AGE-RELATED STRUCTURAL AND FUNCTIONAL NEURAL CHANGES ON COGNITIVE MEASURES

描述（由申请人提供）：这是一个指导研究科学家发展奖（K 01）的申请。拟议项目的目标是为申请人提供所需的先进技能，以建立一个独立的认知老化研究计划，使用综合多模态神经成像方法来了解与年龄相关的认知变化。申请人提出了一个全面的培训计划，该计划将教学指导与既定的研究人员相结合;正式的课程;参加哥伦比亚大学正在进行的研讨会;进行前瞻性研究和与个人顾问的应用培训经验。具体的培训目标包括获得认知老化的神经生物学机制方面的先进知识和技能：老化如何影响工作记忆的认知测试和认知测量（如记忆，处理速度和流体能力）的表现。该培训计划将与正在进行的NIA支持的衰老认知、学习和记忆成像研究（5 R 01 AG 026158）协调执行，其主要目标是探索当任务难度操作挑战性能时功能网络募集的变化。这项研究并没有说明基础结构和静息血流模式如何影响年龄组的功能或认知差异。因此，我建议的研究将调查与年龄相关的灰质体积，静息脑血流量和功能活动之间的相互关系。本研究的目的是评估静息血流量和灰质体积是否是功能重组的独立或伴随预测因子，并确定这些指标的变化如何介导年龄和认知之间的关系。因此，拟议的项目目标将阐明与衰老相关的神经生物学变化的多种措施之间的相互关系，并将作为申请人建立一个独立的研究者职业生涯，在老龄化人群中进行多模态神经影像学研究的桥梁。 公共卫生相关性：目前，许多方法（功能或结构神经成像，行为或神经心理学测试）老化研究是独立进行的，从而减少了它们对理解正常老化对大脑的整体影响的影响。目前的研究计划整合了神经活动（功能激活）和潜在大脑结构（脑血流量和脑组织体积）的测量，以研究它们对年龄增长和认知测试表现下降之间关系的影响。

DESCRIPTION (provided by applicant): This is an application for a Mentored Research Scientist Development Award (K01). The goal of the proposed project is to provide the Applicant with the advanced skills needed to establish an independent program of research in cognitive aging using an integrative multi-modal neuroimaging approach to understanding age-related cognitive changes. The Applicant proposes a comprehensive training plan which combines didactic instruction with established researchers; formal coursework; participation in ongoing seminars at Columbia University; conduction of a prospective study and applied training experiences with individual advisors. Specific training goals include acquiring advanced knowledge and skill in the neurobiological mechanisms of cognitive aging: how aging impacts performance on cognitive tests of working memory and measures of cognition such as memory, processing speed and fluid ability. The training plan will be executed in coordination with an ongoing NIA-supported imaging study of cognition, learning and memory in aging (5R01AG026158) whose main goal is to explore changes in functional network recruitment when performance is challenged by task difficulty manipulation. This study does not address how underlying structural and resting blood flow patterns influence age-group functional or cognitive differences. Consequently, the study I am proposing will investigate the interrelations between age-related gray matter volume, resting cerebral blood flow, and functional activity. The goal of this study will be to assess whether resting blood flow and gray matter volume are independent or concomitant predictors of functional reorganization and to determine how changes in these measures mediate the relationship between age and cognition. The proposed project aims will therefore elucidate the interrelationships between multiple measures of neurobiological changes associated with aging and will serve as a bridge for the Applicant to establish an independent investigator career in conducting multi-modal neuroimaging studies in aging populations. PUBLIC HEALTH RELEVANCE: Currently, many approaches (functional or structural neuroimaging, behavioral or neuropsychological testing) to aging research are performed independently thus diminishing their impact on understanding the overall effects of normal aging on the brain. The current research proposal integrates measures of neural activity (functional activations) and underlying brain structure (cerebral blood flow and brain tissue volume) to study their influences on the relationship between advancing age and decreased performance on cognitive tests.