Aging and The Renin-Angiotensin System in Elderly Hypertensive Individuals

描述(申请人提供)：Hajjar博士是希伯来老年人寿的老年病学家，也是哈佛医学院的医学讲师。候选人的长期目标是通过研究肾素血管紧张素系统(RAS)及其遗传学在老年人认知和功能障碍以及脑血流变化中的作用，成为高血压和老龄化领域的独立临床研究员。他将通过拟议的职业发展计划实现这一目标，其中包括：由Lewis Lipsitz博士和一个多学科(老年病学、高血压、神经心理学、生物统计学、遗传学、内分泌学和老年学)咨询委员会提供指导；在临床试验、神经血管超声、神经心理学和遗传流行病学方面的课程工作；在神经血管和神经心理学实验室进行培训；以及进行密切指导的以患者为导向的研究。最近的证据表明，RAS在衰老过程中发挥了作用。这位候选人在观察性研究中证明，使用抑制RAS的抗高血压药物治疗可能会减缓随着年龄的增长而出现的认知和功能衰退。该环境学术丰富，包括哈佛医学院内的各种组织和实验室，这些组织和实验室将培养成为独立研究人员的科学发展和研究技能。在利普西茨博士的指导下，该研究计划旨在为未来的研究活动收集初步数据。第一个项目是用血管紧张素受体阻滞剂、血管紧张素转换酶抑制剂(ACEI)和利尿剂对100名有早期记忆丧失或执行功能障碍客观证据的老年高血压患者进行为期6个月的试验性3臂随机临床试验。结果测量包括认知功能、体能和脑血流量。第二个项目是分析健康老龄化和身体成分调查的数据，以确定在未来的研究活动中是否有理由进行药物遗传学研究。这项分析将调查血管紧张素转换酶基因多态性与血管紧张素转换酶在老年人群(n=3,075)认知功能减退中的应用之间的相互作用。相关性：该项目的发现将为患有认知和身体损害的老年患者提供新的治疗方式。它还将使我们能够结合不同领域的专业知识，以增加我们对心血管疾病影响衰老的潜在机制的理解。

DESCRIPTION (provided by applicant): Dr. Hajjar is a geriatrician at Hebrew SeniorLife and an Instructor of Medicine at Harvard medical School. The candidate's long-term goal is to become an independent clinical investigator in the area of hypertension and aging by studying the role of the renin angiotensin system (RAS) and its genetics in cognitive and functional impairment and cerebral blood flow changes in the elderly. He will achieve this goal by a proposed career development plan that incorporates: mentorship by Dr. Lewis Lipsitz and a multidisciplinary (geriatrics, hypertension, neuropsychology, biostatistics, genetics, endocrinology, and gerontology) advisory committee; coursework in clinical trials, neurovascular ultrasonography, neuropsychology, and genetic epidemiology; training at neurovasuclar and neuropsychological laboratories; and conduct of a closely mentored patient-oriented research. Recent evidence suggests that RAS plays a role in aging. The candidate has demonstrated in observational studies that treatment with antihypertensives that inhibit RAS may slow down cognitive and functional decline with aging. The environment is academically rich and includes the various organizations and laboratories within the Harvard Medical School which will foster the scientific development and research skills to become an independent researcher. Under the mentorship of Dr. Lipsitz, the research plan is designed to gather preliminary data for future research activities. The first project is to conduct a pilot 3-arm randomized clinical trial of 6-month treatment with an angiotensin receptor blocker, an angiotensin converting enzyme inhibitor (ACEI), and a diuretic in seniors (n=100) with hypertension and objective evidence of early memory loss or executive dysfunction. The outcome measures include cognitive function, physical abilities and cerebral blood flow. The second project is to analyze data from the Health Aging and Body Composition survey to determine if a pharmacogenetic study is justifiable in the future research activities. This analysis will investigate the interaction between angiotensin converting enzyme gene polymorphism and the use of ACEI on cognitive decline in an aging population (n=3,075). Relevance: Findings from this project would provide new treatment modalities for elderly patients suffering from cognitive and physical impairment. It will also allow us to combine expertise from various fields to increase our understanding of the underlying mechanism by which cardiovascular disease affects aging.