Mild cognitive impairment impacts association of functional brain connectivity with cognition in older adults with and without multiple sclerosis.

Cognitive decline is common in multiple sclerosis (MS), although neural mechanisms are not fully understood. The objective was to investigate the impact of mild cognitive impairment (MCI) on the relationship between resting state functional connectivity (RSFC) and cognitive function in older adults with multiple sclerosis (OAMS) and age matched healthy controls. Participants underwent magnetic resonance imaging (MRI) scans and cognitive assessments. The Oral Symbol Digit Modalities Test (SDMT) was the outcome measure. Multiple linear regressions examined the relationship between RSFC networks and SDMT performance across the cohort and within group-specific analyses. These analyses were repeated with MCI as a moderator. Adjusted analyses showed that better SDMT performance correlated significantly with higher RSFC in sensorimotor (p = 0.01), left frontoparietal (p = 0.027), and salience (p = 0.047) networks. Stratified analyses showed significant positive associations for the OAMS group in medial visual (p = 0.007) and sensorimotor (p = 0.018) networks. Among OAMS, MCI moderated the association between RSFC and SDMT performance in the posterior default mode (p = 0.016) and subcortical (p = 0.042) networks, while no significant moderation effects were observed for the control group. Higher RSFC in brain networks correlates with better cognition in aging, but this relationship is modified in the presence of MS and MCI.