Risk factors and prevention targets for abnormal cognitive aging

认知老化异常的危险因素及预防目标

基本信息

批准号：
10542371
负责人：
ANGELA L. JEFFERSON
金额：
$ 17.86万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10542371
关键词：
Academic Medical Centers Acceleration Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Alzheimer’s disease biomarker Amyloid Amyloid beta-42 Amyloid beta-Protein Amyloidosis Aorta Award Biological Markers Blood Vessels Brain Cardiac Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cerebrospinal Fluid Cerebrovascular Circulation Cerebrovascular Disorders Clinical Clinical Research Cognitive Cognitive aging Data Dementia Disease Outcome EFRAC Elderly Environment Extracellular Matrix Functional disorder Funding Funding Opportunities Goals Health Human Impaired cognition Injury Instruction Interdisciplinary Study Investigation Knowledge Light Mass Spectrum Analysis Mediating Medical Students Memory Mentors Mentorship Methods Microcirculation Microglia Microvascular Dysfunction Midcareer Investigator Award in Patient-Oriented Research Molecular Nerve Degeneration Neurofibrillary Tangles Neurology Neuronal Injury Neuropsychology Outcome Pathogenesis Pathologic Pathologic Processes Pathology Pathway interactions Physiologic pulse Play Positioning Attribute Postdoctoral Fellow Predisposing Factor Prevention Prevention strategy Productivity Professional Education Proteomics Public Health Publications Research Research Personnel Research Project Grants Resources Risk Risk Factors Role Scientific Advances and Accomplishments Structure Synapses Technology Thinness Time Training Translational Research United States National Institutes of Health Vascular Diseases Work aging brain axon injury brain abnormalities brain health brain volume career cerebral hemodynamics cerebrovascular cerebrovascular pathology cognitive performance data infrastructure dementia risk early-career faculty glial activation graduate student hemodynamics indexing innovation insight interest molecular marker neurofilament neuroimaging neuroimaging marker next generation novel patient oriented patient oriented research prevent professor programs skills tau Proteins tau-1 therapeutic target tool undergraduate student vascular risk factor white matter

项目摘要

This proposal is requesting a one-time renewal of a Midcareer Investigator Award in Patient-Oriented Research (K24). The candidate, Dr. Angela Jefferson, is a neuropsychologist whose interdisciplinary research program focuses on understanding the impact of cardiovascular and cerebrovascular integrity on the pathogenesis and clinical manifestation of Alzheimer's disease and small vessel disease. Dr. Jefferson is a Professor of Neurology at Vanderbilt University Medical Center and founding Director of the Vanderbilt Memory & Alzheimer's Center. Since completing her training 13 years ago, Dr. Jefferson has established herself as a productive clinical researcher with strong NIH funding and a high-impact, prolific publication record. Over the last decade, including the original K24 funding period (2013-2018), she has demonstrated a strong commitment to professional education and mentorship. This K24 renewal will be instrumental in continuing to provide protected time for Dr. Jefferson to expand her clinical research capabilities. In particular, she will expand her expertise in cerebrospinal fluid biomarkers of Alzheimer's disease to include innovative molecular biomarkers reflecting concomitant pathways, such as extracellular matrix remodeling, microglial activation, and synaptic dysfunction. She will also expand the breadth of proteomic biomarkers at her disposal by leveraging state of the art discovery-based mass spectrometry methods. These tools will substantially enrich our understanding of the mechanisms by which compromised vascular health relates to abnormal brain aging and inform strategies to prevent or delay the pathological cascade associated with cognitive impairment and dementia. Furthermore, the proposed award will allow Dr. Jefferson to continue to use her research program as a platform to mentor early career investigators, including undergraduate, graduate, and medical students; postdoctoral fellows; and early career faculty in patient-oriented research in cognitive aging, Alzheimer's disease, and small vessel disease. This proposal integrates Dr. Jefferson's interdisciplinary research team and resources available through the Vanderbilt Memory & Alzheimer's Center and Vanderbilt Institute for Clinical and Translational Research to offer a rich training environment for mentees. The training and research facilitated by this K24 mechanism renewal will not only advance knowledge regarding cardiovascular and cerebrovascular pathways contributing to the pathogenesis and clinical manifestation of Alzheimer's disease and small vessel disease, but it will also develop a cadre of next-generation cognitive aging researchers well- positioned to make meaningful contributions to the field.

该提案要求一次性续展以患者为中心的职业生涯中期研究者奖研究（K24）。候选人安吉拉·杰斐逊博士是一位神经心理学家，其跨学科研究该计划的重点是了解心血管和脑血管完整性对阿尔茨海默病和小血管病的发病机制和临床表现。杰斐逊博士是一位范德比尔特大学医学中心神经病学教授兼范德比尔特记忆中心创始主任和阿尔茨海默氏症中心。自 13 年前完成培训以来，杰斐逊博士已将自己确立为一名多产的临床研究人员，拥有强大的 NIH 资金和高影响力、多产的发表记录。超过过去十年，包括最初的K24资助期间（2013-2018），她表现出了强大的实力致力于专业教育和指导。 K24 更新将有助于继续为杰斐逊博士提供受保护的时间来扩展她的临床研究能力。特别是，她将扩大她在阿尔茨海默病脑脊液生物标志物方面的专业知识，包括创新分子反映伴随途径的生物标志物，例如细胞外基质重塑、小胶质细胞激活和突触功能障碍。她还将利用现有技术扩大蛋白质组生物标志物的广度最先进的基于发现的质谱方法。这些工具将极大地丰富我们的了解血管健康受损与大脑异常老化相关的机制提供预防或延缓与认知障碍相关的病理级联反应的策略，失智。此外，拟议的奖项将使杰斐逊博士能够继续使用她的研究计划作为指导早期职业研究人员（包括本科生、研究生和医学生）的平台；博士后研究员；和早期职业教师从事以患者为导向的认知衰老、阿尔茨海默病研究病和小血管病。该提案整合了杰斐逊博士的跨学科研究团队和通过范德比尔特记忆与阿尔茨海默病中心和范德比尔特临床研究所提供的资源和转化研究为学员提供丰富的培训环境。培训与研究这种 K24 机制更新所促进的不仅将增进有关心血管和疾病的知识脑血管通路有助于阿尔茨海默病的发病机制和临床表现和小血管疾病，但它也将培养下一代认知衰老研究人员的骨干队伍—— 旨在为该领域做出有意义的贡献。