Brain metabolism during task-evoked and spontaneous activity in aging and Alzheimer's disease

衰老和阿尔茨海默病中任务诱发和自发活动期间的大脑代谢

• 批准号: 10585419
• 负责人: Manu S Goyal
• 金额: $ 228.96万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-15 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585419
• 关键词: Address; Adult; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Amyloid; Area; Biological Markers; Blood flow; Brain; Brain region; Cell Respiration; Cerebrovascular Circulation; Cognitive; Data; Dementia; Disease Progression; Elderly; Exhibits; Functional Magnetic Resonance Imaging; Glucose; Glycolysis; Goals; Human; Impaired cognition; Language; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Metabolism; Oxygen; Pathologic; Persons; Physiological; Physiology; Positron-Emission Tomography; Psyche structure; Resources; Rest; Signal Transduction; Site; Task Performances; Testing; United States National Institutes of Health; Work; aerobic glycolysis; age effect; blood oxygen level dependent; brain metabolism; cohort; fluorodeoxyglucose positron emission tomography; healthy aging; metabolic rate; nervous system disorder; neural; neuroimaging; neurovascular coupling; pre-clinical; preservation; visual motor; young adult

PROJECT ABSTRACT This proposal aims to collect data using PET and MRI in humans to measure metabolic correlates of task-evoked neural activity. Our approach is unique in simultaneously measuring the metabolic rates of oxygen (CMRO2) and glucose (CMRGlc), thereby permitting the calculation of aerobic glycolysis (AG), which reflects the rate of excess glycolysis beyond that required for oxidative metabolism. Prior work has shown that the BOLD signal, driven by a change in cerebral blood flow (CBF) that exceeds changes in CMRO2, decreases in particular “task-negative” regions of the brain during task-performance, making up the now so-called default mode network (DMN). It is, however, presently unknown whether AG also decreases or increases in these same regions during a task. Moreover, since Alzheimer’s disease (AD) pathology specifically affects the DMN, it is possible that task-evoked changes in AG are also affected by AD. Here we will collect task-evoked metabolic and BOLD fMRI data in both young and older adults, including adults with and without pathologic evidence of AD. Our primary approach is to determine how task-evoked glycolysis relates to the BOLD fMRI signal deactivations and activations, and to determine whether aging or AD affect these relationships. In Aim 1, we will determine the metabolic correlates of BOLD deactivations during task performance in young adults. We will perform FDG-PET to quantitate regional CMRGlc, as well as MRI measurements of CBF and CMRO2, thus permitting calculation of AG. We will make these measurements alongside BOLD fMRI during rest and during two different tasks. We will then determine whether AG increases or decreases in the default mode network. In Aim 2, we will determine whether task- evoked changes in brain metabolism differ among young adults, older adults, and older adults with AD. We will perform the same studies as in Aim 1, but in older healthy adults (i.e., cognitively unimpaired, amyloid-biomarker negative, without other evidence of neurological disease) and in asymptomatic older adults with pathologic evidence of AD (i.e., amyloid-biomarker positive). We will also choose one of the tasks to further perform in a group of adults with mild AD dementia. From these data, we will determine how healthy aging and AD influence task-evoked brain activity and metabolism. We expect these data to be highly informative, including in the interpretation of numerous other ongoing studies utilizing functional neuroimaging to study how aging and AD influence brain physiology.

项目摘要 该建议旨在使用人类使用PET和MRI收集数据，以测量任务诱发的代谢相关性 神经活动。我们的方法在简单地测量氧的代谢率（CMRO2）和 葡萄糖（CMRGLC），从而允许计算有氧糖酵解（AG），这反映了多余的速率 糖酵解超出了氧化代谢所需的糖酵解。先前的工作表明，大胆信号由 超过CMRO2变化的脑血流（CBF）的变化，特别是“任务阴性” 在任务绩效期间大脑的区域，构成了现在所谓的默认模式网络（DMN）。这是， 但是，目前尚不清楚AG在任务期间这些区域是否也会下降或增加。 此外，由于阿尔茨海默氏病（AD）病理特异性影响DMN，因此可能会引起任务诱发的 AG的变化也受AD的影响。在这里，我们将在两者中收集任务诱发的代谢和大胆的fMRI数据 年轻人和老年人，包括有和没有病理证据的成年人。我们的主要方法是 确定任务诱发的糖酵解如何与大胆的fMRI信号失活和激活有关，并与 确定衰老还是AD是否影响这些关系。在AIM 1中，我们将确定代谢相关性 年轻人任务表现期间大胆停用。我们将执行FDG-PET来定量区域 CMRGLC以及CBF和CMRO2的MRI测量值，因此允许计算Ag。我们会做的 在休息期间和两个不同的任务中，这些测量与大胆的fMRI一起进行。然后我们将确定 AG是否在默认模式网络中增加还是减少。在AIM 2中，我们将确定是否任务 - 年轻人，老年人和AD的老年人的脑代谢的诱发变化不同。我们将 在AIM 1中进行相同的研究，但在老年人健康的成年人中（即，认知单纤维，淀粉样蛋白 - 生物标志物 阴性，没有其他神经系统疾病的证据）和病理不对称的老年人 AD的证据（即淀粉样蛋白生物标志物阳性）。我们还将选择其中一项任务以进一步执行 患有轻度AD痴呆的成年人。从这些数据中，我们将确定健康衰老和广告的影响 任务引起的大脑活动和代谢。我们希望这些数据有很高的信息丰富，包括 解释许多其他正在进行的研究使用功能神经影像来研究衰老和AD的研究 影响大脑生理。