Cognitive and Neural Correlates of Inflammation in Healthy Older Adults

健康老年人炎症的认知和神经相关性

• 批准号: 8529440
• 负责人: Brianne Magouirk Bettcher
• 金额: $ 14.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8529440
• 关键词: Acute-Phase Proteins; Address; Aging; Animal Model; Basic Science; Behavioral; Biological Markers; Biometry; Brain; California; Clinical; Clinical Research; Cognition; Cognitive; Cognitive aging; Communities; Data; Dementia; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Early treatment; Elderly; Evaluation; Exposure to; Fiber; Fostering; Foundations; Functional disorder; Future; Glean; Goals; Growth Factor; Human; Image Analysis; Imaging Techniques; Immune; Immune System Diseases; Immunologist; Immunology; Impaired cognition; Individual; Inflammation; Inflammatory; Interleukin-1; Interleukin-6; International; Intervention; Knowledge; Laboratories; Long-Term Potentiation; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Mediating; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Metric; Modeling; Neurodegenerative Disorders; Neurologist; Neurology; Neuropsychology; Outcome; Parietal; Process; Progranulin; Proteins; Regulation; Research; Research Infrastructure; Research Personnel; Risk; Risk Factors; Role; San Francisco; Staging; Statistical Methods; Structure; System; TNF gene; Temporal Lobe; Training; Translating; Tumor Necrosis Factor-alpha; Universities; Vascular Permeabilities; Work; base; career; cognitive function; cognitive neuroscience; cohort; cytokine; executive function; gray matter; healthy aging; immune function; indexing; inflammatory marker; innovation; insight; modifiable risk; neuroimaging; neuromechanism; neuropsychological; novel; pathological aging; patient oriented; peripheral blood; processing speed; programs; public health relevance; relating to nervous system; research study; skills; white matter

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Brianne Bettcher, a neuropsychology fellow at the University of California, San Francisco Memory and Aging Center (MAC). Dr. Bettcher is establishing herself as a young investigator who conducts patient-oriented clinical research on the role of inflammation in cognitive aging. This K23 award will provide Dr. Bettcher with the support necessary to accomplish the following goals: (1) to garner expertise in the cognitive neuroscience of aging; 2) to advance her knowledge of the immunological contributions to healthy and pathological aging by translating innovative findings from basic science; (3) to acquire proficiency in structural and diffusion neuroimaging; (4) to develop proficiency in advanced statistical methods; and (5) to develop an independent research career. To achieve these goals, Dr. Bettcher has assembled a mentoring team that includes one primary mentor: Dr. Kramer (a clinical neuropsychologist and international leader in the cognitive neuroscience of aging); three co-mentors: Drs. Kristine Yaffe (a neurologist with expertise in immunological biomarkers and biostatistics), Maria Luisa Gorno-Tempini (a neurologist with expertise in structural MRI, specifically diffusion tensor imaging analyses), and Bruce Miller (a neurologist with expertise in behavioral neurology and clinical research); and one consultant: Dr. Tony Wyss-Coray (an immunologist with basic science expertise in inflammation). The proposed research study focuses on the cognitive and neural correlates of inflammation in healthy older adults. Dr. Bettcher will use laboratory indices of inflammation to assess the association between inflammation and cognitive functions, specifically memory consolidation, executive functions, and processing speed (Aim 1). Dr. Bettcher will employ structural and diffusion neuroimaging data to explicate the neural correlates of inflammation, and further identify whether these neural systems mediate the relation between inflammation and cognition (Aim 2). In order to isolate a novel mechanism of immune dysfunction, Dr. Bettcher will also examine the role of an upstream regulator of inflammation (i.e. progranulin) in cognitive functions and its association with brain structure (Aim 3). The proposed research will utilize the existing infrastructure of the MAC to investigate this new program of study. Public health relevance: The results from this study will provide integral information regarding the relationship between inflammation, cognition and brain structure in healthy older adults, and inform the cognitive neuroscience of healthy versus pathological aging. Dr. Bettcher's K23 training will prepare her to conduct multimodal studies of cognitive aging and implement future longitudinal studies that investigate modifiable risk factors for cognitive decline.

描述(由申请人提供)：这是为加州大学旧金山记忆和衰老中心(MAC)的神经心理学研究员Brianne Bettcher博士申请K23奖项。贝彻博士正在确立自己作为一名年轻研究员的地位，她以患者为导向，对炎症在认知老化中的作用进行了临床研究。这一K23奖项将为Bettcher博士提供必要的支持，以实现以下目标：(1)获得衰老认知神经科学方面的专业知识；(2)通过翻译基础科学的创新发现，提高她对免疫学对健康和病理性衰老的贡献的知识；(3)熟练掌握结构和扩散神经成像；(4)熟练掌握先进的统计方法；以及(5)发展独立的研究事业。为了实现这些目标，贝彻博士组建了一支导师团队，其中包括一名主要导师：克莱默博士(Kramer博士，临床神经心理学家和衰老认知神经科学的国际领导者)；三名共同导师：Kristine Yaffe博士(在免疫生物标记物和生物统计学方面有专长的神经学家)，Maria Luisa Gorno-Tempini博士(在结构磁共振方面，特别是扩散张量成像分析方面有专长的神经学家)和Bruce Miller(神经学家，在行为神经学和临床研究方面有专长)；以及一名顾问：Tony Wyss-Coray博士(在炎症方面具有基础科学专长的免疫学家)。这项拟议的研究重点是健康老年人中炎症的认知和神经相关性。Bettcher博士将使用实验室的炎症指数来评估炎症和认知功能之间的联系，特别是记忆巩固、执行功能和处理速度(目标1)。Bettcher博士将使用结构和扩散神经成像数据来解释炎症的神经关联，并进一步确定这些神经系统是否在炎症和认知之间的关系中起中介作用(目标2)。为了分离免疫功能障碍的新机制，Bettcher博士还将研究上游炎症调节因子(即原颗粒蛋白)在认知功能中的作用及其与大脑结构的关联(目标3)。拟议的研究将利用MAC的现有基础设施来调查这一新的研究计划。公共卫生相关性：这项研究的结果将提供关于健康老年人炎症、认知和脑结构之间关系的完整信息，并为健康衰老与病理性衰老的认知神经科学提供信息。贝彻博士的K23培训将为她进行认知老化的多模式研究做好准备，并实施未来的纵向研究，调查认知能力下降的可改变的风险因素。