Recollection and Familiarity in Amnestic-Mild Cognitive Impairment

描述（由申请人提供）：该项目的目的是更好地定义遗忘性轻度认知障碍（a- mci）患者记忆丧失的具体性质，这一群体富含早期阿尔茨海默病（AD）病理患者。这项工作将有助于区分AD病理引起的记忆丧失与衰老引起的记忆丧失。记忆的双过程模型认为，认知是由回忆和熟悉度提供的。两者都因早期阿尔茨海默病而受损，而只有回忆受到年龄的影响。对于a-MCI中这些过程的完整性知之甚少。因此，在健康老年受试者和a-MCI合并轻度AD患者中，回忆和熟悉度将通过行为手段进行测量。这些估计将与(1)这些过程的事件相关电位（ERP）相关以及(2)使用定量MRI技术的内侧颞叶和皮质体积相关。由于AD的最早病理涉及内侧颞结构，因此假设行为、ERP和MRI测量将反映a-MCI中该区域的参与，并在纵向评估中预测AD的转化。具体来说，与老年对照相比，a- mci患者的熟悉性，一种依赖于鼻周皮层的记忆思维形式，预计会受损。此外，回忆的ERP相关在健康衰老和a-MCI/AD之间存在差异，反映了前者的前额叶功能障碍和后者的海马/内嗅病理。回忆的行为估计与熟悉容积MRI和ERP的关系将进一步了解这些过程的解剖和电生理基础以及早期AD病理对它们的影响。本次职业发展奖申请的培训计划将建立在候选人之前使用行为和ERP技术研究AD记忆的工作基础之上。除了提高这些技能外，候选人还将学习一种新的探究方式，定量结构MRI。这种多模态方法的培训将使候选人在成为一名独立研究者时能够以一种新颖而灵活的方式解决科学问题。阿尔茨海默病已经是一个巨大的公共卫生负担，预计在未来30到40年将急剧增长。损伤最小的患者可能从潜在的疾病修饰干预中获益最多。因此，寻求早期诊断的工具，如本文所建议的，是至关重要的。

DESCRIPTION (provided by applicant): The goal of this project is to better define the specific nature of memory loss in patients with Amnestic Mild Cognitive Impairment (a-MCI), a group enriched in patients with early Alzheimer's disease (AD) pathology. This work will aid in discrimination of memory loss due to AD pathology versus that of aging. Dual-process models of memory argue that recognition is subserved by recollection and familiarity. Both are impaired with early AD while only recollection is affected by aging. Little is known about the integrity of these processes in a-MCI. Therefore, recollection and familiarity will be measured by behavioral means in healthy elderly subjects and patients with a-MCI and mild AD. These estimates will then be related to (1) event-related potential (ERP) correlates of these processes and (2) medial temporal and cortical volumes using quantitative MRI techniques. As the earliest pathology of AD involves medial temporal structures, it is hypothesized that behavioral, ERP, and MRI measures will reflect involvement of this region in a-MCI and predict conversion to AD in longitudinal assessment. Specifically, familiarity, a form of memory thought dependent on perirhinal cortex, is expected to be impaired in a-MCI relative to elderly controls. Further, ERP correlates of recollection will differ between healthy aging and a-MCI/AD, reflecting prefrontal dysfunction in the former and hippocampal/entorhinal pathology in the latter. Relation of behavioral estimates of recollection and familiarity with volumetric MRI and ERP will provide further understanding of the anatomic and electrophysiologic bases of these processes and the impact of early AD pathology on them. The training plan for this Career Development Award application will build upon a foundation produced by the candidate's prior work in the study of memory in AD using behavioral and ERP techniques. In addition to enhancing these skills, the candidate will learn a new modality of inquiry, quantitative structural MRI. Training in such a multi-modality approach will allow for the candidate to address scientific questions in a novel and flexible manner as he becomes an independent investigator. Alzheimer's disease is already a tremendous public health burden which is expected to grow dramatically in the next 30 to 40 years. Patients with minimal impairment may benefit the most from potential disease modifying interventions. Thus, the pursuit of tools for early diagnosis, as proposed here, is critical.