Alzheimer's Disease: Potential Benefit of Isoflavones

描述(申请人提供)：应聘者：我的目标是成为一名独立的临床调查员，专门从事治疗和预防策略领域，针对与阿尔茨海默病(AD)相关的神经认知症状。我的短期目标是发展一项独立的研究事业，特别是在植物雌激素(大豆异黄酮)干预方面。 有了这个K23奖项，我将把100%的时间投入到一个职业项目中，其中包括来自精通临床研究和指导的个人委员会的指导；通过威斯康星大学(UW)临床研究人员预备项目(CIPP；NIH K30)、Capstone证书和医学教育、发展和领导力项目进行的正式课程；正式实习；以及研讨会、讲座和研讨会。通过这份职业规划，我将在之前培训的基础上，在研究设计、伦理/负责任的研究行为、数据管理和异黄酮类营养科学方面发展坚实的科学背景。 环境：威斯康星大学医学院是一家顶尖的研究机构，有着悠久的成功导师历史，以及完善的职业发展计划(CIPP)。华盛顿大学最近将神经科学和老年医学列为五大发展领域中的两个。为此，医学部聘请桑杰·阿萨纳担任老年病科主任。随着我的主要导师阿萨纳博士的到来，这家机构现在有了一个拥有14项资助研究的AD研究项目，并获得了越来越高的声誉。我可以利用的其他资源包括综合临床研究中心(GCRC)和退伍军人事务部老年、教育和临床中心(GRECC)。 研究：这项调查考察了大豆异黄酮类植物雌激素对老年AD患者的认知影响。妇女健康倡议(WHI)是一项利用传统激素替代疗法(HRT)的大型试验，最近的研究结果引发了人们对HRT可行性的担忧，因为严重不良反应的风险增加，包括认知能力下降。大豆异黄酮类药物可作为传统激素替代疗法急需的替代疗法。少数几个研究大豆异黄酮对神经认知影响的人类研究项目，为大豆异黄酮对认知的有益作用提供了耐人寻味但又初步的支持。目前，还没有关于异黄酮类药物治疗阿尔茨海默病相关认知功能衰退的有效性的数据。60名老年AD患者将参加这项随机、安慰剂对照、双盲、平行分组设计的临床研究。受试者每天服用100毫克大豆异黄酮片或服用安慰剂，为期6个月。认知数据将在基线、研究药物开始后的1个月、3个月和6个月收集，并在治疗结束后3个月再次收集。此外，每次治疗时采集的血液将被检测血浆异黄酮水平和其他感兴趣的神经内分泌标记物。

DESCRIPTION (provided by applicant): Candidate: My goal is to become an independent clinical investigator, specializing in the area of therapeutic and preventive strategies, targeting the neurocognitive symptoms associated with Alzheimer's disease (AD). My short-term goal is to develop an independent research career focused on phytoestrogen (soy isoflavone) interventions in particular. With this K23 award, I will dedicate 100% of my time to a career program incorporating mentorship from a committee of individuals well-versed in clinical research and mentoring; formal coursework through the University of Wisconsin's (UW) Clinical Investigator Preparatory Program (CIPP; NIH K30), the Capstone Certificate, and the Medical Education, Development, and Leadership program; formal internships; as well as seminars, lectures, and workshops. With this career plan, I will build on previous training, developing a solid scientific background in study design, ethics/responsible conduct of research, data management, and nutritional sciences of isoflavones. Environment: The UW Medical School is a premier research institution with a long history of successful mentorship, and a well-established career development program (CIPP). The UW recently identified Neuroscience and Geriatrics as two of the top five areas of development. Toward this goal, the Department of Medicine recruited Sanjay Asthana to head the Section of Geriatrics. With the arrival of Dr. Asthana, my primary mentor, this institution now has an AD research program with 14 funded investigations, and a growing reputation. Other resources I can avail upon include the General Clinical Research Center (GCRC), and the VA Geriatric, Educational and Clinical Center (GRECC). Research: This investigation examines the cognitive effects of soy isoflavones, a class of phytoestrogens, in older adults with AD. Recent findings from the Women's Health Initiative (WHI), a large trial utilizing traditional hormone replacement therapies (HRTs), have raised concerns over the feasibility of HRTs, given the increased risk of serious adverse effects, including cognitive decline. Soy isoflavones may serve as a critically-needed alternative therapy to traditional HRT. The few human research projects that have examined the neurocognitive effects of soy isoflavones offer intriguing but preliminary support for isoflavones' beneficial actions on cognition. Presently, there are no data regarding the effectiveness of isoflavones to treat AD-associated cognitive declines. Sixty older adults with AD will be enrolled in this randomized, placebo-controlled, double-blind, parallel-group design clinical study. Subjects will receive either 100mg/day of soy isoflavones or a placebo for 6 months. Cognitive data will be collected at Baseline and at 1, 3 and 6 months, post-initiation of study medications, and again 3 months after termination of treatment. In addition, blood, collected at each treatment visit, will be assayed for plasma isoflavone levels, and other neuroendocrine markers of interest.