Cerebral Hemodynamics and Brain Health in Adults with and without Symptoms of Autonomic Dysfunction

Autonomic dysfunction remains underdiagnosed and misunderstood but is a significant healthcare burden that affects millions of people in the United States. Autonomic disturbances are present in 40% of neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease, and other dementias and is often coupled with higher markers of cerebrovascular pathology. In this context, cerebrovascular health and autonomic function may be linked, but the connection is unknown. Additionally, little is understood about the contribution of autonomic dysfunction in tandem with drivers of cerebrovascular pathology on vascular contributions to cognitive impairment and dementia (VCID). The overarching objective of this proposal is to elucidate the link between drivers of cerebrovascular pathology and autonomic dysfunction and identify the impact on VCID biomarkers. Our preliminary data demonstrate that elevated cerebral pulsatility is associated with greater VCID biomarkers (e.g. white matter hyperintensities, WMH) in cognitively normal adults, and our published data demonstrate that adults with lower cardiovascular responses to physiological stressors are associated with greater WMH in healthy adults. Therefore, the central hypothesis is that disrupted cerebral hemodynamics will associate with impaired autonomic function, and together these contribute to greater VCID biomarkers. To test this hypothesis, I will use state-of-the-art magnetic resonance imaging (MRI) and the novel 4D flow MRI technique to measure cerebral hemodynamics (e.g., cerebral pulsatility and cerebral blood flow, CBF) in collaboration with experts in the field of MRI (e.g., Dr. Wieben, Co-sponsor). Additionally, I will use gold-standard techniques to directly measure autonomic function (e.g., sympathetic nerve activity, SNA; baroreflex sensitivity, BRS; and cardiovascular responses). Lastly, I will assess VCID neuroimaging biomarkers (e.g. WMH and cerebrovascular reactivity, CVR), and evaluate the associations between cerebral hemodynamics or autonomic function and these VCID biomarkers. Aim 1 will examine cerebral hemodynamics in middle-aged adults with and without symptoms of autonomic dysfunction. Aim 2 will determine the impact of cerebral hemodynamics and autonomic function on VCID biomarkers in middle-aged adults with and without symptoms of autonomic dysfunction. Collectively, these data will determine the link between cerebral hemodynamic and autonomic function and their contributions to brain health. The proposed work, in conjunction with the comprehensive training plan, will assist in the development of a scientific niche in the field and ensure success through the transition from a predoctoral trainee to a postdoctoral fellowship position. In addition, outcomes from this project will have broader implications for how to prevent or treat autonomic dysfunction that could also benefit brain health. Project Number: 1F31NS147710-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Sarean Harmoni Sumner | Institution: UNIVERSITY OF WISCONSIN-MADISON, MADISON, WI | Award Amount: $38,646 | Activity Code: F31 | Study Section: Special Emphasis Panel[ZRG1 F01A-N (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11317996