Grant: Project Grant - PA: Sex and Gender in Health Research (Bridge funding)

Vascular diseases such as heart attacks and stroke are the main cause of death in females, and females diagnosed with these diseases are more likely to die from them than males. Despite this, most studies investigate vascular diseases in males, since females are commonly thought to be protected against them. Though there is evidence for a protective effect of estrogen, the lower estrogen levels after menopause leave females vulnerable to developing vascular diseases in later life. The decades following menopause often see the development of inflammation and vascular risk factors, including an increased stiffness of blood vessels. We currently know little about the role of estrogen and inflammation in mediating the link between vascular changes such as arterial stiffness and cerebral health across the lifespan in females. This knowledge is crucial if we are to eliminate the chasm in detection, management and prognosis of vascular diseases in aging females. The aims of this work are to: 1. Determine the timeline of vascular and cerebral changes across the lifespan in females; 2. Understand the link between large artery stiffness and cerebral changes; 3. Investigate the role of inflammation on the link between vascular and cerebral health; Magnetic resonance imaging is an ideal tool for studying these effects as it can be used for measurement of cerebral health, and carotid stiffness. MRI will be used with ultrasound and metabolomics to identify key relationships between estrogen, cerebral health, vascular stiffness and inflammation in 275 females across the adult lifespan. This work is the first step in studying the changes in vascular and cerebral health in females across the lifespan, and how these changes are related to estrogen and menopause. The knowledge gained will enable future studies on the sex-specific impact of lifestyle and exercise to better preserve cerebral and cognitive health.