Unraveling the Protective Effects of Cognitive Reserve on Cognition and Brain: A Cross-Sectional Study

This study aimed to investigate the hypothesis that brain maintenance expressed in white matter hyperintensities and brain reserves, defined as gray and white matter volumes, mediate the association between cognitive reserve (CR) and cognitive performance. A cross-sectional population-based observational study was conducted, and the final study sample consisted of 763 participants (282 men and 481 women) with a mean age of 61.11 years (±9.0). Data from different categories were collected from study participants, such as demographic, lifestyle, medical, and psycho-social characteristics. All participants underwent a detailed psychometric evaluation (MoCA and DSST) followed by a brain MRI. Volumetric measurements of the total gray matter (GMvol), total white matter (WMvol), and white matter hyperintensities (WMHvol) were performed using the Computational Anatomy Toolbox 12 (CAT12) and Statistical Parametric Maps 12 (SPM12) based on 3D T1-weighted sequence. Significant direct and indirect effects of cognitive reserve on cognitive functioning were measured with both scales-the MoCA and DSST. In each mediation model, the volumes of WMH and GM were significant mediators for the association between cognitive reserve and cognitive performance. This study confirms the importance of strengthening the cognitive reserve in the course of life through potentially modifiable effects on both cognition and the brain.