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 衰老通常与一些有限的认知能力下降有关，尽管老龄化人口的一个亚群 将经历与阿尔茨海默病 (AD) 及其相关疾病相关的快速且进行性衰退 常见的前兆是轻度认知障碍 (MCI)，目前约有 510 万美国人患有 AD， 迫切需要了解这些智力衰退的神经生理学基础。 工作记忆 (WM) 过程是 MCI 中最早且受影响最严重的认知功能之一 注意力被定义为针对特定刺激的处理资源的优先分配。 或刺激，而 WM 表示用于持续认知的信息的在线临时存储 尽管神经心理学测试显示患有这些疾病的患者在这些领域存在明显的缺陷。 MCI 和 AD，对于其背后的神经振荡活动和计算动力学知之甚少 当前的研究旨在通过利用空间精度来部分弥补这一知识差距。 使用 MEG 进行脑磁图 (MEG) 成像的精细时间分辨率（即毫秒）， 我们将确定患有 MCI 和 AD 的成人注意力和 WM 功能障碍的神经生理学基础， 简而言之，参与者与人口统计学匹配的神经健康老年人样本进行比较。 将在 MEG 记录期间完成两项认知任务，一项是利用注意力处理，另一项是瞄准 在 WM 中，这两项认知任务已被证明可以在健康的人中产生强大的神经振荡活动。 生成的 MEG 数据将被转换到时频域并使用 将使用先进的波束形成方法。 检查低频（即 alpha 和 theta）振荡活动和动态功能连接 本质上，我们将识别统计异常的神经区域。 研究 MCI 和 AD 患者的振荡和功能连接，然后将这些神经数据与认知联系起来 我们的具体目标是：(1) 识别异常的 theta 和 alpha 振荡动力学。 MCI 和轻度 AD 患者中服务 WM 和注意力处理的神经区域，以及 (2) 量化 MCI 和轻度 AD 患者在这些相同的认知过程中动态功能连接。 为此，我们将利用最新的 MEG 和先进的源重建技术，神经振荡 分析方法和神经心理学评估来描绘认知的神经生理学基础 随着世界人口老龄化程度极不成比例，MCI 和 AD 患者的损伤。 未来几十年，AD 患病率将会上升，与此相关的沉重经济和社会负担 旨在更好地了解这种疾病并提供潜力的研究肯定会随之而来。 用于诊断和跟踪疾病进展的标记物可以通过指导来最终减少社会影响 为新疗法的开发提供信息并减轻总体财务负担。