Brain reserve and cognitive reserve in multiple sclerosis: what you've got and how you use it.

OBJECTIVE We first tested the brain reserve (BR) hypothesis in multiple sclerosis (MS) by examining whether larger maximal lifetime brain volume (MLBV; determined by genetics) protects against disease-related cognitive impairment, and then investigated whether cognitive reserve (CR) gained through life experience (intellectually enriching leisure activities) protects against cognitive decline independently of MLBV (BR). METHODS Sixty-two patients with MS (41 relapsing-remitting MS, 21 secondary progressive MS) received MRIs to estimate BR (MLBV, estimated with intracranial volume [ICV]) and disease burden (T2 lesion load; atrophy of gray matter, white matter, thalamus, and hippocampus). Early-life cognitive leisure was measured as a source of CR. We assessed cognitive status with tasks of cognitive efficiency and memory. Hierarchical regressions were used to investigate whether higher BR (ICV) protects against cognitive impairment, and whether higher CR (leisure) independently protects against cognitive impairment over and above BR. RESULTS Cognitive status was positively associated with ICV (R(2) = 0.066, p = 0.017). An ICV × disease burden interaction (R(2) = 0.050, p = 0.030) revealed that larger ICV attenuated the impact of disease burden on cognition. Controlling for BR, higher education (R(2) = 0.047, p = 0.030) and leisure (R(2) = 0.090, p = 0.001) predicted better cognition. A leisure × disease burden interaction (R(2) = 0.037, p = 0.030) showed that leisure independently attenuated the impact of disease burden on cognition. Follow-up analyses revealed that BR protected against cognitive inefficiency, not memory deficits, whereas CR was more protective against memory deficits than cognitive inefficiency. CONCLUSION We provide evidence of BR in MS, and show that CR independently protects against disease-related cognitive decline over and above BR. Lifestyle choices protect against cognitive impairment independently of genetic factors outside of one's control.