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 (ßetaWomen-Men=-0.044, 95 % CI=[-0.087, -0.002], p = 0.041) and manual dexterity (ßetaWomen-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.

Disparities in DMT treatment: Demographic and neurocognitive differences between MS patients currently treated versus not treated with disease-modifying therapies.

BACKGROUND: Current treatment guidelines recommend consideration of disease-modifying therapy (DMT) for all multiple sclerosis (MS) patients, but barriers to access have begun to be identified. In particular, prior studies have found that people with higher education have better access to DMTs, perhaps explained by the association of higher education with higher income. And while the majority of people with MS are women, being male is also associated with higher income. These factors argue for the need to better understand whether there are differences in DMT uptake based on sex and education. Finally, in addition to well-documented benefits of DMTs for slowing disease progression, there is growing evidence to suggest benefits of DMTs for cognitive functioning. OBJECTIVE: Determine whether rates of DMT treatment differ based on education and sex. Secondarily, we investigate whether neurocognitive test performance differs in treated versus not treated groups. METHODS: In cross-sectional data, mixed effects linear regression evaluated differences in education and sex of those treated versus not treated with DMTs. Models included the following predictors: age, disease duration, MS subtype, sex/education, disability, atrophy, and T2 lesion volume. Propensity score weights were extracted to obtain unbiased estimates of the relationship between DMT status and each outcome of interest. The same models evaluated performance differences between groups on an iPad-based processing speed test (PST) and manual dexterity test (MDT). RESULTS: Controlling for covariates, individuals with less education (OR=1.09, 95 % CI=[1.03, 1.14], p = 0.003) and women (OR=0.80, 95 % CI=[0.72, 0.90], p < 0.001) were less likely to be currently treated with DMTs. Small effect size association was shown for DMT treatment with better performance on PST (beta=0.09, CI=[0.06, 0.13], p < 0.001) and MDT (beta=0.05, CI=[0.01,0.08], p = 0.011). CONCLUSIONS: Women and people with lower education had a lower likelihood of being currently treated with DMTs. After controlling for all relevant variables, an independent (small) association of DMT treatment to better performance on tests of processing speed and fine motor dexterity was found. Reasons for disparities remain to be investigated in future work, and may include employment status, health insurance coverage, or sex differences in risk tolerance.