Dissociable contributions of cortical thickness and surface area to cognitive ageing: evidence from multiple longitudinal cohorts.

Cortical volume, a widely-used marker of brain ageing, is the product of two genetically and developmentally dissociable morphometric features: thickness and area. However, it remains unclear whether these two features have dissociable consequences for cognitive ageing. To address this, we analyse cross-sectional and longitudinal neuroimaging and cognitive data from one discovery cohort (Cam-CAN) and two independent, pre-registered replication cohorts (OASIS-3 and HABS-HD), leveraging wide age ranges across adulthood, different follow-up intervals and diverse population backgrounds. We show that thickness declines more steeply with age than does area, and shows stronger associations with longitudinal change in fluid cognitive abilities, fairly uniformly across the cortex. Cognitive change is also dependent on baseline thickness, independent of thickness change and independent of baseline cognitive ability. In contrast, area is comparatively stable across adulthood, at least until old age, and shows weaker and more heterogeneous associations with cognitive change, despite being a stronger mediator of the effect of polygenic scores on baseline cognitive ability. Together, these findings help to reconcile inconsistencies in the literature, and indicate that thickness provides a more sensitive marker of dynamic neurobiological processes underlying cognitive ageing, whereas area seems to reflect primarily stable, trait-like variation in cognitive ability.