Advancing Age Modulates Associations Between Cognitive Impairment and Brain Volumes in Early MS

INTRODUCTION: Cognitive impairment is common in multiple sclerosis (MS), but manifestations following the first demyelinating event are relatively unexplored. We investigated cross-sectional associations between magnetic resonance imaging (MRI)-derived brain volumes and the presence of cognitive impairment outcomes five years after the first presentation with a demyelinating event. METHODS: Comprehensive cognitive assessments were performed five years after a first clinical demyelinating presentation using the Minimal Assessment of Cognitive Function in MS (MACFIMS). Participant Z scores were calculated for each MACFIMS subtest using available regression-based normative data. Participants were defined as having a cognitive outcome if one or more MACFIMS subtests were below the applied cutoff of Z ≤ -1.50. Gray matter volumes (GMV) were calculated using 3D T1-weighted MRI sequences. Logistic regression models assessed associations between 5-year MRI measures and cognitive impairment (adjusting for total intracranial volume where relevant). RESULTS: Forty participants were recruited. Lower GMV at 5 years was associated with 5-year cognitive impairment outcomes (OR = 1.06 per 1 cm³ decrease in GMV, 95% CI [1.00-1.13], p = 0.044). Among participants with a cognitive impairment outcome, there were significant associations between lower GMV and advancing age (p = 0.0095). Exploratory analysis of estimated marginal contrasts suggested that cognitive impairment outcomes were potentially associated with GMV above the age of 39 years (Z ≤ -1.50: p = 0.0476). DISCUSSION: Five years after a first demyelinating event, GMV volumes on MRI are significantly associated with the presence of cognitive outcomes, while advancing age also appears to be associated with GMV and cognitive outcomes.