Cognitive reserve and neuropsychological performance in multiple sclerosis: A meta-analysis

Objective: Cognitive dysfunction is frequent in multiple sclerosis (MS), and its relationship with cognitive reserve (CR) has been investigated in several studies with conflicting results. In this meta-analysis, we here sought to determine the relationship between CR and cognition in MS patients and to ascertain whether demographic or clinical variables could moderate the above-mentioned relationship. Method: We searched three electronic databases for studies assessing the relationship between CR and performance in 6 cognitive domains or processes (verbal and spatial memory, attention, processing speed, verbal fluency, inhibitory control). The initial literature search yielded 1,452 articles; 245 full-texts were evaluated, and 18 studies were entered into the meta-analysis. Mean weighted effect sizes (ES) were calculated using Hedges' g. Sensitivity analyses and examinations of funnel plots served to reduce heterogeneity. Results: A total number of 1,903 MS patients were included, analyzing each aspect of cognition separately. ES for the relationship between CR and cognition were significant (except for verbal fluency) and moderate. After applying specific techniques to reduce heterogeneity, the verbal fluency ES became significant. Metaregression analysis revealed that older age and female sex increased the ES for attention and verbal memory outcomes. Conclusions: High levels of CR were associated with better cognitive task performance in verbal and spatial memory, attention, processing speed, verbal fluency, and inhibitory control. The results indirectly emphasize the value of early cognitive assessments of cognitive status and CR levels to enable timely initiation of cognitive interventions to increase CR in MS in patients with low levels of CR.