Modelling cognitive outcomes in the UK Biobank: education, noradrenaline and frontoparietal networks

Cognitive reserve measured by proxies of life experiences is thought to account for the heterogeneity in cognitive ageing. One hypothesis is that cognitively enriched environments acting on the noradrenergic system strengthen the right fronto-parietal networks to facilitate cognitive reserve and maintain cognition throughout the lifetime. We used machine learning and mediation analysis to model interactions between neurobiological features (genetic variants in noradrenergic signalling, structural and functional fronto-parietal connectivity measures) and cognitive reserve (by proxy of education) on cognitive outcomes (general cognitive ability score) in the ageing UK Biobank cohort. We show that: (1) interactions between education and neurobiological variables more fully explain general cognitive ability than either factor alone; (2) among the examined neurobiological features, measures of fronto-parietal connectivity are the strongest mediators of the effect of education on cognitive outcomes. In particular, our findings point to two between-networks connectivity measures representing, connections linking the default mode network with the right fronto-parietal network, and with the executive control network as the key mediators between cognitively enriched environments and cognitive outcomes. ### Competing Interest Statement The authors have declared no competing interest.