Neuroimaging Markers of Emerging Dysfunction In Preclinical Alzheimer Disease

这项提议的目的是支持候选人的发展和过渡 成为一名独立的研究人员。概述的培训计划将使申请者具备 开展创新工作所需的技能，这些工作既包括初步研究，也包括 临床领域。阿尔茨海默病(AD)病理的积累可以从几十年开始 在认知症状出现之前。较高的病理水平会增加罹患 痴呆症，但病理和认知之间的关系并不完善。功能性 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，它可能会提供更好的 衡量大脑健康状况的生物标记物要比单纯的病理生物标记物更重要。使用功能磁共振成像的先前工作 几乎只使用情节记忆任务。这种方法的局限性在于 AD会导致内存域以外的缺陷。目标1的目标是描述 与AD临床前病理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的目标是比较这些基于任务的fMRI范例对 静息状态功能磁共振成像。目标3的目标是将基于任务的fMRI数据与纵向数据相关联 认知和从认知正常到受损状态的转变。这项工作将 提高对阿尔茨海默病病理与神经元关系的认识 活动，以及这种功能磁共振活动与纵向认知的关系。

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.