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. ? ?