Antihypertensives and the Aging Brain

抗高血压药和大脑老化

• 批准号: 9982746
• 负责人: Zachary Adam Marcum
• 金额: $ 23.03万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982746
• 关键词: Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; American; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animal Model; Antihypertensive Agents; Area; Autopsy; Biological; Biological Assay; Blood Pressure; Brain; Calcium Channel Blockers; Clinical; Cohort Studies; Communication; Data; Data Set; Dementia; Development Plans; Diagnosis; Dihydropyridines; Doctor of Pharmacy; Doctor of Philosophy; Drug Industry; Elderly; Enrollment; Environment; Exposure to; Foundations; Funding; Gliosis; Goals; Guidelines; Health; Hypertension; Impaired cognition; Incidence; Infarction; Inflammation; K-Series Research Career Programs; Late Onset Alzheimer Disease; Leadership; Learning; Lewy Bodies; Link; Longitudinal Studies; Longitudinal observational study; Measurement; Measures; Medical; Medical Records; Mentors; Methods; Neuropsychological Tests; Observational Study; Outcome; Outcome Measure; Participant; Peptides; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacy facility; Positioning Attribute; Prevention; Productivity; Program Development; Randomized Controlled Trials; Research; Research Activity; Research Institute; Research Methodology; Research Personnel; Resources; Testing; Therapeutic; Thiazide Diuretics; Training; Universities; Washington; aging brain; base; brain health; cardiovascular risk factor; career; career development; clinical care; dementia risk; epidemiological model; evidence base; experience; follow-up; hypertension treatment; improved; neuropathology; neurotoxic; nonalzheimer dementia; novel; prevent; receptor; research and development; resilience; skills; translational scientist; treatment choice; treatment guidelines; treatment strategy

PROJECT SUMMARY/ABSTRACT The long-term career goal of the candidate is to identify treatment strategies for common medical conditions that have beneficial impacts on brain health in late-life. The short-term career objectives of the candidate are to: develop key research skills in causal inference methods, gain a basic understanding of dementia-related neuropathology, learn about the diagnosis of dementia and neuropsychological testing in clinical care, and develop communication skills and build strong foundations for local and national leadership. Successful completion of the proposed research and career development program will position the candidate to become an independent investigator and national leader in dementia pharmacoepidemiology – an area of great opportunity for discovery. In part, this will be accomplished through coursework, mentored learning experiences, and research-related activities. These experiences will allow the candidate to gain practical skills that can be directly applied to the proposed K76 research to enhance research productivity. The Paul B. Beeson Emerging Leaders Career Development Award in Aging would provide the necessary resources, training, and mentoring to achieve these career goals and objectives. The long-term objective of this proposed research is to prevent or delay dementia using brain-protectant antihypertensives. The specific aims of this research are to: 1) test the hypothesis that after controlling for their effects on blood pressure, exposure to Angiotensin (Ang)-II# drugs (compared with Ang-II$ drugs) will be associated with lower risk of Alzheimer’s Disease (AD) and non-AD dementias; and 2) test whether, after controlling for their effects on blood pressure, exposure to Ang-II# drugs (compared with Ang-II$ drugs) will have an independent association with standard markers of neuropathology, including Braak stage, CERAD level, cystic infarcts, microinfarcts, and Lewy bodies, as well as highly quantitative measures of neurotoxic peptides, inflammation, and gliosis using a multiplexed Histelide assay, and increase resilience to the effects of neuropathology, such that the association between these neuropathology measures and dementia outcomes will be weaker. Aim 1 may help guide treatment of hypertension in adults to optimize brain health. Aim 2 will provide evidence to understand the biological basis of any association between antihypertensives and dementia. In summary, this Beeson K76 proposal outlines training and mentored research activities to support the career development of Zachary A. Marcum, PharmD, PhD toward his goal of becoming an independently- funded translational scientist researching methods to improve brain health for older adults. The Department of Pharmacy at the University of Washington and the Kaiser Permanente Washington Health Research Institute will provide a rich environment for the candidate.

项目摘要/摘要 候选人的长期职业目标是确定普通医学的治疗策略 对晚年大脑健康产生有益影响的疾病。短期职业目标 候选人要：在因果推理方法中培养关键的研究技能，对 与痴呆相关的神经病理学，了解痴呆症的诊断和神经心理学测试 临床护理，并发展沟通技巧，并为地方和国家领导层建立强大的基础。 成功完成拟议的研究和职业发展计划将使候选人定位 成为痴呆症药物学的独立研究员和国家领导者 - 一个领域 发现的绝佳机会。在某种程度上，这将通过课程工作，指导学习 经验和与研究相关的活动。这些经验将使候选人获得实践技能 可以将其直接应用于拟议的K76研究以提高研究生产率。保罗·B（Paul B.） Beeson新兴领导者衰老职业发展奖将提供必要的资源， 培训和心理以实现这些职业目标和目标。 这项拟议的研究的长期目标是使用脑保护剂预防或延迟痴呆症 抗高血压。这项研究的具体目的是：1）检验以下假设：在控制之后 它们对血压，血管紧张素（ANG）-II＃药物的影响（与ANG-II $药物相比）将是 与阿尔茨海默氏病（AD）和非AD痴呆症的较低风险有关； 2）测试是否在 控制它们对血压的影响，暴露于ANG-II＃药物（与Ang-II $ press相比）将 与神经病理学的标准标记有独立的联系，包括Braak阶段，Cerad 水平，囊性实际，微吸收和路易的身体，以及高度定量的神经毒性测量值 肽，感染和神经胶质细胞增多使用多路复用组织测定法，并提高弹性 神经病理学，使这些神经病理学措施与痴呆症结果之间的关联 会弱。 AIM 1可能有助于指导成年人的高血压治疗以优化大脑健康。 AIM 2意志 提供证据以了解抗高血压与 失智。总而言之，这项Beeson K76提案概述了培训并修改了研究活动以支持 Zachary A. Marcum，Pharmd，Pharmd博士的职业发展，他成为独立的目标 - 资助的翻译科学家研究方法可以改善老年人的大脑健康。部门 华盛顿大学的药房和Kaiser Permanente Washington Health Research Institute 将为候选人提供丰富的环境。