frequency-specific low frequency oscillations to assess transmission to the brain and local autonomic control of blood
flow, and response to a visual task as an index of cerebrovascular reactivity to a stimulus.
Secondly, we will define indices of tissue vulnerability to injury from both MRI indices of microstructural injury, monogenic
genetic variants associated with cSVD and a polygenic index of tissue vulnerability from cSVD associated genes, not
associated with hypertension.
To test the hypothesised mechanism, we will screen >1000 clinical and demographic risk factors in UK Biobank for
consistent univariate associations with both these novel measures and imaging markers of cSVD (white matter
hyperintensities, DTI-indices), cognitive outcomes and algorithmically-defined clinical outcomes. We will then use structural
equation modelling with latent variables for vascular aging, cerebrovascular dysfunction, tissue vulnerability, structural
damage and clinical outcomes, to test the validity of this causative mechanism and provide a model to screen for potential
repurposable drugs used in other conditions.
