Recollection and Familiarity in Amnestic-Mild Cognitive Impairment

描述（由申请人提供）：本项目的目标是更好地定义遗忘型轻度认知障碍（a-MCI）患者记忆丧失的具体性质，这是一组富含早期阿尔茨海默病（AD）病理学患者的患者。这项工作将有助于区分记忆丧失由于AD病理与老化。记忆的双过程模型认为，再认是由回忆和熟悉。两者都是受损的早期AD，而只有回忆是受老化。关于a-MCI中这些过程的完整性知之甚少。因此，将在健康老年受试者和患有a-MCI和轻度AD的患者中通过行为手段测量回忆和熟悉度。然后，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叶结构，因此假设行为、ERP和MRI测量将反映该区域在a-MCI中的参与，并在纵向评估中预测向AD的转化。具体而言，熟悉性，一种形式的记忆认为依赖于嗅周皮层，预计将受损的a-MCI相对于老年对照。此外，ERP相关的回忆将不同之间的健康老龄化和a-MCI/AD，反映前额叶功能障碍在前者和海马/内嗅病理在后者。记忆和熟悉的体积MRI和ERP的行为估计的关系将提供进一步了解这些过程的解剖和电生理基础和早期AD病理对他们的影响。此职业发展奖申请的培训计划将建立在候选人先前使用行为和ERP技术研究AD记忆的基础上。除了提高这些技能，候选人将学习一种新的查询模式，定量结构MRI。这种多模式方法的培训将使候选人在成为独立调查员时能够以新颖和灵活的方式处理科学问题。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至40年内将急剧增长。损伤最小的患者可能从潜在的疾病改善干预中获益最多。因此，如本文所建议的，寻求早期诊断工具至关重要。

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.