Recollection and Familiarity in Amnestic-Mild Cognitive Impairment

描述(申请人提供)：该项目的目标是更好地确定遗忘性轻度认知障碍(a-MCI)患者记忆丧失的具体性质，这是一组丰富的早期阿尔茨海默病(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所致的记忆丧失。记忆的双加工模型认为，记忆和熟悉性对认知起着辅助作用。两者都在早期阿尔茨海默病中受损，而只有记忆力受到衰老的影响。关于a-MCI中这些过程的完整性，我们知之甚少。因此，在健康的老年受试者和a-MCI和轻度AD患者中，记忆力和熟悉性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。由于阿尔茨海默病最早的病理改变涉及内侧的颞叶结构，因此假设行为学、事件相关电位和MRI测量将反映该区域在a-MCI中的受累情况，并在纵向评估中预测向AD的转变。具体地说，熟悉感是一种依赖于周围皮质的记忆形式，预计与老年对照组相比，a-MCI患者的熟悉感可能会受到损害。此外，在健康老龄化和a-MCI/AD之间，记忆的ERP相关性将不同，反映了前者的前额叶功能障碍和后者的海马体/内嗅觉病理。记忆行为估计和熟悉与容量MRI和ERP的关系将有助于进一步了解这些过程的解剖学和电生理学基础以及早期AD病理对它们的影响。此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中的记忆所产生的基础上。除了提高这些技能，应聘者还将学习一种新的调查方式--定量结构核磁共振。这种多模式方法的培训将使候选人在成为独立调查员后能够以新颖和灵活的方式处理科学问题。阿尔茨海默氏症已经是一个巨大的公共卫生负担，预计在未来30到40年内将急剧增长。损伤最小的患者可能会从潜在的疾病修改干预中受益最大。因此，寻求这里提出的早期诊断工具是至关重要的。

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.