Elevated blood pressure variability (BPV) is a risk factor for cerebral small vessel disease, neurodegeneration, and dementia, even when average blood pressure levels are aggressively controlled. Not all individuals with high BPV develop neurodegeneration and dementia, and the susceptibility factors that underly this differential burden are not understood. Additionally, therapeutics that manage BPV or BPV susceptibility factors have not been identified. To address these knowledge gaps we are analyzing potential susceptibility factors to neurodegeneration related to elevated BPV, and therapeutics with the potential to modify BPV or susceptibility to BPV in order to answer the following research questions:1) What is the role of reactive astrogliosis in BPV-induced neurodegenerative pathophysiology, 2) What is the role of cerebrovascular dysfunction in BPV-induced neurodegenerative pathophysiology, 3) What is the role of impaired angiogenic signaling in BPV-induced neurodegenerative pathophysiology, 4) Does strict adherence to an antihypertensive medication regime reduce BPV, 5) Do brain-penetrant antihypertensive medications reduce BPV or the adverse effects of elevated BPV, and 6) Does the presence of at least one copy of the APOE4 allele modify any of these relationships.
