Sex differences in brain resilience of individuals with multiple sclerosis

Background: Brain resilience allows maintenance of neurocognitive function in the face of age or disease -related neural changes. Objective: Test the hypothesis that women and men with MS differ in brain resilience. Methods: This cross-sectional analysis of prospective cohort data included 11,297 patients. Linear mixed effects models predicted performance outcomes on tasks of fine motor dexterity and cognitive processing speed for MRI proxies of disease burden: brain parenchymal fraction (BPF), T2 lesion volume, volumes of deep gray, thalamus, white and cortical gray matter. Covariates were age, sex, age -by -sex, current disease -modifying therapy, disease phenotype, education, total brain volume, and total brain volume -by -sex. Sex-by-MRI metric terms tested primary hypothesis of differential brain -behavior relationships between men and women. Results: Final sample included 10,286 participants. Lower BPF was associated with worse performance (p 's <0.001) in men and women; association was smaller for women than men for processing speed ( beta eta (Women-Men) = - 0.044, 95 % CI=[ -0.087, -0.002], p = 0.041) and manual dexterity ( beta eta( Women-Men )=-0.073, 95 % CI=[ -0.124, -0.023], p = 0.005). For each MRI variable, women demonstrated better neurocognitive function controlling for disease burden. Discussion: Sex differences in brain metric-neurofunctional performance relationships of people with MS suggest women have higher resilience than men in the face of increased disease burden. Future work exploring mechanism is warranted.