Structural-functional MRI Studies of Memory in MCI & AD

描述(由申请者提供)：这是一份K23指导的以患者为导向的研究职业发展奖的申请书，题为“MCI和AD中记忆的结构-功能磁共振研究”。这项拟议研究的主要目标是使用一套完整的结构和功能磁共振测量来确定正常衰老、轻度认知障碍(MCI)和非常轻微的阿尔茨海默病(AD)中潜在的记忆功能障碍的解剖和生理异常。 定量体积磁共振方法能够检测衰老、MCI和AD的神经解剖异常，其中一些有助于预测认知能力的下降。功能磁共振成像(FMRI)工具已经开始揭示与学习和记忆相关的特定大脑区域活动。尽管记忆缺陷是阿尔茨海默病的标志性首发症状，但很少有功能磁共振研究试图探索与衰老、MCI或AD的记忆丧失相关的特定异常，神经退行性结构变化与脑激活模式之间的关系才刚刚开始研究。 因此，这项研究的主要目标是：1)研究年轻人和老年对照组以及MC患者与词汇表编码相关的区域脑激活模式。和非常轻微的阿尔茨海默病，使用与事件相关的“后续记忆”功能磁共振成像范式，以及2)研究这些激活模式和区域脑萎缩之间的关系，使用定量体积磁共振技术测量。本研究的主要假设是，老年人、MCI和AD受试者在词表学习过程中会表现出不同的fMRI异常激活模式，这些异常不仅反映萎缩，而且表明尝试的代偿反应，其中一些将预测随后的回忆，而另一些则不会。 作为拟议研究的一部分，候选人寻求在以下方面进行培训：1)整合结构和功能磁共振数据的功能磁共振技术和方法；2)学习和记忆的认知神经科学，以及与年龄相关的认知下降的心理测量学；以及3)伦理临床研究方法。拟议的研究计划、教学课程以及导师和顾问的辅导指导将促进候选人发展为一名独立的临床医生-科学家，使用神经成像和认知方法来研究衰老、MCI和AD中记忆缺陷的解剖学和生理学。

DESCRIPTION (provided by applicant): This is an application for a K23-Mentored Patient-Oriented Research Career Development Award entitled "Structural-functional MRI studies of memory in MCI & AD." The primary goal of the proposed research is to use an integrated set of structural and functional MRI measures to define the anatomic and physiologic abnormalities underlying memory dysfunction in normal aging, mild cognitive impairment (MCI), and very mild Alzheimer's disease (AD). Quantitative volumetric MRI methods are capable of detecting neuroanatomic abnormalities in aging, MCI and AD some of which are useful as predictors of cognitive decline. Functional MRI (fMRI) tools have begun revealing specific regional brain activity associated with learning and memory. Despite the fact that memory deficits are a hallmark initial symptom of AD, very few fMRi studies have attempted to explore specific abnormalities associated with memory loss in aging, MCI, or AD, and relationships between neurodegenerative structural changes and brain activation patterns are only beginning to be investigated. Therefore, the primary goals of the proposed research are to 1) study regional brain activation patterns associated with encoding of word lists in young and elderly controls, and in patients with MC! and very mild AD, using an event-related "subsequent-memory" fMRI paradigm, and 2) study the relationships between these activation patterns and regional brain atrophy, measured using quantitative volumetric MRI techniques. The overarching hypotheses of this research are that elderly, MCI, and AD subject groups will show different abnormal fMRI activation patterns during word list learning, and that these abnormalities will not merely reflect atrophy but will indicate attempted compensatory responses, some of which will predict subsequent recall and some of which will not. As part of the proposed research, the candidate seeks training in: 1) fMRI techniques and methods for integrating structural and fMRI data; 2) the cognitive neuroscience of learning and memory and psychometrics of age-related cognitive decline; and 3) ethical clinical research methods. The proposed research plan, didactic courses, and tutorial instruction from mentors and advisors will foster the candidate's development into an independent clinician-scientist using neuroimaging and cognitive methods to study the anatomy and physiology of memory deficits in aging, MCI, and AD.