The mechanism of hypertension's protective effect on dementia and slow gait in the oldest-old

University Of California-Irvine, Irvine CA

Investigators

Abstract

? DESCRIPTION (provided by applicant): The candidate is a physician scientist and a board-certified neurologist specializing geriatric neurology. The training and research plan proposed in this Mentored Patient-Oriented Career Development Award will propel the candidate toward academic independence. This award will support her investigation of the protective effect of hypertension on slow gait and dementia in the oldest-old; people aged 90 and older. She will gain expertise in the non-invasive measurement of arterial stiffness (AS) and cerebral blood flow (CBF) and will complete a part-time Master in Public Health program that will prepare her for her long-term goal: to contribute to the public health prevention efforts that target late-age cognitiv and physical impairment. The candidate's expertise in geriatric neurology, epidemiology and cardiology will be strengthened by the application's focus on the role of age-associated vascular changes in late-age dementia and slow gait. Furthermore, the proposed goals of the award will lay the foundation of a larger scale research application (e.g., R01) and ensure the applicant's development towards academic independence. Environment. The University of California, Irvine offers a unique array of training and development resources to facilitate the candidate advancing to an independent, academic physician scientist position. These include a supportive Chair and a collaborative group of distinguished faculty in the Department of Neurology and at the Institute for Memory Impairments and Neurological Disorders, an exceptional team of mentor (Dr. Claudia Kawas), co-mentor (Dr. Nathan Wong), and collaborator (Dr. Michael Yassa), access to the largest cohort of well-characterized oldest-old subjects in the USA (The 90+ Study), state-of-the-art neuroimaging facilities, and a variety of courses and workshops that will accelerate the applicant's career development throughout the duration of this award. Research. Hypertension (HTN) is associated with increased risk of dementia and slow gait in younger elderly. However, HTN appears to be protective in the oldest-old. The mechanism of this protective effect is unknown, and not explained by the use of medications for HTN or other medical comorbidities. The Candidate hypothesizes that HTN in the oldest-old represents a physiological compensatory mechanism to maintain adequate cerebral perfusion in the face of age-associated arterial stiffness (AS). The prevalence of AS increases with age, and in younger elderly AS is associated with dementia and slow gait. Therefore, Specific Aim 1 seeks to determine if the association between AS and dementia and slow gait varies by the presence of HTN in the oldest-old. Cerebral perfusion (CBF) changes with AS and HTN, thus the goal of Specific Aim 2 is to determine if the protective effect of hypertension on dementia and slow gait is explained by CBF in the oldest-old. Lastly, Specific Aim 3 seeks to determine if the association between AS and CBF varies by HTN status in the oldest-old. These data will directly contribute to the public health efforts that target late-age dementia and slow gait, and may also provide rationale for the development of age-specific HTN management guidelines for the oldest-old.