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

项目摘要 这项建议旨在通过在人类中使用正电子发射计算机断层扫描和核磁共振来收集数据，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的代谢率(CMRO2)和 葡萄糖(CMRGlc)，从而允许计算反映过量速率的有氧糖酵解(AG) 糖酵解超过氧化代谢所需的水平。先前的研究表明，大胆的信号是由 脑血流量(CBF)的变化超过CMRO2的变化，尤其是“任务负性”。 在任务执行过程中的大脑区域，组成了现在所谓的默认模式网络(DMN)。它是, 然而，目前尚不清楚在任务过程中，AG是否也在这些相同的区域减少或增加。 此外，由于阿尔茨海默病(AD)的病理特异地影响DMN，因此任务诱发的 AG的变化也会受到AD的影响。在这里，我们将收集任务诱发的代谢和大胆的fMRI数据 年轻人和老年人，包括有和没有阿尔茨海默病病理证据的成年人。我们的主要方法是 确定任务诱发的糖酵解如何与BOLD fMRI信号失活和激活有关，以及 确定衰老或AD是否会影响这些关系。在目标1中，我们将确定代谢相关因素 在年轻人的任务执行过程中，大胆的去激活。我们将进行FDG-PET来量化区域 CMRGlc，以及脑血流量和CMRO2的MRI测量，从而可以计算AG。我们会让 在休息和两个不同的任务中，这些测量与BOLD fMRI一起进行。然后我们将确定 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- 在患有AD的年轻人、老年人和老年人中，诱发的大脑代谢变化是不同的。我们会 进行与目标1相同的研究，但在老年健康成年人中(即，认知未受损的淀粉样生物标记物 阴性，没有其他神经系统疾病的证据)和无症状的有病理的老年人 阿尔茨海默病的证据(即淀粉样生物标志物阳性)。我们还将选择其中一项任务，以在 轻度阿尔茨海默病成人组。从这些数据中，我们将确定健康老龄化和阿尔茨海默病如何影响 任务诱发的大脑活动和代谢。我们希望这些数据具有很高的信息量，包括在 对许多正在进行的利用功能神经成像研究衰老和阿尔茨海默病的研究的解释 影响大脑生理。

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.