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 收集人类数据，以测量任务诱发的代谢相关性 我们的方法在同时测量氧代谢率 (CMRO2) 和神经活动方面是独一无二的。 葡萄糖 (CMRGlc)，从而可以计算有氧糖酵解 (AG)，反映过量率 先前的研究表明，糖酵解超出了氧化代谢所需的范围。 脑血流量 (CBF) 的变化超过 CMRO2 的变化，特别是“任务阴性”下降 任务执行期间的大脑区域，构成了现在所谓的默认模式网络（DMN）。 然而，目前尚不清楚在任务期间这些相同区域的 AG 是否也会减少或增加。 此外，由于阿尔茨海默氏病 (AD) 病理学特别影响 DMN，因此任务诱发的神经网络可能 AG 的变化也受到 AD 的影响，在这里我们将收集两者的任务诱发代谢和 BOLD fMRI 数据。 年轻人和老年人，包括有或没有 AD 病理证据的成年人。 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 确定衰老或 AD 是否影响这些关系 在目标 1 中，我们将确定代谢相关性。 我们将进行 FDG-PET 来定量区域。 CMRGlc，以及 CBF 和 CMRO2 的 MRI 测量，从而允许计算 AG。 然后，我们将在休息期间和两项不同任务期间与 BOLD fMRI 一起进行这些测量。 在目标 2 中，我们将确定任务是否在默认模式网络中增加或减少。 年轻人、老年人和患有 AD 的老年人大脑代谢引起的变化是不同的。 进行与目标 1 相同的研究，但对象是老年健康成年人（即认知未受损、淀粉样蛋白生物标志物 阴性，没有神经系统疾病的其他证据）和患有病理性无症状的老年人 AD 的证据（即淀粉样蛋白生物标志物呈阳性）我们还将选择一项任务来进一步执行。 根据这些数据，我们将确定健康老龄化和 AD 的影响。 我们希望这些数据能够提供大量信息，包括在任务引起的大脑活动和新陈代谢方面。 对许多其他正在进行的研究的解释，利用功能性神经影像来研究衰老和 AD 之间的关系 影响大脑生理。