Pharmaconeuropathology of Brain Aging and Dementia

脑衰老和痴呆的药物神经病理学

• 批准号: 7884081
• 负责人: JOSHUA A SONNEN
• 金额: $ 33.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884081
• 关键词: Adult; Alzheimer' s Disease; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Antihypertensive Agents; Antioxidants; Aspirin; Autopsy; Back; Biochemical; Biological Assay; Brain; Calcium Channel Blockers; Cerebrum; Chronic; Clinical; Clinical Trials; Data; Databases; Dementia; Diabetes Mellitus; Diagnosis; Disease; Disincentive; Dose; Drug Exposure; Drug Industry; Drug Prescriptions; Drug usage; Elderly; Exercise; Foundations; Goals; Gold; Grant; Health; Hormone replacement therapy; Individual; Intervention; Legal patent; Lewy Body Disease; Longitudinal Studies; Manuscripts; Nerve Degeneration; Neuroprotective Agents; Non-Steroidal Anti-Inflammatory Agents; Observational Study; Oxidoreductase; Participant; Pathologic; Pharmaceutical Preparations; Pharmacologic Substance; Phenotype; Population Attributable Risks; Preparation; Process; Public Health; Randomized Clinical Trials; Regimen; Research; Research Personnel; Resources; Risk; Smoking; Staging; Stress; Syndrome; Testing; Therapeutic; Time; United States National Institutes of Health; Validation; Woman; aging brain; comparative effectiveness; hypertension treatment; inhibitor/antagonist; neuroimaging; neuropathology; next generation; novel; population based; pre-clinical; prevent

DESCRIPTION (provided by applicant): Dementia in the elderly is a chronic syndrome with multiple causes that is already major public health burden and presents a clear therapeutic imperative to biomedical researchers. Given the time and expense of randomized clinical trials (RCTs) focused on preventing or delaying incident dementia, there is a critical public health need to validate therapies quickly and robustly to insure that the best possible candidates advance to RCTs. This application is a competitive renewal of Pharmaco- neuropathology of Brain Aging and Dementia that exploits the tremendous and unique resources of the Adult Changes in Thought Study, a large population-based longitudinal study of brain aging and incident dementia in older individuals, to identify potentially effective therapeutics for advancement to clinical trials. In this competitive renewal, we propose to determine the associations between the following mid- and late-life exposures or activities and neuropathologic, structural, and biochemical features of dementia in the elderly: "cardioprotective" doses of aspirin, hormone replacement therapy in women, two subclasses of antihypertensive drugs with proposed neuroprotective actions (calcium channel blockers and angiotensin-converting enzyme inhibitors), and level of physical exercise. These observational data will provide a unique perspective on which commonly prescribed drugs or exercise suppress specific mechanisms of disease, thereby guiding research on comparative effectiveness and aiding in the selection of regimens to pursue in RCTs.

描述(申请人提供)：老年痴呆症是一种具有多种原因的慢性综合征，已经成为主要的公共卫生负担，并向生物医学研究人员提出了明确的治疗需求。考虑到专注于预防或延迟偶发性痴呆的随机临床试验(RCT)的时间和费用，迫切需要快速而有力地验证治疗方法，以确保最好的候选者进入RCT。这项应用是脑老化和痴呆的药物神经病理学的竞争性更新，它利用了成人思维变化研究的巨大和独特的资源，这是一项关于老年人大脑老化和痴呆症事件的大型人口纵向研究，以确定潜在有效的治疗方法，以推进临床试验。在这一竞争性更新中，我们建议确定以下中老年暴露或活动与老年痴呆的神经病理、结构和生化特征之间的关系：心脏保护性剂量的阿司匹林，女性的激素替代疗法，两类具有神经保护作用的降压药(钙通道阻滞剂和血管紧张素转换酶抑制剂)，以及体育锻炼水平。这些观察数据将提供一个独特的视角，了解哪些常用的处方药或运动抑制了特定的疾病机制，从而指导对比较有效性的研究，并帮助选择RCT中要追求的方案。