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

高血压对高龄老人痴呆和慢步态的保护作用机制

• 批准号: 9014428
• 负责人: Szofia S Bullain
• 金额: $ 15.4万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9014428
• 关键词: Age; Aged, 80 and over; Aging; Autopsy; Award; Blood Pressure; Blood Vessels; Blood flow; Brain; California; Cardiology; Cerebrovascular Circulation; Cerebrum; Clinical; Comorbidity; Complex; Cross-Sectional Studies; Data; Dementia; Development; Educational workshop; Elderly; Ensure; Environment; Epidemiology; Faculty; Foundations; Gait; Goals; Guidelines; Hypertension; Impairment; Individual; Institutes; Investigation; K-Series Research Career Programs; Knowledge; Longitudinal Studies; Measurement; Measures; Mediating; Medical; Memory impairment; Mentors; Methodology; Modeling; Neurologist; Neurology; Participant; Perfusion; Pharmaceutical Preparations; Physical Performance; Physicians; Physiologic pulse; Physiological; Positioning Attribute; Prevalence; Prevention; Preventive; Process; Public Health; Research; Research Training; Resource Development; Risk; Risk Factors; Role; Scientist; Series; Testing; Time; Training; Universities; Walking; Work; aged; arterial stiffness; blood pressure regulation; career development; cerebrovascular; cohort; hypertension treatment; nervous system disorder; neuroimaging; neuropathology; novel; patient oriented; programs; protective effect; public health relevance; response; systolic hypertension

 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.

 描述（由申请人提供）：候选人是一名医生科学家和一名委员会认证的神经学家，专门从事老年神经病学。在这个指导病人为导向的职业发展奖提出的培训和研究计划将推动候选人走向学术独立。该奖项将支持她对高血压对最年长者（90岁及以上）的缓慢步态和痴呆症的保护作用的研究。她将获得动脉硬度（AS）和脑血流量（CBF）的非侵入性测量的专业知识，并将完成公共卫生计划的兼职硕士学位，这将为她的长期目标做好准备：为针对晚期认知和身体障碍的公共卫生预防工作做出贡献。候选人在老年神经病学，流行病学和心脏病学方面的专业知识将通过应用程序对与年龄相关的血管变化在晚期痴呆和缓慢步态中的作用的关注而得到加强。此外，该奖项的拟议目标将为更大规模的研究应用奠定基础（例如，R01），并确保申请人的发展走向学术独立。环境加州大学欧文分校提供一系列独特的培训和发展资源，以促进候选人晋升为独立的学术医生科学家。其中包括一个支持性的主席和一个由神经病学系和记忆障碍和神经疾病研究所的杰出教师组成的合作小组，一个特殊的导师团队（Claudia Kawas博士），共同导师（黄博士），及合作者（Michael Yassa博士），访问美国最大的特征明确的高龄受试者队列（90+研究），最先进的神经成像设施，以及各种课程和研讨会，将加速申请人在整个奖项期间的职业发展。research.高血压（HTN）与年轻老年人痴呆和步态缓慢的风险增加有关。然而，HTN似乎是保护最古老的。这种保护作用的机制尚不清楚，也不能通过使用HTN或其他医学合并症的药物来解释。候选人假设，HTN在最老的老年人代表了生理代偿机制，以保持足够的脑灌注，面对年龄相关的动脉僵硬度（AS）。AS的患病率随着年龄的增长而增加，在年轻的老年人中，AS与痴呆和缓慢步态有关。因此，具体目标1旨在确定AS与痴呆和缓慢步态之间的关联是否因高龄老人中HTN的存在而变化。脑灌注（CBF）随着AS和HTN的变化而变化，因此特定目标2的目标是确定高血压对痴呆和缓慢步态的保护作用是否可以通过高龄老人的CBF来解释。最后，具体目标3旨在确定AS和CBF之间的关联是否因最年长者的HTN状态而异。这些数据将直接有助于针对晚期痴呆和步态缓慢的公共卫生工作，也可能为制定针对高龄老人的特定年龄HTN管理指南提供依据。