The Protective Power of Cognitive Reserve: Examining White Matter Integrity and Cognitive Function in the Aging Brain for Sustainable Cognitive Health

Sustainable cognitive health is heavily influenced by cognitive reserve (CR), which delays cognitive decline or reduces its severity by enhancing cognitive function through life experiences. The main objective of this study is to explore whether CR moderates the relationship between white matter integrity and cognitive function in cognitively intact older adults. A cross-sectional analysis was conducted on 5004 cognitively normal individuals aged 48-80 years from the UK Biobank, utilizing hierarchical regression analysis to estimate CR through five CR proxies and five skeleton-based diffusion measures. The study's findings revealed that early fluid intelligence had a significant independent and moderating impact on cognitive performance, demonstrating its suitability as an individual CR proxy. Moreover, the composite proxy composed of early fluid intelligence and physical activity showed promise in promoting sustainable cognitive health. Importantly, this study represents one of the most extensive MRI investigations to unveil the substantial moderating effect of CR on the intricate relationship between white matter integrity and cognitive function based on a complete model. Notably, this study employed the NODDI method, which proved more advantageous than DTI in examining this interaction. Overall, this research constitutes a noteworthy and substantive contribution to our current understanding of the complex and intricate relationship between CR, cognitive function, and aging-associated cognitive decline, highlighting the importance of considering CR proxies in promoting sustainable cognitive health in aging populations.