PROJECT SUMMARY/ABSTRACT Hypertension remains a leading contributor to cardiovascular disease-related morbidity and mortality in the United States. Older (i.e., ≥60 y) women are one group more likely to develop hypertension with inadequate blood pressure (BP) control, despite optimal drug regimens. Older women are also at a greater risk for the development of Alzheimer’s disease and related dementias which are exacerbated by hypertension. Accordingly, the prevalence of hypertension and ineffectiveness of drug treatments alone signal the need for non-pharmacological approaches to supplement standard care for BP control in this population. One such approach to achieve this is “heat therapy.” Recent studies have revealed the promising benefits of heat therapy on vascular health, autonomic activity, and cardiac function, which may ultimately reduce BP and the risk for cardiovascular diseases. These physiological adapta- tions may also translate to improvements in cognitive function through improved cerebrovascular func- tion and health. However, no information exists regarding the efficacy of heat therapy to reduce BP, induce meaningful neural-cardiovascular adaptations, and improve cognition in older women. The overall goals of this proposal will be to 1) identify changes in autonomic BP regulation and 2) assess alterations in cerebrovascular and cognitive function in older women with mild hyper- tension following 8 weeks of at-home heat therapy. Specific Aim 1 will investigate chronic lower leg heat therapy's impact on BP control and neural-cardiovascular function in older, hypertensive women using intervention and control groups. The intervention group will perform 8 weeks of at-home lower leg heat therapy using hot water immersion up to the knee (42°C, 45 min/session, 4 sessions/week). The control group will complete the same sessions with thermoneutral water (35°C). We will assess 24-hour ambulatory BP, sympathetic vascular transduction, cardiac function, and heat shock protein expression before and after the interventional period. Specific Aim 2 will measure cerebral hemody- namics and cognitive function responses to chronic lower leg heat therapy in older, hypertensive women. We will use transcranial Doppler ultrasound to assess cerebrovascular function and autoreg- ulation before and after 8 weeks of lower leg heat therapy. Further, we will use the NIH Toolbox Cog- nitive Battery to assess different cognitive function domains. To maximize the clinical relevance of this project and my scientific training, I have assembled a strong interdisciplinary research team comprised of Qi Fu, MD, PhD, Rong Zhang, PhD, Steven Romero, PhD, Heidi Rossetti, PhD, and Satyam Sarma, MD. This team will help me complete the proposed project and master several technical skills (e.g., microneurography, echocardiography, biomolecular assays), while improving my ability to obtain extra- mural research funding (e.g., NIH K99/R00) and become a successful independent cl...