COGNITIVE decline in relapsing-remitting multiple sclerosis (RRMS) can progress independently of both relapses and MRI-detected disease activity, challenging traditional methods of monitoring MS progression, according to the results of a new study. Researchers analyzed data from 301 RRMS patients in the Verona MS cohort, focusing on the Symbol Digit Modalities Test as a measure of cognitive function. Over an average follow-up of four years, 16.6% of patients exhibited significant cognitive decline.
Among the 46 patients with available follow-up MRI or clinical evaluations after cognitive decline, only 19.6% showed evidence of acute disease activity, such as relapses or new MRI lesions. The majority (80.4%) experienced cognitive decline independent of these markers—a phenomenon termed cognitive PIRMA (Progression Independent of Relapse and MRI Activity). Additionally, 78.4% of these cases progressed without a corresponding increase in physical disability as measured by the Expanded Disability Status Scale.
These findings underscore the importance of comprehensive neuropsychological monitoring in MS care. Current clinical evaluations often rely on relapse history and MRI findings to assess disease progression, but this study suggests that cognitive impairment may develop silently, without detectable inflammatory activity. As cognitive dysfunction significantly impacts quality of life and daily functioning, incorporating routine cognitive testing into MS management could enable earlier intervention and better long-term outcomes.
While these results are compelling, researchers emphasize the need for prospective studies to confirm cognitive PIRMA and explore its underlying mechanisms. Future work could help refine MS treatment strategies to address cognitive decline before it significantly affects patients’ lives.
Reference: Ziccardi et al. Cognitive Progression Independent of Relapse and MRI Activity in Multiple Sclerosis. Neurol OA. 2025;1(1). doi:10.1212/WN9.0000000000000005.
Anaya Malik | AMJ
