Effect of Statins on Pathobiology of Alzheimer's Disease

描述（由申请人提供）：候选人：Carlsson博士的长期目标是成为阿尔茨海默病（AD）及其与血管危险因素关系的独立临床研究者。作为K23奖项的一部分，Carlsson博士将通过获得临床研究设计，生物统计学，认知理论和测试，流行病学和数据管理方面的高级培训，发展以患者为导向的研究职业生涯，通过人口健康科学计划，心理学的UW研究生院系的UW硕士学位，以及临床研究基础的Capstone证书课程。此外，她将通过临床研究者预备途径（CIPP，NIH K30）完成她的培训。她还将获得管理人类受试者研究的伦理和监管问题的高级培训。 工作环境：威斯康星州医学院的大学是一个首屈一指的研究机构，最近已确定老年医学和神经科学作为研究的五大优先领域的两个。除了UW记忆研究计划和老年医学和老年学部分，Carlsson博士将获得拟议的K23奖的以下资源：威斯康星州阿尔茨海默氏症研究所;威斯康星州阿尔茨海默氏症预防登记处;老龄化研究所; VA老年医学研究，教育和临床中心（GRECC）;和一般临床研究中心（GCRC）。研究：鉴于来自流行病学、动物和临床研究的证据表明他汀类药物可能对AD具有预防作用，Dr. Carlsson建议在AD发生风险增加的中年人群中评价辛伐他汀对AD进展的脑脊液（CSF）和血浆标志物、中枢神经系统（CNS）胆固醇代谢和CNS炎症的影响。将从威斯康星州阿尔茨海默病预防登记处招募100名无痴呆症的男性和女性参与一项为期9个月的随机对照试验，评价辛伐他汀80 mg每晚与安慰剂相比对1）CSF淀粉样蛋白β-42（A β 42）水平; 2）CNS胆固醇代谢的血浆标志物;和3）CSF和炎症的血浆标志物的影响。参与者将在基线和9个月随访时进行空腹实验室检查、CSF收集和认知测试。第1、3和6个月的额外访视将评估副作用。还将在3个月随访时重复进行认知测试。将9个月时的结局指标与基线进行比较。将按载脂蛋白E4状态分析结果。

DESCRIPTION (provided by applicant): Candidate: Dr. Carlsson's long-term goal is to become an independent clinical investigator in Alzheimer's disease (AD) and its relationship to vascular risk factors. As part of this K23 award, Dr. Carlsson will develop a career in patient-oriented research by obtaining advanced training in clinical research design, biostatistics, cognitive theory and testing, epidemiology, and data management through the UW Masters of Science in Population Health Sciences Program, the UW Graduate School Department of Psychology, and the Capstone Certificate Program in Fundamentals of Clinical Research. Furthermore, she will complete her training through the Clinical Investigator Preparatory Pathway (CIPP, NIH K30). She will also obtain advanced training in ethical and regulatory issues that govern human subjects research. Environment: The University of Wisconsin Medical School is a premier research institution that has recently identified Geriatrics and Neurosciences as two of the top five priority areas for research. In addition to the UW Memory Research Program and Section of Geriatrics and Gerontology, Dr. Carlsson will have access to the following resources for the proposed K23 award: the Wisconsin Alzheimer's Institute; the Wisconsin Registry for Alzheimer's Prevention; the Institute on Aging; the VA Geriatric Research, Education and Clinical Center (GRECC); and the General Clinical Research Center (GCRC). Research: Given the evidence from epidemiological, animal, and clinical research suggesting that statins may have a preventive role in AD, Dr. Carlsson proposes to evaluate the effect of simvastatin on cerebrospinal fluid (CSF) and plasma markers of AD progression, central nervous system (CNS) cholesterol metabolism, and CNS inflammation in a population of middle-aged adults at increased risk for developing AD. 100 men and women without dementia from the Wisconsin Registry for Alzheimer's Prevention will be recruited for participation in a 9-month randomized, controlled trial evaluating the effects of simvastatin 80 mg nightly vs. placebo on 1) CSF amyloid beta-42 (Abeta42) levels; 2) plasma markers of CNS cholesterol metabolism; and 3) CSF and plasma markers of inflammation. Participants will have fasting labs drawn, CSF collected, and cognitive testing done at baseline and 9-month follow-up. Additional visits at 1, 3, and 6 months will assess side effects. Cognitive testing will also be repeated at the 3-month follow-up. Outcome measures at 9 months will be compared to baseline. Results will be analyzed by apolipoprotein E4 status.