Cognitive reserve proxies predict cognition and motor function beyond multimodal MRI brain measures in healthy adults

Individual differences in cognitive reserve (CR) may moderate the association between brain characteristics and task performance, although the interplay between these factors and behavioural outcomes is unclear. Using multimodal magnetic resonance imaging (MRI), we explored whether proxies of CR or brain measures more strongly predict cognition and motor function in healthy adults. A total of 101 participants completed CR proxy, cognition, and motor function assessments. Structural, diffusion, and functional imaging measures were investigated. Associations between CR proxies, brain measures, and outcomes were explored using multiple linear regression. Controlling for demographics, CR proxy score was a significant moderator of the relationship between structurally derived brain measures and both cognition and motor function. CR proxy score was the only significant predictor of cognition and motor function, explaining variance beyond brain characteristics. MRI brain measures were not associated with overall cognition, overall motor function, or CR proxy score. CR proxies accounted for more variance in global cognition and all motor tests compared to brain measures; however, specific cognitive outcome test performance variance was more nuanced, often more strongly associated with brain measures. These findings highlight, for the first time, that proxies of CR account for differences in cognitive and motor function among healthy adults over and above what structural and functional brain characteristics can explain. Thus, CR appears to not only protect against brain changes, but also provides functional advantages in the absence of pathology, suggesting that greater engagement in stimulating experiences enhances healthy adult quality of life.