Vascular Risk Factors in Alzheimer's Disease

阿尔茨海默病的血管危险因素

• 批准号: 6936466
• 负责人: Gail Li
• 金额: $ 12.53万
• 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/6936466
• 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： 候选人计划成为一名以患者为导向的临床研究调查员和学术老年精神科医生，在痴呆症、血管危险因素和临床流行病学之间架起桥梁。培训将包括脂质代谢方面的正式教学，以及通过额外的高级生物统计学和流行病学课程来增强候选人之前的流行病学培训，并密切监督研究计划的完成。 环境：华盛顿大学阿尔茨海默病患者登记处 (ADPR)/成人思想转变 (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形成理想的研究环境。研究：最近的研究表明，中年高胆固醇血症和高血压会增加晚年患痴呆症，特别是 AD 的风险。 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会增加 AD 和/或血管性痴呆 (VaD) 的风险，而使用他汀类药物可降低这种风险。 为了解决这些假设，具体目标 1 将确定他汀类药物的使用是否会降低 AD 和/或 VaD 的风险，以及载脂蛋白 Ee4 等位基因的存在是否会改变这些效应。我们还研究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 将确定老年高血压（> 65 岁）是否会增加 AD 和/或 VaD 的风险；我们还将在诊断 AD 和/或 VaD 之前调查血压变化。前瞻性招募的 2581 名最初认知正常的老年人群体将为本研究提供框架。该研究项目的结果将深入了解 AD 的血管危险因素，从而为制定新的预防和治疗策略提供更多信息。 该研究计划以及拟议的教学和指导说明将为候选人提供必要的职业发展，以进行科学严谨、独立资助、以患者为导向的研究。