To systematically review longitudinal studies examining the relationship between MRI changes and cognitive changes in people with multiple sclerosis (MS) over ≥1 year follow-up.

An extensive and methodical search of online databases was conducted to identify qualified studies until August 2023. Among various cognitive tests and magnetic resonance imaging (MRI) measures, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), verbal fluency, T2 lesion volume (T2LV), white matter lesion volume (WML), and grey matter volume (GMV) qualified for inclusion in a meta-analysis investigating the association of cognitive changes to neuroradiological changes.

Thirty-five studies met inclusion criteria. Twenty studies (57%) examined SDMT/PASAT associations with MRI metrics, 11 (31%) focused on verbal learning/memory, 10 (29%) on visuospatial learning/memory, and 8 (23%) on verbal fluency. Five studies qualified for meta-analysis. Significant correlations were found between SDMT/PASAT and GMV (rs=0.67, 95% CI 0.44-0.91), and between verbal fluency and T2LV (rs=0.35, 95% CI 0.09-0.60).

Longitudinal cognitive decline in MS, particularly in SDMT/PASAT and verbal fluency, correlates significantly with grey matter atrophy and T2 lesion accumulation. However, findings are limited by heterogeneous methodologies, small sample sizes, and paucity of high-quality longitudinal studies. Future research should employ standardized cognitive batteries and advanced imaging techniques to better characterize brain-behavior relationships in MS progression.