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

• 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
• 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' s Disease; Alzheimer' s disease pathology; Alzheimer' 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

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.

这项提案要求一次性续签以患者为中心的职业生涯中期调查员奖 研究(K24)。候选人安吉拉·杰斐逊博士是一位神经心理学家，他的跨学科研究 该计划侧重于了解心脑血管完整性对 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学教授，范德比尔特记忆创始主任 &阿尔茨海默氏症中心。自从13年前完成训练以来，杰斐逊博士已经确立了自己的地位 富有成效的临床研究人员，拥有强大的NIH资金和高影响力、多产的出版记录。超过了 在过去的十年里，包括最初的K24资助期(2013-2018)，她展示了强大的 致力于专业教育和指导。此次K24续订将有助于继续 为杰斐逊博士扩大临床研究能力提供有保障的时间。尤其是，她会 扩展她在阿尔茨海默病脑脊液生物标记物方面的专业知识，以包括创新的分子 反映伴随途径的生物标记物，如细胞外基质重塑、小胶质细胞激活和 突触功能障碍。她还将扩大蛋白质组生物标记物的范围，通过利用 最新的基于发现的质谱学方法。这些工具将大大丰富我们的 了解血管健康受损与异常脑老化和 提供预防或延缓与认知障碍相关的病理性级联的策略 痴呆症。此外，拟议的奖励将允许杰斐逊博士继续使用她的研究项目 作为指导早期职业调查人员的平台，包括本科生、研究生和医学生； 博士后研究员；阿尔茨海默氏症认知老化患者导向研究的早期职业教师 疾病和小血管疾病。这项提议整合了杰斐逊博士的跨学科研究团队和 范德比尔特记忆与阿尔茨海默氏症中心和范德比尔特临床研究所提供的资源 和翻译研究，为学员提供丰富的培训环境。培训和研究 在K24机制的推动下，更新不仅将促进对心血管和 阿尔茨海默病发病机制及临床表现的脑血管通路 和小血管疾病，但它也将很好地培养一批下一代认知老化研究人员- 定位于为该领域做出有意义的贡献。