Longitudinal MRI Study Reveals Mechanisms Associated with Cognitive Worsening in MS Patients

Cognitive impairment is a common and debilitating consequence of multiple sclerosis (MS), affecting approximately 40-65% of patients. However, the underlying mechanisms contributing to cognitive decline in MS remain poorly understood. A recent longitudinal multiparametric MRI study published in the Journal of Neurology aimed to shed light on these mechanisms by investigating changes in brain structure, function, and connectivity in MS patients over time.

The study included 35 MS patients and 22 healthy controls (HC) who underwent comprehensive 3 T brain functional and structural MRI scans at baseline and after a median follow-up of 3.4 years. Cognitive assessment was performed using Rao’s battery, and reliable change index scores were used to identify cognitive worsening. The researchers explored associations between cognitive decline and longitudinal changes in regional T2-hyperintense white matter (WM) lesions, diffusion tensor microstructural WM damage, gray matter (GM) atrophy, and resting-state (RS) functional connectivity (FC).

The HC cohort did not exhibit significant changes in brain structure or functional connectivity. However, 29% of MS patients (10 individuals) demonstrated cognitive worsening. Comparing cognitively worsened MS patients to cognitively stable ones revealed more severe GM atrophy in the right anterior cingulate cortex and bilateral supplementary motor area (P < 0.001). Additionally, cognitively worsened MS patients exhibited decreased RS FC in the right hippocampus of the right working memory network and in the right insula of the default mode network. Conversely, increased RS FC was observed in the left insula of the executive control network in the cognitively stable group compared to the worsened group (P < 0.001). Importantly, no significant accumulation of focal WM lesions or microstructural WM abnormalities occurred in either patient group.

“GM atrophy progression in cognitively relevant brain regions combined with functional impoverishment in networks involved in cognitive functions may represent the substrates underlying cognitive worsening in MS,” the authors of the study wrote.

These findings have potential implications for the development of targeted interventions to mitigate cognitive impairment in MS. By identifying the specific brain regions and networks involved in cognitive decline, future research may focus on therapies that target these areas to preserve cognitive function in MS patients.