Antihypertensives and the Aging Brain

抗高血压药和大脑老化

基本信息

批准号：
10183125
负责人：
Zachary Adam Marcum
金额：
$ 22.79万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10183125
关键词：
Adult Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos 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

项目摘要

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.

项目概要/摘要候选人的长期职业目标是确定常见医疗问题的治疗策略对晚年大脑健康产生有益影响的条件。候选人将：培养因果推理方法的关键研究技能，获得基本的了解痴呆相关的神经病理学，了解痴呆的诊断和神经心理学测试临床护理，培养沟通技巧，为地方和国家领导力奠定坚实的基础。成功完成拟议的研究和职业发展计划将为候选人定位成为痴呆症药物流行病学领域的独立研究者和国家领导者在某种程度上，这将通过课程作业和指导学习来实现。这些经验将使候选人获得实践技能。可以直接应用于拟议的 K76 研究，以提高研究效率。比森老龄化领域新兴领导者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。这项研究的长期目标是使用脑保护剂来预防或延缓痴呆症本研究的具体目的是：1）在控制后检验假设。接触血管紧张素 (Ang)-II# 药物（与 Ang-II$ 药物相比）对血压的影响与阿尔茨海默病 (AD) 和非 AD 痴呆症的较低风险相关；2) 测试是否控制其对血压的影响，接触 Ang-II# 药物（与 Ang-II$ 药物相比）将与神经病理学标准标志物有独立关联，包括 Braak 分期、CERAD 水平、囊性梗塞、微梗塞和路易体，以及神经毒性的高度定量测量使用多重 Histelide 检测来检测肽、炎症和神经胶质增生，并提高对以下因素影响的恢复能力神经病理学，以便这些神经病理学测量与痴呆结果之间的关联目标 1 可能有助于指导成人高血压的治疗，以优化大脑健康。提供证据以了解抗高血压药物和药物之间任何关联的生物学基础总之，这项 Beeson K76 提案概述了支持痴呆症的培训和指导研究活动。扎卡里·A·马库姆 (Zachary A. Marcum) 药学博士、博士的职业发展，旨在实现成为一名独立的资助转化科学家研究改善老年人大脑健康的方法。华盛顿大学药房和凯撒永久华盛顿健康研究所将为候选人提供丰富的环境。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Beliefs about benefits and harms of medications and supplements for brain health.

关于药物和补充剂对大脑健康的益处和危害的信念。

DOI：
10.1016/j.pmedr.2020.101060
发表时间：
2020
期刊：
Preventive medicine reports
影响因子：
2.8
作者：
Marcum,ZacharyA;Hohl,SarahD;Barthold,Douglas;Zaslavsky,Oleg;Larson,EricB;Gray,ShellyL
通讯作者：
Gray,ShellyL

Dietary Supplement Use in Middle-aged and Older Adults.

中老年人膳食补充剂的使用。

DOI：
10.1007/s12603-022-1732-9
发表时间：
2022
期刊：
The journal of nutrition, health & aging
影响因子：
0
作者：
Tan,ECK;Eshetie,TC;Gray,SL;Marcum,ZA
通讯作者：
Marcum,ZA

Toward a broader concept of societal value: family spillovers in Alzheimer's disease.

DOI：
10.1017/s0266462321000593
发表时间：
2021-12-20
期刊：
INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE
影响因子：
3.2
作者：
Park, Jenny Yeonhee;Marcum, Zachary A.;Garrison, Louis P.
通讯作者：
Garrison, Louis P.

Prescribing Alzheimer's Disease treatments by provider type and geographic region: a comparison among physicians, nurse practitioners, and physician assistants.

DOI：
10.1186/s12877-022-03176-3
发表时间：
2022-06-25
期刊：
BMC GERIATRICS
影响因子：
4.1
作者：
Park, Jenny Y.;Veenstra, David L.;Wallick, Christopher J.;Marcum, Zachary A.
通讯作者：
Marcum, Zachary A.

The use of narrative electronic prescribing instructions in pharmacoepidemiology: A scoping review for the International Society for Pharmacoepidemiology.

DOI：
10.1002/pds.5331
发表时间：
2021-10
期刊：
Pharmacoepidemiology and drug safety
影响因子：
2.6
作者：
Romanelli RJ;Schwartz NRM;Dixon WG;Rodriguez-Watson C;Sauer BC;Albright D;Marcum ZA
通讯作者：
Marcum ZA