Neuroimaging Markers of Emerging Dysfunction In Preclinical Alzheimer Disease

本提案的目的是支持候选人的发展和过渡 成为一名独立研究员概述的培训计划将使申请人具备 必要的技能，进行创新工作，跨越主要研究和 临床领域。阿尔茨海默病（AD）病理学的积累可开始数十年 在认知症状出现之前更高水平的病理学会增加 痴呆，但病理和认知之间的关系是不完善的。功能 磁共振成像（fMRI）提供了一种非侵入性评估 大脑中支持认知的网络的完整性。因此，它可以提供更好的 衡量大脑健康的指标，而不仅仅是病理学的生物标志物。使用fMRI的先前工作 几乎只使用情景记忆任务。这种方法是有限的，因为 AD导致记忆领域以外的缺陷。目标1的目标是描述 与AD病理学的临床前水平相关的神经活动的改变， 分别针对注意力控制、工作记忆和情景记忆的任务。 目标2的目的是比较这些基于任务的功能磁共振成像范例的敏感性， 静息态功能磁共振成像目标3的目标是将基于任务的fMRI数据与纵向 认知和从认知正常状态到受损状态的转变。这项工作将 提高我们对AD病理学和神经元之间关系的理解， 活动，以及这种功能磁共振成像活动和纵向认知之间的关系。

The objective of this proposal is to support the candidate's development and transition into an independent researcher. The outlined training plan will equip the applicant with the necessary skills to conduct innovative work that spans both primary research and clinical domains. The accrual of Alzheimer's disease (AD) pathology can begin decades before the onset of cognitive symptoms. Higher levels of pathology increase the risk of dementia, but the relationship between pathology and cognition is imperfect. Functional magnetic resonance imaging (fMRI) provides a way to non-invasively assess the integrity of networks in the brain that support cognition. As such it may provide a better measure of the brain's health than biomarkers of pathology alone. Prior work using fMRI has almost exclusively utilized only episodic memory tasks. This approach is limited as AD leads to deficits beyond memory domains. The goal of Aim 1 is to characterize alterations in neural activity related to preclinical levels of AD pathology using three tasks that respectively target attentional control, working memory, and episodic memory. The goal of Aim 2 is to compare the sensitivity of these task-based fMRI paradigms to resting-state fMRI. The goal of Aim 3 is to relate task-based fMRI data to longitudinal cognition and the transition from cognitive normality to an impaired state. This work will improve our understanding of the relationship between AD pathology and neuronal activity, as well as the relationship between such fMRI activity and longitudinal cognition.