Protective effects of cognitive and brain reserve in multiple sclerosis: Differential roles on social cognition and 'classic cognition'

Background: According to cognitive reserve (CR) and brain reserve (BR) theories, lifetime intellectual enrichment and maximal brain volume protect against cognitive decline. Objective: To examine the effects of CR and BR on social cognition in multiple sclerosis (MS), and compare it with 'classic cognition'. Methods: We included 60 MS patients and 60 healthy controls matched on age, sex, and education. Education was used has a proxy of CR and intracranial volume (ICV) as a proxy of BR. Participants underwent Theory of Mind (ToM) testing (Eyes Test, Videos Test), comprehensive neuropsychological assessment and 3Tesla brain MRI. Cortical and subcortical grey matter (GM) volumes were calculated. Results: We found positive effects of education and ICV on general cognitive status and ToM performance, respectively. Higher education moderated the impact of subcortical GM atrophy on 'classic' cognitive status (R2=0.219, p=<0.001). Conversely, greater ICV attenuated the impact of cortical GM atrophy on Eyes Test (R2=0.158, p=0.002) and Videos Test (R2=0.198, p=0.001). Stratification for disease duration showed that the protective effect of education/ICV occurred in early stages of disease (<10 years). Conclusion: CR and BR have differential protective roles in MS, with BR having a positive effect on social cognition and CR on 'classic' cognitive domains.