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：候选人计划从事以患者为导向的临床研究研究者和学术老年精神病医生的职业生涯。培训将包括脂质代谢方面的形式教学和候选人以前的流行病学培训的增强，并通过其他高级生物统计学和流行病学课程以及密切监督研究计划的培训。 环境：华盛顿大学阿尔茨海默氏病患者登记局（ADPR）/成人思想变化（ACT）和阿尔茨海默氏病研究中心（ADRC）提供了流行病学，临床痴呆评估和生物统计学方面的专业知识，以形成一个理想的研究环境，以用于对阿尔茨海默氏病（ADEMER'S DIEMTIAS）和相关dementias的流行病学研究。研究：最近的研究表明，中年高胆固醇血症和高血压会增加痴呆症的风险，尤其是晚期AD。 降低胆固醇的药物，3-羟基-3-甲基氯丁基糖酶-A还原酶抑制剂，即汀类药物，可能会降低AD的风险。我们假设血管危险因素增加了AD和/或血管性痴呆（VAD）的风险，而使用他汀类药物会降低这种风险。 为了解决这些假设，具体的目标1将确定他汀类药物的使用是否会降低AD和/或VAD的风险，以及这些影响是否通过载脂蛋白EE4等位基因的存在来改变。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的风险增加有关。 具体目标2将确定年龄较大（> 65岁）的高血压是否会增加AD和/或VAD的风险；我们还将在诊断为AD和/或VAD之前研究血压的变化。最初是认知正常老年人的前瞻性招收的2581人群将为这项研究提供框架。研究项目的结果将为AD的血管风险因素提供见解，从而为开发新的预防和治疗策略提供了更多信息。 该研究计划以及提出的教学和指导的指导将为候选人提供科学严格，独立资助的患者研究所必需的职业发展。