Does cognitive reserve play any role in multiple sclerosis? A meta-analytic study

Background: Inconsistent evidence is available about the possibility that cognitive reserve (CR) moderates the impact of disease progression, evaluated by MRI biomarkers (lesion load, white matter or gray matter volumes) or clinical proxies of physical disability (i.e. the Expanded Disability Status Scale, EDSS) on cognition in Multiple Sclerosis (MS). A meta-analytic study with a meta-regression approach was performed to investigate the possible role of CR as moderator of the impact of brain damage and physical disability on cognition. Methods: Two literature searches were performed to retrieve all studies that investigated the relationship between MRI biomarkers and cognition, or the relationship between physical disability and cognition. Data about CR proxies (education, vocabulary knowledge, CR questionnaires) were also collected. We performed several meta-analyses with random effect models (Hedges’ g), and a moderator analysis with a meta-regression approach (with CR entered as a numerical moderator). A p value of < 0.05 was set for statistical significance. Results: We found a significant impact of lesion load and gray matter abnormalities on most cognitive domains. Meta-regression showed that CR significantly moderated the relationship between brain damage and verbal fluency. Moreover, we found a significant impact of physical disability on cognitive functioning, but CR did not mitigate the relationship between EDSS and cognitive performance. Conclusion: The present findings limit the protective role of CR against the impact of the brain damage to selected aspects of cognition (those related to lexical access and cognitive flexibility) in MS. These findings reinforce the need for longitudinal studies exploring the moderator effect of CR over the course of MS.