How LC Integrity in Older Adults Mediates Perceptual and Memory Processes

老年人的 LC 完整性如何调节知觉和记忆过程

基本信息

批准号：
10613285
负责人：
XIAOPING P HU
金额：
$ 38.87万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10613285
关键词：
Address Adult Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Amygdaloid structure Arousal Attention Award Awareness Behavior Behavior assessment Behavioral Biological Markers Brain Brain region Cerebellum Cognition Collaborations Computer Analysis Control Groups Data Data Set Diagnosis Disease Elderly Enrollment Exertion Foundations Functional Magnetic Resonance Imaging Funding Gays Goals HIV HIV Infections HIV-associated neurocognitive disorder Hand High Prevalence Hippocampus (Brain)Human Image Impaired cognition Individual Individual Differences Intervention Learning Link Magnetic Resonance Imaging Measures Mediating Memory Methods Mission Modality Mydriasis National Institute of Mental Health National Institute of Neurological Disorders and Stroke Neocortex Nerve Degeneration Neurocognitive Deficit Neurodegenerative Disorders Neurons Norepinephrine Parkinson Disease Pathology Patient Self-Report Pattern Perception Performance Persons Play Pontine structure Population Psychophysics Public Health Publications Research Research Personnel Research Project Grants Resolution Role Series Services Source Stress Structure Surveys Task Performances Tegmentum Mesencephali Testing Thalamic structure United States National Institutes of Health Woman age stratification base candidate marker cognitive ability cognitive function cognitive neuroscience cognitive performance cognitive process cognitive testing community based research design digital grasp in vivo insight interest locus ceruleus structure memory process men neurobehavioral neuroimaging neuromelanin neuron loss normal aging novel novel therapeutics preservation recruit response stressor tractography

项目摘要

The goal of this supplement is to understand relationships between HIV infection and neurocognitive decline in people aging with HIV. This is in the context of the larger project to understand how individual differences in the structure and function of Locus Coeruleus (LC) moderate perception and memory in an older adult population. There is substantial evidence that the LC circuit plays a central role in cognitive processes and neuronal loss in LC is known to occur in neurodegenerative disorders such as ADRD and PD. Integrity of LC neurons is hypothesized to mediate the preservation of cognitive abilities during normal aging as well. To date, however, there exists a dearth of research that either characterizes differential effects of LC integrity or details relationships between LC integrity and cognitive function in older adult humans. There is even less information on how the LC ages in people living with HIV (PLWHIV). More generally, the link between LC activity and cognitive processes has not been well characterized in humans. Historical reasons for this is that the LC has been difficult to image due to its small size and thus most human research makes inferences about LC function by using pupil dilation as a surrogate measure. To overcome existing limitations in the field, we propose a series of detailed psychophysical and MRI-based studies in older adults aimed to characterize how LC structure and function moderates behavior and in turn how this is mediated by activity in intermediate brain regions known to be involved in perceptual and memory processes. We further propose computational approaches to characterize individual differences in how LC circuit integrity relates to different patterns of cognitive performance across tasks, and advanced neuroimaging methods to localize and image the LC, which have been pioneered by our group. Using MRI-based methods, we will examine LC integrity using high-resolution neuromelanin-sensitive structural imaging, tractography and functional connectivity. This approach will allow us to identify candidate biomarkers of LC circuit integrity. Overall this study will provide an important and much needed understanding of how LC integrity underlies cognitive declines in older adults, including PLWHIV. By combining advanced neuroimaging, well-controlled behavioral assessment, and computational analysis, we expect to uncover previously inaccessible in vivo mechanisms of LC modulation and generate a unique dataset to address fundamental mechanistic questions of how the LC integrity moderates cognition, how this varies across older adults with and without HIV and the extent to which relationships between LC and cognition are generalized or individualized to particular domains. The resulting understanding of LC circuit can help explain how dysfunctional modulatory circuits may generate cognitive declines or be implicated in normal aging, those aging with HIV and Alzheimer’s and Alzheimer’s related disorders. This, in turn, has potential to support non-invasive methods for diagnosing pathologies associated with LC decline and developing new treatments.

这种补充的目的是了解HIV感染与神经认知能力下降之间的关系患有艾滋病毒的人。这是在更大的项目的背景下了解个体差异如何老年人群中层层基因座（LC）中等感知和记忆的结构和功能。有大量证据表明，LC电路在认知过程中起着核心作用，在已知LC发生在ADRD和PD等神经退行性疾病中。 LC神经元的完整性是假设在正常衰老期间也介导了认知能力的保留。但是，迄今为止存在研究的死亡，该死亡是表征LC完整性的差异影响或细节关系的差异在老年人的LC完整性和认知功能之间。关于LC的信息甚至更少患有艾滋病毒（PLWHIV）的人的年龄。更一般地，LC活动与认知过程之间的联系人类的特征还没有很好。这样做的历史原因是LC很难成像由于其尺寸很小，因此大多数人类研究通过使用学生词典来推断LC功能作为替代测量。为了克服该领域的现有限制，我们提出了一系列细节对老年人的心理物理和基于MRI的研究，旨在表征LC的结构和功能调节行为，进而由中间大脑区域的活动介导的行为，这是如何介导的参与感知过程和记忆过程。我们进一步提出计算方法来表征 LC电路完整性如何与不同的认知表现模式相关的个体差异任务以及先进的神经影像学方法来本地化和图像LC，这已被我们的策划团体。使用基于MRI的方法，我们将使用高分辨率神经元素敏感的LC完整性检查LC完整性结构成像，拖拉术和功能连通性。这种方法将使我们能够确定候选人 LC电路完整性的生物标志物。总体而言，这项研究将提供重要且急需的理解 LC完整性在包括PLWHIV在内的老年人中的认知能力下降。通过结合高级神经影像学，控制良好的行为评估和计算分析，我们希望发现以前无法访问LC调制的体内机制，并生成一个独特的数据集来解决 LC完整性如何调节认知，这种变化如何，较旧的基本机制问题患有和没有艾滋病毒的成年人以及液晶与认知之间的关系在多大程度上被普遍化或个性化到特定领域。对LC电路的最终理解可以帮助解释功能失调调节电路可能会在正常衰老，艾滋病毒和阿尔茨海默氏症和阿尔茨海默氏症相关的疾病。反过来，这有可能支持非侵入性方法诊断与LC下降和开发新疗法有关的病理。