Abstract
It is of the utmost importance to identify possible determinants of brain ageing. Using valuable data from the Lothian Birth Cohort / Disconnected Mind study, and complementary data from UK Biobank, we report results from several studies investigating associations between key brain MRI and DTI parameters and potential risk factors (genetic status, vascular risk, cortisol). We use the large cross-sectional UK Biobank data to accurately characterise age differences in white matter tract microstructure (WMTM) and brain macrostructure, and identify selective relationships between these measures with APOE status and vascular risk. In the Lothian Birth Cohort studies, WMTM mediated associations between elevated reactive cortisol and cognitive ageing differences across 60 years. Additionally, selective vascular risk factors interacted with APOE status to predict 3-year growth in white matter hyperintensity volume. These results highlight potential targets for the amelioration of specific aspects of brain ageing.