Alzheimer's Disease: Potential Benefit of Isoflavones

描述（由申请人提供）：候选人：我的目标是成为一名独立的临床研究者，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个独立的研究事业，特别是植物雌激素（大豆雌激素）干预。 有了这个K23奖，我将把100%的时间投入到一个职业计划中，该计划包括来自精通临床研究和指导的个人委员会的指导;通过威斯康星州大学（UW）临床研究者预备计划的正式课程（CIPP; NIH K30），顶点证书，医学教育，发展和领导计划;正式实习;以及研讨会、讲座和讲习班。有了这个职业计划，我将在以前的培训基础上，在研究设计，伦理/负责任的研究行为，数据管理和营养科学方面建立坚实的科学背景。 工作环境：UW医学院是一个首屈一指的研究机构，拥有悠久的成功指导历史，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确定为五大发展领域之二。为了实现这一目标，医学系聘请桑杰·阿斯塔纳（Sanjay Asthana）领导老年医学科。随着我的主要导师Asthana博士的到来，这个机构现在有一个AD研究项目，有14项资助的研究，而且声誉越来越高。我可以利用的其他资源包括一般临床研究中心（GCRC）和VA老年，教育和临床中心（GRECC）。 研究：这项调查研究了大豆异黄酮（一类植物雌激素）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，最近的研究结果引起了人们对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。大豆异黄酮可作为传统HRT的急需替代疗法。少数人类研究项目已经检查了大豆异黄酮的神经认知作用，为异黄酮对认知的有益作用提供了有趣但初步的支持。目前，还没有关于阿托伐他汀治疗AD相关认知功能下降的有效性的数据。60例AD老年患者将入组这项随机、安慰剂对照、双盲、平行组设计的临床研究。受试者将接受100 mg/天的大豆异黄酮或安慰剂治疗6个月。将在基线和开始研究药物治疗后1、3和6个月以及治疗终止后3个月收集认知数据。此外，将分析每次治疗访视时采集的血液中的血浆TNF水平和其他感兴趣的神经内分泌标志物。

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.