Project Summary/Abstract Cardiovascular risk factors have been implicated in Alzheimer's disease and related dementias, however, mechanisms underlying heart-brain hemodynamic coupling are not well understood. Aortic stiffening has been associated with increased dementia risk. In addition to brain changes typically associated with aging, cerebrovascular disease and Alzheimer's disease also affect vascular function and neuronal structure. However, the heart and brain are not usually evaluated in the same MRI exam, rather, in separate scanning sessions with highly specialized protocols focused on either cardiovascular or brain imaging. Recently, our group and others have established advanced MRI techniques to capture measures such as cardio- and cerebrovascular hemodynamics and brain structure in the same MRI exam. Measuring aortic hemodynamics (e.g., pulse wave velocity), together with intracranial pulsatility and brain abnormalities associated with cerebrovascular disease and Alzheimer's disease, will provide critical insights concerning underlying hemodynamic mechanisms. The proposed research will use advanced MRI techniques for comprehensive analysis of heart-brain hemodynamic coupling. This project will leverage new developments in cardiovascular imaging, particularly using 4D flow MRI, that enable full characterization of complex 3D hemodynamics, such as blood flow velocity, reverse flow mapping and aortic pulse wave velocity. Methodological advances in highly accelerated 4D flow MRI enable integration of cardiovascular and intracranial 4D flow MRI with quantitative structural analysis of the brain in a single MRI exam. This combined cardio- and cerebrovascular 4D flow MRI with quantitative brain imaging (i.e. “heart-brain MRI”) will be used to analyze hemodynamic coupling in aging and Alzheimer's disease. The goal of this proposal is to use novel heart-brain MRI to systematically evaluate hemodynamic coupling relationships in normal aging, and hypertension, and apply this technique in a pilot study of Alzheimer's disease. In Aims 1 and 2, heart-brain MRI will be evaluated in healthy adults and those with hypertension at both midlife and later life, to determine relationships between heart-brain MRI measures in normal aging and how hypertension may exacerbate brain changes with aging. In Aim 3, heart-brain MRI will be applied in a pilot study of Alzheimer's disease to examine preliminary relationships and help plan future studies. This K01 will provided training in clinical and neuroimaging aspects of aging and Alzheimer's disease to further the objective of building an independent research program focused on heart-brain hemodynamic coupling in cognitive aging and dementia, including that caused by Alzheimer's disease.

Project Narrative The long-term goal of this research is to elucidate the mechanisms by which cardiovascular risk factors lead to increased risk for dementia with aging. By understanding these mechanisms, it will be possible to help inform design of new approaches to delay or prevent the debilitating impacts of dementia, including that caused by Alzheimer's disease. The end result will be to improve quality of life for those suffering from dementia, and the subsequent impacts on their caregivers.