Vascular Risk Factors in Alzheimer's Disease

描述(由申请人提供)：应聘者计划/培训：应聘者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病学家，在痴呆症、血管风险因素和临床流行病学之间架起桥梁。培训将包括脂类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以及在密切监督下完成研究计划来加强候选人以前的流行病学培训。 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、临床痴呆症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患痴呆症的风险，特别是在晚年患上阿尔茨海默病。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，可能会降低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，而他汀类药物的使用会降低这种风险。 为了解决这些假设，特定的目标1将确定他汀类药物的使用是否降低了AD和/或VAD的风险，以及这些影响是否被载脂蛋白Ee4等位基因的存在所改变。我们还调查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；我们还将在诊断AD和/或VAD之前调查血压变化。一组2581名初步认知正常的老年人的前瞻性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洞察力，从而为开发新的预防和治疗策略提供更多信息。 这项研究计划，连同建议的说教和指导指导，将为候选人进行科学严谨、独立资助、以患者为导向的研究提供必要的职业发展。

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.