Functional-Anatomic Correlates of Relational Memory in Aging and MCI

描述(申请人提供)：关系记忆--对信息要素之间的关系或联系进行编码和检索--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害。到目前为止，人们对衰老和阿尔茨海默病关系记忆缺陷的认知过程和神经机制知之甚少。在轻度认知障碍(MCI)受试者中，阐明关系记忆缺陷的神经基础将有助于理解AD非常早期阶段正常衰老和病理性衰老之间的差异。对健康年轻人的功能神经成像研究表明，关系记忆是由前额叶(RFC)和内侧颞叶(MIL)介导的。尽管PFC被认为是编码和提取关系信息所必需的策略过程的中介，但MIL被认为在将事件的各种认知、情感和知觉成分捆绑或联系在一起形成完整的记忆痕迹方面发挥着关键作用。最近的数据表明，与年龄相关的关系记忆缺陷可能是由于RFC介导的策略性、受控加工的下降，而与AD相关的关系记忆障碍反映了MIL结合机制的破坏。这项应用的中心目的是阐明在衰老和早期阿尔茨海默病中导致关系记忆损害的核心认知过程和基本神经机制。我们将利用解剖学受限的功能磁共振成像来评估三组人在记忆表现过程中PFC和MIL的激活：年轻人、健康的老年人和符合遗忘性MCI标准的受试者。所提出的实验纳入了认知范式，这些范式直接操纵策略性和约束性过程对关系记忆的贡献，然后检查对功能神经结构的影响。作为拟议的K01应用程序的一部分，候选人寻求以下方面的培训：1)先进的功能磁共振技术，2)临床研究设计，以及3)功能和结构磁共振数据的整合。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.