive PIRMA), mostly independent of Expanded Disability Status Scale worsening (78.4%). Discussion The existence of cognitive PIRMA has been preliminarily demonstrated. It affects most cog-nitively declined patients with RRMS and should be carefully considered. Future confirmatory prospective studies are needed.