Alzheimer's Disease: Potential Benefit of Isoflavones

阿尔茨海默病：异黄酮的潜在益处

• 批准号: 7472379
• 负责人: CAREY E GLEASON
• 金额: $ 13.85万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7472379
• 关键词: Adverse effects; Affect; Age; Alternative Therapies; Alzheimer' s Disease; American; Apolipoprotein E; Area; Basic Science; Biological Assay; Blood; Bone Density; Class; Clinical; Clinical Investigator; Clinical Research; Cognition; Cognitive; Complementary and alternative medicine; Conjugated Equine Estrogens; Data; Dementia; Development; Disease Progression; Dose; Double-Blind Method; Educational workshop; Effectiveness; Elderly; Enrollment; Environment; Epidemic; Estradiol; Estrogen Therapy; Estrogens; Ethics; Event; Exhibits; Funding; Future; Genotype; Geriatrics; Goals; Head; Healthcare; Hormone replacement therapy; Human; Impaired cognition; Individual; Innovative Therapy; Institution; Internships; Intervention; Investigation; Isoflavones; Leadership; Lipids; Malignant Neoplasms; Manufacturer Name; Medical Education; Medicine; Memory; Mentored Clinical Oncology Award; Mentored Clinical Scientist Award; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Molecular Genetics; Neurobiology; Neurocognitive; Neurosciences; Neurosecretory Systems; Numbers; Other Resources; Patients; Pharmaceutical Preparations; Phytoestrogens; Pilot Projects; Placebo Control; Placebos; Plasma; Population; Postmenopause; Prempro; Prevalence; Prevention strategy; Program Development; Property; Publishing; Randomized; Rate; Recording of previous events; Recruitment Activity; Research; Research Design; Research Project Grants; Risk; Safety; Solid; Symptoms; Therapeutic; Time; Training; United States National Institutes of Health; Universities; Venous; Visit; Wisconsin; Woman; Women' s Health; base; brain tissue; career; cerebrovascular; cognitive function; data management; day; design; interest; lectures; medical schools; men; nutrition; older women; prevent; programs; response; selective attention; soy; soy protein isolate

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.

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，专门研究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独立的研究生涯，特别关注植物雌激素（大豆异黄酮）干预。 凭借这个 K23 奖项，我将把 100% 的时间投入到职业计划中，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) 临床研究者预备计划 (CIPP; NIH K30)、Capstone 证书以及医学教育、发展和领导力计划的正式课程；正式实习；以及研讨会、讲座和讲习班。通过这个职业规划，我将在之前的培训基础上，在异黄酮的研究设计、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。 环境：威斯康星大学医学院是一所一流的研究机构，拥有悠久的成功指导历史和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个最重要发展领域中的两个。为了实现这一目标，医学部聘请桑贾伊·阿萨纳 (Sanjay Asthana) 担任老年科主任。随着我的主要导师 Asthana 博士的到来，该机构现在拥有 AD 研究项目，其中包括 14 项资助的调查，并且声誉不断提高。我可以利用的其他资源包括普通临床研究中心 (GCRC) 和 VA 老年病学、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）对患有 AD 的老年人的认知影响。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，其最新发现引起了人们对 HRT 可行性的担忧，因为严重不良反应（包括认知能力下降）的风险增加。大豆异黄酮可能作为传统激素替代治疗急需的替代疗法。少数研究大豆异黄酮对神经认知作用的人类研究项目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，尚无关于异黄酮治疗 AD 相关认知能力下降有效性的数据。 60 名患有 AD 的老年人将参加这项随机、安慰剂对照、双盲、平行组设计的临床研究。受试者将接受 100 毫克/天的大豆异黄酮或安慰剂，为期 6 个月。将在基线以及开始研究药物后 1、3 和 6 个月以及治疗终止后 3 个月收集认知数据。此外，每次治疗时收集的血液将进行血浆异黄酮水平和其他感兴趣的神经内分泌标记物的检测。

项目成果

An Examination of Brain Abnormalities and Mobility in Individuals with Mild Cognitive Impairment and Alzheimer's Disease.

• DOI: 10.3389/fnagi.2017.00086
• 发表时间: 2017
• 期刊: Frontiers in aging neuroscience
• 影响因子: 4.8
• 作者: Fischer BL;Bacher R;Bendlin BB;Birdsill AC;Ly M;Hoscheidt SM;Chappell RJ;Mahoney JE;Gleason CE
• 通讯作者: Gleason CE

Increased risk for falling associated with subtle cognitive impairment: secondary analysis of a randomized clinical trial.

• DOI: 10.1159/000228257
• 发表时间: 2009
• 期刊: Dementia and geriatric cognitive disorders
• 影响因子: 2.4
• 作者: Gleason CE;Gangnon RE;Fischer BL;Mahoney JE
• 通讯作者: Mahoney JE

Cognitive benefits of hormone therapy: cardiovascular factors and healthy-user bias.

• DOI: 10.1016/j.maturitas.2009.09.014
• 发表时间: 2009-11-20
• 期刊: Maturitas
• 影响因子: 4.9
• 作者: Wharton W;Dowling M;Khosropour CM;Carlsson C;Asthana S;Gleason CE
• 通讯作者: Gleason CE

Awareness of memory abilities in community-dwelling older adults with suspected dementia and mild cognitive impairment.

对疑似痴呆和轻度认知障碍的社区老年人的记忆能力的认识。

• DOI: 10.1159/000318752
• 发表时间: 2010
• 期刊: Dementia and geriatric cognitive disorders
• 影响因子: 2.4
• 作者: Lin,Feng;Wharton,Whitney;Dowling,NMaritza;Ries,MicheleL;Johnson,SterlingC;Carlsson,CynthiaM;Asthana,Sanjay;Gleason,CareyE
• 通讯作者: Gleason,CareyE

Potential role of estrogen in the pathobiology and prevention of Alzheimer's disease.

雌激素在阿尔茨海默病的病理学和预防中的潜在作用。

• 发表时间: 2009
• 期刊: American journal of translational research
• 影响因子: 2.2
• 作者: Wharton,Whitney;Gleason,CareyE;Lorenze,KatelinR;Markgraf,TamaraS;Ries,MicheleL;Carlsson,CynthiaM;Asthana,Sanjay
• 通讯作者: Asthana,Sanjay