Functional-Anatomic Correlates of Relational Memory in Aging and MCI

描述（由申请人提供）：关系记忆-对信息元素之间的关系或关联进行编码和检索-对年龄增长的影响特别敏感。此外，关系记忆缺陷是阿尔茨海默病（AD）患者最早观察到的一些损伤。迄今为止，认知过程和神经机制背后的关系记忆缺陷在衰老和阿尔茨海默氏症知之甚少。阐明关系记忆缺陷的神经基础将有助于理解轻度认知障碍（MCI）受试者在阿尔茨海默病早期正常和病理性衰老之间的差异。健康年轻人的功能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。虽然PFC被认为是调解编码和检索关系信息所必需的策略过程，但MIL被认为在将事件的各种认知、情感和知觉成分结合或连接到一个综合记忆痕迹中发挥关键作用。最近的数据表明，关系记忆中与年龄相关的缺陷可能是由于rfc介导的战略性、控制性加工的下降，而与ad相关的关系记忆损伤反映了MIL结合机制的破坏。本应用程序的中心目的是阐明核心认知过程和基本的神经机制，导致关系记忆障碍在老年和早期AD。我们将利用解剖受限的功能磁共振成像来评估三组人在记忆表现中的PFC和MIL激活：年轻人、健康老年人和符合遗忘型轻度认知损伤标准的受试者。我们提出的实验包括直接操纵策略和绑定过程对关系记忆的贡献的认知范式，然后检查对功能神经结构的影响。作为K01申请的一部分，候选人寻求以下方面的培训：1)先进的功能MRI技术，2)临床研究设计，以及3)功能和结构MRI数据的整合。该研究计划将培养候选人成为一名独立的科学家，使用认知和神经成像方法研究正常和病理性衰老中记忆缺陷的本质。

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.