Neuroimaging Markers of Emerging Dysfunction In Preclinical Alzheimer Disease

临床前阿尔茨海默病中出现的功能障碍的神经影像标志物

• 批准号: 9312558
• 负责人: BRIAN Andrew GORDON
• 金额: $ 12.46万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9312558
• 关键词: Alzheimer' s Disease; Attention; Biological; Biological Assay; Biological Markers; Brain; Cerebrospinal Fluid; Clinical; Clinical Trials; Clinical assessments; Cognition; Cognitive; Cognitive deficits; Cohort Studies; Data; Dementia; Development; Diagnostic; Disease; Dorsal; Elderly; Episodic memory; Face; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Image; Impaired cognition; Impairment; Individual; Intervention; Knowledge; Maps; Measures; Medial; Mediating; Memory; Minor; Names; Neurobehavioral Manifestations; Neurons; Neuropsychological Tests; Normalcy; Outcome; Participant; Pathologic Processes; Pathology; Pattern; Phase; Positron-Emission Tomography; Prefrontal Cortex; Recruitment Activity; Research; Research Personnel; Rest; Risk; Sampling; Scanning; Senile dementia; Short-Term Memory; Stress; Support System; Symptoms; Techniques; Temporal Lobe; Time; Training; Work; analytical tool; attentional control; base; brain health; cognitive neuroscience; cognitive process; cognitive task; cognitive testing; demented; healthy aging; improved; in vivo; innovation; long term memory; longitudinal design; memory encoding; neuroimaging; neuroimaging marker; outcome forecast; pre-clinical; relating to nervous system; skills; support network; tool

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.

该提案的目的是支持候选人的发展和过渡 进入独立研究人员。概述的培训计划将使申请人配备 进行创新工作的必要技能，既涵盖基本研究，又 临床领域。阿尔茨海默氏病（AD）病理学的应计可能开始数十年 在认知症状发作之前。较高水平的病理增加了 痴呆症，但病理与认知之间的关系并不完美。功能 磁共振成像（fMRI）提供了一种非侵入性评估的方法 支持认知的大脑网络的完整性。因此，它可以提供更好的 与仅病理学的生物标志物相比，衡量大脑的健康。先前使用fMRI的工作 几乎只使用情节内存任务。这种方法是有限的 广告导致内存域以外的缺陷。目标1的目标是表征 使用三个 分别针对注意力控制，工作记忆和情节记忆的任务。 目标2的目的是将这些基于任务的fMRI范式的敏感性与 静止状态fMRI。 AIM 3的目标是将基于任务的fMRI数据与纵向联系起来 认知和从认知正态性到受损状态的过渡。这项工作将 提高我们对AD病理与神经元之间关系的理解 活性以及这种功能磁共振成像活性与纵向认知之间的关系。