Antihypertensives and the Aging Brain

项目摘要/摘要 求职者的长期职业目标是确定普通内科的治疗策略 对晚年大脑健康有有益影响的疾病。职业生涯的短期目标 考生要：发展因果推理方法的关键研究技能，对以下方面有基本的了解 与痴呆症相关的神经病理学，了解痴呆症的诊断和神经心理测试 临床护理，培养沟通技能，为地方和国家的领导能力奠定坚实的基础。 成功完成拟议的研究和职业发展计划将使应聘者 成为痴呆症药物流行病学的独立研究员和国家领导者-这是一个 这是发现的绝佳机会。在一定程度上，这将通过课程作业和指导学习来实现。 经验和与研究相关的活动。这些经验将使应聘者获得实际技能。 这可以直接应用于拟议的K76研究，以提高研究效率。保罗·B。 Beeson Emerging Leaders职业发展奖将提供必要的资源， 培训和指导，以实现这些职业目标和目的。 这项拟议研究的长期目标是使用脑保护剂预防或延缓痴呆症 抗高血压药。这项研究的具体目的是：1)检验假设，在控制 它们对血压、暴露于血管紧张素(Ang)-II#药物(与Ang-II$药物相比)的影响将是 与较低的阿尔茨海默病(AD)和非AD痴呆症风险相关；以及2)测试是否在 控制其对血压的影响，暴露于Ang-II#药物(与Ang-II$药物相比)将 与神经病理的标准标记物独立相关，包括Braak分期、CERAD 水平、囊性梗塞、微梗塞和路易小体，以及神经毒性的高度定量测量 多肽、炎症和神经胶质增生症，并增加了对 神经病理学，如这些神经病理学指标与痴呆症预后之间的关联 会变得更弱。目的1可能有助于指导成人高血压的治疗，以优化大脑健康。目标2将 提供证据以了解抗高血压药物和高血压之间的任何联系的生物学基础 痴呆症。总而言之，这份Beeson K76提案概述了培训和有指导的研究活动，以支持 Zachary A.Marcum，药学博士，博士的职业发展朝着他成为一名独立的- 资助翻译科学家研究改善老年人大脑健康的方法。美国商务部 华盛顿大学和Kaiser Permanente华盛顿健康研究所药学 将为候选人提供一个丰富的环境。

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.