Longitudinal investigation of neuroimaging changes related to memory decline in multiple sclerosis: Testing a mechanistic model.

Background: Memory decline is common in multiple sclerosis (MS), although pathophysiological mechanisms are not fully understood.

Objective: The objective was to investigate the relationship of changes in structural and functional neuroimaging markers to memory decline over 3-year follow-up.

Methods: Participants with MS underwent cognitive evaluation and structural, diffusion, and functional 3T magnetic resonance imaging (MRI) scans at baseline and 3-year follow-up. Changes in neuroimaging metrics from baseline to follow-up were compared between memory stable and memory decline groups. Our hypothesis that structural and functional connectivity changes mediate the association of atrophy to memory decline was tested.

Results: A total of 249 MS patients completed baseline visit; 169 (67.8%) returned at 3-year follow-up. Based on ⩾10% decline, memory decline was observed in 44.4% (n = 75). Those with memory decline showed marginally greater whole-brain volume loss over time compared with those with stable memory performance (p = 0.08). In those with memory decline, changes in white matter tract integrity were related to regional cortical thinning (p < 0.01). Exploratory mediation analysis revealed structural and functional connectivity to mediate the relationship of atrophy to verbal and visual memory decline.

Conclusion: Further work is needed to characterize complex interrelationships of atrophy and structural/functional connectivity changes to memory decline in MS.