Associative Memory and Transitive Inference in Aging and Preclinical AD

描述（由申请人提供）：在“正常”衰老过程中，经常报告情节性记忆衰退，但经常引起对早期阿尔茨海默病（AD）的关注。了解AD病理生理过程早期记忆衰退的神经基础对于促进早期诊断、跟踪疾病进展和评估潜在治疗的疗效至关重要。功能性神经影像学已经显示出年轻人，正常老年人和AD痴呆患者在情景记忆任务，特别是联想记忆中的显着差异。最近，我的赞助商的团队发现了临床正常的老年人早期功能和行为改变的证据，这些老年人患有阿尔茨海默病（例如淀粉样蛋白沉积），这表明这些人可能处于AD的临床前阶段。临床前AD记忆功能障碍的神经基础仍有待更充分地阐明，特别是淀粉样蛋白对海马功能的影响。本项目的总体目标是开发一种新的功能磁共振成像范例，结合面孔名称和面孔职业对的关联和传递记忆来探测海马功能，这可能有助于更好地从临床前AD的早期阶段消除“正常”衰老过程的歧义。这种结合将更好地描述情景记忆的神经基础。该实验设计利用了两个关键思想：（1）面孔-姓名对的联想记忆对衰老效应敏感，而面部占用缺陷可能指示淀粉样蛋白相关功能障碍;（2）传递记忆的损伤将是AD相关病理学的更特异性标志物，并且受年龄的影响较小。第一个具体的目的是验证，神经成像任务的特点之间的关联和传递记忆的年轻人的神经差异。第二个具体目标是通过比较年轻人和老年人，评估在PiB-PET淀粉样蛋白成像上没有淀粉样蛋白沉积证据的情况下，关联记忆和/或传递记忆的情景记忆的神经基础是否存在“正常”衰老相关的变化。第三个具体目标是通过比较有和没有任何淀粉样蛋白沉积的个体来评估关联记忆和/或传递记忆的情景记忆的神经基础中是否存在淀粉样蛋白依赖性变化。拟议的项目应有助于我们进一步了解在“正常”衰老过程中情景记忆的神经机制，以及可能代表AD临床前阶段的记忆功能的改变。

DESCRIPTION (provided by applicant): Episodic memory decline is commonly reported in the course of "normal" aging but often raises concern about incipient Alzheimer's disease (AD). Understanding the neural basis for memory decline early in the AD pathophysiological process is critical to facilitate earlier diagnosis, track disease progression and to evaluate the efficacyof potential therapies. Functional neuroimaging has already shown significant differences between young adults, normal elderly and patients with AD dementia in episodic memory tasks, particularly associative memory. More recently, my sponsor's group has found evidence of early functional and behavioral alterations in clinically normal older individuals with Alzheimer's pathology (e.g. amyloid-¿ deposition) that suggest these individuals may be in the preclinical stages of AD. The neural underpinnings of memory dysfunction in preclinical AD remain to be more fully elucidated, particularly the influence of amyloid-¿ on hippocampal function. The overall objective of this project to develop a novel fMRI paradigm that combines associative and transitive memory of face-name and face-occupation pairs to probe hippocampal function, and that may serve to better disambiguate the process of "normal" aging from the early stages of preclinical AD. This combination will better characterize the neural basis of episodic memory. This experimental design leverages two key ideas: (1) associative memory for face-name pairs is sensitive to aging effects, while face-occupation deficits may be indicative of amyloid-¿ related dysfunction; and (2) impairment of transitive memory will be a more specific marker of AD related pathology, and will be less affected by age. The first specific aim is to validate that the neuroimaging task characterizes the neural differences between associative and transitive memory in young adults. The second specific aim assesses whether there are "normal" aging-related changes in the neural basis of episodic memory for associative memory and/or transitive memory by comparing young adults to older adults without evidence of amyloid-¿ deposition on PiB-PET amyloid imaging. The third specific aim is to assess whether there are amyloid-dependent changes in the neural basis of episodic memory for associative memory and/or transitive memory by comparing individuals with and without any amyloid-¿ deposition. The proposed project should serve to further our understanding of the neural mechanisms underlying episodic memory in the process of "normal" aging and the alterations in memory function that may represent preclinical stages of AD.