Vascular Risk Factors in Alzheimer's Disease

阿尔茨海默病的血管危险因素

• 批准号: 6651014
• 负责人: Gail Li
• 金额: $ 12.51万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651014
• 关键词: Alzheimer's disease; HMG coA reductases; apolipoprotein E; blood pressure; clinical research; dementia; disease /disorder proneness /risk; enzyme inhibitors; genetic susceptibility; genotype; high density lipoproteins; human old age (65+); human subject; hypercholesterolemia; hypertension; longitudinal human study; low density lipoprotein; mental disorder prevention; mental health epidemiology; neuropharmacology; neuropsychological tests; pathologic process; patient oriented research; pharmacogenetics; postdoctoral investigator

DESCRIPTION (provided by applicant): Candidate's Plan/Training: The Candidate plans a career as a patient-oriented clinical research investigator and academic geriatric psychiatrist bridging dementia, vascular risk factors and clinical epidemiology. Training will include formal didactics in lipid metabolism and augmentation of the Candidate's previous epidemiology training with additional advanced biostatistics and epidemiology courses and closely supervised completion of the research plan. Environment: The University of Washington Alzheimer's Disease Patient Registry (ADPR)/Adult Changes in Thought (ACT) and Alzheimer's Disease Research Center (ADRC) provide expertise in epidemiology, clinical dementia evaluation, and biostatistics to form an ideal research environment for epidemiological investigation of Alzheimer's disease (AD) and related dementias. Research: Recent studies suggest mid-life hypercholesterolemia and hypertension increase risk of dementia and specifically AD in late life. Cholesterol-lowering medications, the 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors, i.e., statins, may reduce the risk of AD. We hypothesize that vascular risk factors increase the risk of AD and/or vascular dementia (VaD) and use of statins reduces this risk. To address these hypotheses, Specific Aim 1 will determine whether the use of statins decreases the risk of AD and/or VaD, and whether these effects are modified by the presence of the Apolipoprotein Ee4 allele. We also investigate whether high serum low-density lipoprotein (LDL) and low serum high-density lipoprotein (HDL) are associated with increased risk for AD and/or VaD. Specific Aim 2 will determine if hypertension in older age (> 65 years) increases the risk of AD and/or VaD; we will also investigate blood pressure changes prior to the diagnosis of AD and/or VaD. A prospectively enrolled community-based cohort of 2581 initially cognitively normal elderly will provide the framework for this study. Results from the research project will provide insights into vascular risk factors for AD, thus providing additional information toward development of new prevention and treatment strategies. This research plan, together with the didactic and mentored instruction proposed, will provide the career development necessary for the candidate to conduct scientifically rigorous, independently funded, patient-oriented research.

描述（由申请人提供）：候选人的计划/培训：候选人计划作为一个以病人为导向的临床研究调查员和学术老年精神病学家桥接痴呆症，血管危险因素和临床流行病学的职业生涯。培训将包括脂质代谢方面的正式教学法，并通过额外的高级生物统计学和流行病学课程加强候选人以前的流行病学培训，并密切监督研究计划的完成。 工作环境：华盛顿大学阿尔茨海默病患者登记处（ADPR）/成人思维变化（ACT）和阿尔茨海默病研究中心（ADRC）提供流行病学，临床痴呆评估和生物统计学方面的专业知识，为阿尔茨海默病（AD）和相关痴呆的流行病学调查提供理想的研究环境。研究：最近的研究表明，中年高胆固醇血症和高血压会增加老年痴呆症的风险，特别是老年痴呆症。 降胆固醇药物，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，即，他汀类药物可以降低AD的风险。我们假设血管危险因素增加AD和/或血管性痴呆（VaD）的风险，使用他汀类药物降低了这种风险。 为了解决这些假设，具体目标1将确定使用他汀类药物是否降低AD和/或VaD的风险，以及这些效应是否因载脂蛋白Ee 4等位基因的存在而改变。我们还研究了高血清低密度脂蛋白（LDL）和低血清高密度脂蛋白（HDL）是否与AD和/或VaD风险增加相关。 具体目标2将确定老年人（> 65岁）的高血压是否会增加AD和/或VaD的风险;我们还将研究AD和/或VaD诊断前的血压变化。一个前瞻性招募的2581名最初认知正常的老年人的社区队列将为这项研究提供框架。该研究项目的结果将为AD的血管危险因素提供深入了解，从而为开发新的预防和治疗策略提供额外的信息。 这个研究计划，连同教学和指导教学建议，将提供必要的候选人进行科学严谨，独立资助，以病人为导向的研究职业发展。