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 该提案旨在使用PET和MRI在人类中收集数据，以测量任务诱发的代谢相关性。 神经活动我们的方法在同时测量氧代谢率（CMRO 2）和 葡萄糖（CMRGlc），从而允许计算有氧糖酵解（AG），其反映了过量葡萄糖的速率。 糖酵解超过氧化代谢所需。先前的工作表明，BOLD信号，由 脑血流量（CBF）的变化超过CMRO 2的变化，特别是“任务阴性”的降低 在任务执行过程中，大脑的区域，构成了现在所谓的默认模式网络（DMN）。是的， 然而，目前尚不清楚在任务期间AG在这些相同区域中是否也降低或增加。 此外，由于阿尔茨海默病（AD）病理学特别影响DMN，因此任务诱发的DMN可能是由神经元激活的。 AG的变化也受AD的影响。在这里，我们将收集任务诱发的代谢和BOLD功能磁共振成像数据， 年轻人和老年人，包括有和没有AD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与BOLD fMRI信号失活和激活的关系，以及 确定老化或AD是否影响这些关系。在目标1中，我们将确定代谢相关因素 年轻人在执行任务时BOLD失活的可能性。我们将进行FDG-PET，以定量区域 CMRG 1c以及CBF和CMR 02的MRI测量，从而允许计算AG。的中国梦作出 这些测量结果与BOLD功能磁共振成像在休息期间和两个不同的任务。然后我们将决定 在默认模式网络中AG是增加还是减少。在目标2中，我们将确定任务是否- 诱发的脑代谢变化在年轻人、老年人和患有AD的老年人中不同。我们将 进行与目标1相同的研究，但在老年健康成人中（即，认知未受损，淀粉样蛋白生物标志物 阴性，无其他神经系统疾病的证据）和无症状老年人病理性 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在 轻度AD痴呆的成年人。根据这些数据，我们将确定健康老龄化和AD的影响 任务诱发的大脑活动和新陈代谢。我们希望这些数据具有高度的信息性，包括在 解释了许多其他正在进行的研究，利用功能性神经成像来研究衰老和AD 影响大脑生理学