Functional-Anatomic Correlates of Relational Memory in Aging and MCI

描述（由申请人提供）：关系记忆-信息元素之间的关系或关联的编码和检索-对年龄增长的影响特别敏感。此外，关系记忆的缺陷是在阿尔茨海默病（AD）患者中观察到的最早的损伤之一。到目前为止，认知过程和神经机制的关系记忆缺陷的老化和AD知之甚少。阐明关系记忆缺陷的神经基础应被证明是有用的理解正常和病理老化之间的差异在非常早期的AD，在轻度认知障碍（MCI）的主题。对健康年轻人的功能性神经影像学研究表明，关系记忆是由前额叶皮层（RFC）和内侧颞叶（MIL）介导的。前额叶皮层被认为是介导编码和检索关系信息所必需的策略过程，而MIL被认为在将事件的各种认知、情感和感知成分绑定或链接到一个整合的记忆痕迹中起着关键作用。最近的数据表明，年龄相关的赤字关系记忆可能是由于RFC介导的战略，控制处理的下降，而AD相关的关系记忆障碍反映MIL结合机制的中断。本申请的中心目的是阐明核心认知过程和基本神经机制，引起衰老和早期AD的关系记忆障碍。我们将利用解剖学限制的功能磁共振成像评估PFC和MIL激活记忆性能在三组：年轻人，健康的老年人，和受试者谁符合遗忘型MCI的标准。建议的实验纳入认知范式，直接操纵的战略和绑定过程的关系记忆的贡献，然后检查功能神经结构的影响。作为K 01申请的一部分，候选人寻求以下方面的培训：1）先进的功能性MRI技术，2）临床研究设计，3）功能性和结构性MRI数据的整合。拟议的研究计划将促进候选人发展成为一名独立的科学家，使用认知和神经成像方法来研究正常和病理性衰老中记忆缺陷的性质。

DESCRIPTION (provided by applicant): Relational memory - the encoding and retrieval of the relations or associations among informational elements - is particularly sensitive to the effects of advancing age. Furthermore, deficits in relational memory are some of the earliest impairments observed in individuals with Alzheimer's Disease (AD). To date, the cognitive processes and neural mechanisms underlying relational memory deficits in aging and AD are poorly understood. Elucidating the neural bases of relational memory deficits should prove useful in understanding differences between normal and pathological aging at very early stages of AD, in subjects with mild cognitive impairment (MCI). Functional neuroimaging studies of healthy young adults suggest that relational memory is mediated by the prefrontal cortex (RFC) and the medial temporal lobe (MIL). Whereas the PFC is thought to mediate strategic processes necessary to encode and retrieve relational information, the MIL is considered to play a critical role in binding or linking together the various cognitive, affective, and perceptual components of a event into an integrated memory trace. Recent data suggest that age-related deficits in relational memory are likely due to declines in RFC-mediated strategic, controlled processing, whereas AD-related impairments in relational memory reflect disruption of MIL binding mechanisms. The central aim of this application is to elucidate the core cognitive processes and fundamental neural mechanisms that give rise to relational memory impairments in aging and early AD. We will utilize anatomically constrained fMRI to assess PFC and MIL activations during memory performance in three groups: young adults, healthy older adults, and subjects who meet criteria for amnestic MCI. The proposed experiments incorporate cognitive paradigms that directly manipulate the contribution of strategic and binding processes to relational memory and then examine the effect on functional neural architecture. As part of the proposed K01 application, the candidate seeks training in: 1) advanced functional MRI techniques, 2) clinical research design, and 3) integration of functional and structural MRI data. The proposed research plan will foster the candidate's development into an independent scientist, using cognitive and neuroimaging methods to study the nature of memory deficits in normal and pathological aging.