Oscillatory markers of cognitive deficits in patients with Alzheimer's disease

阿尔茨海默病患者认知缺陷的振荡标志物

• 批准号: 9529218
• 负责人: Alex I Wiesman
• 金额: $ 4.19万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9529218
• 关键词: Adult; Affect; Aging; Alzheimer' s Disease; American; Anterior; Area; Attention; Brain; Brain Mapping; Brain imaging; Clinical; Cognitive; Cognitive deficits; Collection; Data; Diagnosis; Disease; Disease Progression; Education; Elderly; Electrophysiology (science); Evolution; Exhibits; Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Grouping; Human; Image; Impaired cognition; Impairment; Income; Information Storage; Knowledge; Left; Link; Literature; Magnetoencephalography; Maintenance; Maps; Memory; Memory impairment; Methods; Neurodegenerative Disorders; Neurologic; Neurons; Neuropsychological Tests; Neuropsychology; Output; Parietal; Participant; Pathologic; Pathology; Patients; Pattern; Phase; Population; Prefrontal Cortex; Prevalence; Process; Psyche structure; Reporting; Research; Research Project Grants; Resources; Rest; Retrieval; Role; Sampling; Scientist; Short-Term Memory; Signal Transduction; Source; Specificity; Stimulus; Structure of supramarginal gyrus; Subgroup; Techniques; Time; Training; United States; accurate diagnosis; aging population; base; career; cognitive ability; cognitive function; cognitive neuroscience; cognitive performance; cognitive process; cognitive task; experience; healthy aging; hemodynamics; imaging modality; indexing; information processing; insight; memory process; mild cognitive impairment; millisecond; neuroimaging; neurophysiology; novel; operation; pathological aging; prevent; reconstruction; relating to nervous system; response; statistics; temporal measurement; therapy development; tool

ABSTRACT/PROJECT SUMMARY Aging is typically associated with some limited cognitive decline, although a subgroup of the aging population will experience the rapid and progressive declines that are associated with Alzheimer’s disease (AD) and its common precursor, mild cognitive impairment (MCI). With around 5.1 million Americans living with AD today, there is an immediate need to understand the neurophysiological basis of these mental declines. Attention and working memory (WM) processes are among the earliest and most severely affected cognitive functions in MCI and AD. Attention is defined as the preferential allocation of processing resources towards a specific stimulus or stimuli, whereas WM denotes the on-line temporary storage of information to be used in ongoing cognitive processing. Although neuropsychological testing has shown a clear deficit in these domains in patients with MCI and AD, far less is known about the neural oscillatory activity and computational dynamics that underlie these deficits. The current study aims to partially remedy this knowledge gap by utilizing the spatial precision and exquisite temporal resolution (i.e., millisecond) of magnetoencephalographic (MEG) imaging. Using MEG, we will determine the neurophysiological bases of attentional and WM dysfunction in adults with MCI and AD, as compared to a demographically-matched sample of neurologically-healthy older adults. Briefly, participants will complete two cognitive tasks during MEG recording, one tapping attentional processing and another aimed at WM. Both of these cognitive tasks have been shown to produce robust neural oscillatory activity in healthy controls. The resulting MEG data will be transformed into the time-frequency domain and imaged using an advanced beamforming approach. The output dynamic functional maps of electrical neural activity will be used to examine low frequency (i.e., alpha and theta) oscillatory activity and dynamic functional connectivity among regions serving attention and WM processes. Essentially, we will identify the statistically anomalous neural oscillations and functional connectivity in patients with MCI and AD, and then link these neural data to cognitive performance metrics. Our specific aims are: (1) To identify aberrant theta and alpha oscillatory dynamics in neural regions serving WM and attention processing in patients with MCI and mild AD, and (2) to quantify dynamic functional connectivity during these same cognitive processes in patients with MCI and mild AD. To this end, we will utilize the latest MEG and advanced source reconstruction techniques, neural oscillatory analysis methods, and neuropsychological assessment to delineate the neurophysiological bases of cognitive impairments in patients with MCI and AD. With the world population aging in a highly disproportionate manner, AD prevalence is set to rise in future decades, and the hefty economical and societal burdens associated with the disease will certainly follow. Research aimed at better understanding the disease and providing potential markers for diagnosing and tracking disease progression may ultimately reduce the societal impact, by guiding and informing novel treatment development and reducing the overall financial burden.

摘要/项目摘要 衰老通常与某些认知能力下降有关，尽管人口衰老的亚组 将体验与阿尔茨海默氏病（AD）及其的快速而渐进的下降 共同的前体，轻度认知障碍（MCI）。今天约有510万美国人住过广告， 立即需要了解这些心理下降的神经生理基础。注意和 工作记忆（WM）过程是MCI中最早，最严重影响的认知功能 和广告。注意被定义为对特定刺激的加工资源的首选分配 或刺激，而WM表示要在正在进行的认知中使用的信息的在线临时存储 尽管神经心理学测试在这些领域中显示出明确的防御 MCI和AD，对基于的神经振荡活性和计算动力学知之甚少 这些缺陷。当前的研究旨在通过使用空间精度部分记住这一知识差距 以及磁脑（MEG）成像的独家临时分辨率（即毫秒）。使用MEG， 我们将确定MCI和AD成人注意力和WM功能障碍的神经生理基础， 与神经系统健康的老年人的人口统计学样本相比。简而言之，参与者 将在MEG录制过程中完成两项认知任务，一项敲击注意力处理，另一个针对 在Wm。这两种认知任务均已证明可以在健康中产生强大的神经振荡活性 控件。由此产生的MEG数据将被转换为时频域，并使用 先进的波束形成方法。将使用电神经活动的输出动态功能图 检查低频（即α和theta）振荡活动和动态功能连接 引起关注和WM过程的地区。本质上，我们将确定统计上异常的中性 MCI和AD患者的振荡和功能连通性，然后将这些神经数据与认知联系起来 性能指标。我们的具体目的是：（1）确定在 MCI和轻度AD患者的WM和注意力处理的神经区域以及（2）量化 MCI和轻度AD患者的这些相同认知过程中的动态功能连通性。到 这一目的，我们将利用最新的MEG和高级源重建技术，神经振荡 分析方法和神经心理学评估来描述认知的神经生理基础 MCI和AD患者的障碍。随着世界人口以高度不成比例的方式衰老， 广告患病率将在未来的几十年中升高，与之相关的经济和社会伯恩斯（Burnens） 这种疾病肯定会随之而来。旨在更好地理解疾病并提供潜力的研究 诊断和跟踪疾病进展的标记最终可能会通过指导来减少社会影响 并为新颖的治疗开发提供信息，并减少整体金融伯恩。