Assessment of Cholinergic and Cognitive Function Using Pharmacologic ASL-Perfusio

描述（由申请人提供）：这是一份题为“使用药理学ASL灌注MRI评估胆碱能和认知功能”的指导性患者导向职业发展奖（K23）的申请。项目摘要：本研究计划将探讨结合药理学操作和动脉自旋标记灌注MRI（药理学ASL-pMRI）作为胆碱能功能的体内探针的价值。需要研究体内胆碱能功能的方法来更好地理解乙酰胆碱在大脑皮层生理学中的作用，以及在健康和疾病状态下的认知过程中的作用。在本研究中，将使用药理学ASL-pMRI来表征年轻健康受试者对胆碱能操作的正常脑灌注反应。还将获得认知测量结果，并将其与脑灌注变化相关联。然后将使用药理学ASL-pMRI和认知测试来研究胆碱能反应如何随着正常衰老和谵妄而改变。候选人的研究兴趣是药理学神经影像学在衰老和年龄相关疾病中胆碱能功能研究的应用。候选人之前的培训包括神经药理学的基础科学研究，行为神经学的临床培训，以及NINDS赞助的国家研究服务奖下的功能成像和临床研究的初步经验。这项拟议的研究将为候选人提供功能性MRI研究方法，应用，实验设计和分析方面的更高级培训，并将促进候选人发展成为具有药理学MRI独特专业知识的独立研究者。在研究设计，统计学，伦理学和功能成像教学课程将补充研究项目。研究环境包括MRI和临床研究的优秀设施，以及多学科咨询委员会的指导。相关性：该申请的优势包括在研究项目中创新使用药理学ASL-pMRI，咨询委员会的专业知识以及候选人的职业发展潜力。建议的研究项目将阐明胆碱能系统在痴呆和谵妄等常见的年龄相关神经病理状况中的作用。这将反过来导致新的和更有效的治疗策略，这些条件，并有助于改善医疗保健和生活质量，为越来越多的美国老年人。

DESCRIPTION (provided by applicant): This is an application for a Mentored Patient-Oriented Career Development Award (K23) entitled "Assessment of Cholinergic and Cognitive Function Using Pharmacologic ASL-perfusion MRI". Project Summary: This research project will investigate the value of combined pharmacologic manipulation and arterial spin-labeled perfusion MRI (pharmacologic ASL-pMRI) as an in vivo probe of cholinergic function. Methods to investigate cholinergic function in vivo are needed to better understand the role of acetylcholine in the physiology of the cerebral cortex, and in cognitive processes in health and in disease states. In this study, pharmacologic ASL-pMRI will be used to characterize the normal cerebral perfusion response to cholinergic manipulation in young healthy subjects. Cognitive measures will also be obtained and correlated with cerebral perfusion changes. Pharmacologic ASL-pMRI and cognitive testing will then be used to study how the cholinergic response is altered with normal aging and in delirium. The candidate's research interest is the application of pharmacologic neuroimaging to the study of cholinergic function in aging and age-related disease. The candidate's prior training includes basic science research in neuropharmacology, clinical training in behavioral neurology, and initial experience in functional imaging and clinical research under a NINDS-sponsored National Research Service Award. This proposed study will provide the candidate with more advanced training in the methods, applications, experimental design and analysis of functional MRI research, and will foster the candidate's development into an independent investigator with unique expertise in pharmacologic MRI. Didactic coursework in study design, statistics, ethics, and functional imaging will complement the research project. The research environment includes outstanding facilities for MRI and clinical research, and mentoring from a multi-disciplinary advisory committee. Relevance: The strengths of this application include the innovative use of pharmacologic ASL-pMRI in the research project, the expertise of the advisory committee, and the career development potential of the candidate. The proposed research project will elucidate the role of the cholinergic system in the common age-related neuropathologic conditions of dementia and delirium. This will in turn lead to new and more effective treatment strategies for these conditions, and help to improve health care and quality of life for the growing ranks of older Americans.