The Impact of Risk for AD and CVD on Brain Structure and Cognition

本申请为指导的以患者为导向的研究职业发展奖（K23）旨在为候选人提供建立衰老和痴呆风险认知神经科学研究独立计划所需的高级技能。候选人提出一个五年的综合培训计划，将高级技能培训，教学法和正式指导与导师和顾问团队相结合。具体的培训目标包括扩大现有的技能组合和发展以下领域的专门知识：1）新颖的结构神经成像方法，2）认知神经科学研究的理论和应用方面，特别是当它们与认知老化和痴呆风险相关时，和3）这些方法的整合，以更好地了解在特定风险的背景下，大脑结构和功能之间的关系痴呆的因素。导师团队，其中包括具有认知神经心理学，神经影像学，实验心理学，认知老化，痴呆症和流行病学专业知识的个人，再加上布里格姆妇女医院，VA波士顿医疗保健系统和Athinoula A的培训环境。Martinos生物医学成像中心将确保在这三个领域的一流教学。拟议的研究项目将整合先进的灰质形态测量方法，白色物质（WM）微观结构的新型扩散张量成像（DTI）测量方法，以及神经心理学测试，以更好地了解痴呆风险因素对结构和功能的影响。该项目有三个具体目标，包括：1）确定潜在灰质完整性，认知和AD和CVD风险因素之间的关联，2）确定WM微结构完整性，认知和风险因素之间的关联，以及3）纵向检查这些关系。这些数据将进一步阐明与风险因素相关的神经解剖学和神经心理学特征，并将提供有关结构-功能关系的独特信息，这些关系可能在临床疾病过程开始之前很久就存在。总的来说，本申请中描述的职业培训和研究部分将使候选人成为一名独立的研究人员，对衰老和认知能力下降的风险进行神经解剖学和神经心理学研究。

DESCRIPTION (provided by applicant): This application for a Mentored Patient-Oriented Research Career Development Award (K23) is designed to provide the candidate with advanced skills needed to establish an independent program of research in the cognitive neuroscience of aging and dementia risk. The candidate proposes a five-year comprehensive training plan that combines advanced skill training, didactics, and formal instruction with a team of mentors and advisors. Specific training goals include expanding established skill sets and in developing expertise in the following areas: 1) novel structural neuroimaging methodologies, 2) theoretical and applied aspects of cognitive neuroscience research, specifically as they relate to cognitive aging and dementia risk, and 3) the integration of these methodologies to better understand the relationship between brain structure and function in the context of specific risk factors for dementia. The Mentorship team, which includes individuals with expertise in cognitive neuropsychology, neuroimaging, experimental psychology, cognitive aging, dementia and epidemiology, coupled with the training environments of Brigham and Women's Hospital, the VA Boston Healthcare System, and the Athinoula A. Martinos Center for Biomedical Imaging will ensure superb instruction in these three areas. The proposed research project will integrate advanced methods of morphological measurement of gray matter, novel diffusion tensor imaging (DTI) measures of white matter (WM) microstructure, and neuropsychological testing to better understand the impact of dementia risk factors on structure and function. The project has three specific aims, including: 1) determining the association among the integrity of underlying gray matter, cognition, and risk factors for AD and CVD, 2) determining the association among the integrity of WM microstructure, cognition, and risk factors, and 3) examining these relationships longitudinally. These data will further elucidate the neuroanatomical and neuropsychological characteristics associated with risk factors and will provide unique information regarding structure-function relationships that may exist long before a clinical disease process begins. Collectively, the career training and research components described in this application will allow the candidate to emerge as an independent investigator conducting neuroanatomical and neuropsychological studies of aging and risk for cognitive decline.