Cognitive reserve in multiple sclerosis: The role of depression and fatigue.

Background: Several reports suggest that cognitive reserve (CR) may protect against cognitive impairment in MS. Fatigue and depression are common in MS. Yet, their influence on engagement with activities that build CR is unclear.

Objectives: This study aimed to achieve a better understanding of CR-building in MS, by examining how CR differs in people with MS (pwMS) compared with neurologically healthy individuals and by investigating how common MS symptoms interact with CR-building.

Methods: In total, 206 pwMS and 150 age- and gender-matched controls participated in this cross-sectional study. Participants completed self-report measures of CR accumulated in early life and across the lifespan (including education, occupation, cognitively enriching leisure activities), and of cognitive functioning, fatigue, depression, anxiety and MS-impact on everyday life.

Results: PwMS' recent engagement in cognitively enriching leisure activities was negatively associated with self-reported cognitive difficulties (rho = -0.31, p < 0.001). However, after controlling for fatigue and depression, this association was no longer present. Correspondingly, we observed that higher levels of depression were associated with lower engagement in cognitively enriching leisure activities (B = -0.41 (95% confidence interval (CI): -0.61 to -0.22), p < 0.001).

Conclusion: Our results highlight the importance of addressing depression and fatigue in the context of lifestyle recommendations.