Age-Related Differences in Human Cortical Microstructure Depend on the Distance to the Nearest Vein

Age-related differences in cortical microstructure are used to understand the neuronal mechanisms that underlie human brain ageing. The cerebral vasculature contributes to cortical ageing, but its precise influence on age-related differences in cortical microstructure is poorly understood. In a cross-sectional study, we combine venous imaging with vessel distance mapping (VDM) to investigate the influence of venous distances on age-related differences in the microstructural architecture of the cortex. We focus on primary somatosensory cortex (S1) and primary motor cortex (M1) as both show age-related alterations linked to neurodegeneration and behavioural decline. We scanned 18 younger adults and 17 older adults at a 7T MRI scanner to measure age-related changes in quantitative T1 (qT1) values and positive QSM (pQSM) values at 0.5 mm isotropic resolution as proxies for cortical myelin and cortical iron content, respectively. We modelled different cortical depths using an equi-volume approach and assessed the distance of each voxel in each layer to its nearest vein using VDM. Our data reveal a dependence both of cortical qT1 and cortical pQSM values on venous distance. In addition, there is an interaction between venous distance and age on qT1 values, driven by lower myelination in older compared to younger adults in voxels that are farther away from a vein and higher myelination in older adults in voxels that are closer to a vein. This effect is particularly pronounced in M1 and indicates that the venous distance may act as a protective mechanism in healthy ageing. Together, our data show that the local venous architecture explains a significant amount of variance in standard measures of cortical microstructure, and should be considered in neurobiological models of human brain organisation and cortical ageing. ### Competing Interest Statement The authors have declared no competing interest.