Characterizing the Relationship between Brain Electrophysiology, Delirium, and Cognitive Decline

表征脑电生理学、谵妄和认知能力下降之间的关系

• 批准号: 10405121
• 负责人: Mouhsin Shafi
• 金额: $ 34.5万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10405121
• 关键词: Address; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer’s disease biomarker; Brain; Cerebrum; Characteristics; Cognitive; Delirium; Dementia; Disease; Effectiveness of Interventions; Elderly; Electroencephalography; Electromyography; Electrophysiology (science); Epilepsy; Evoked Potentials; Functional disorder; Future; Hospitalization; Impaired cognition; Impairment; Incidence; Individual; Inferior; Inflammation; Injury; Intervention; Knowledge; Light; Lobule; Magnetic Resonance Imaging; Measures; Morbidity - disease rate; Motor; Motor Cortex; Neurologic; Neuropsychology; Operative Surgical Procedures; Outcome; Parietal; Participant; Patients; Pattern; Performance; Physiology; Prefrontal Cortex; Prospective cohort; Recording of previous events; Recovery; Risk; Role; Severities; Therapeutic Intervention; Transcranial magnetic stimulation; Vitelliform macular dystrophy; base; cognitive function; cognitive performance; cognitive reserve; cohort; cost; effectiveness evaluation; functional independence; functional loss; high risk; image guided; indexing; individual patient; insight; mortality; neurophysiology; neuropsychiatric disorder; novel; postoperative delirium; prevent; recruit; resilience; response; stressor; therapeutic development; tool

ABSTRACT Delirium is a common and costly problem, affecting up to half of hospitalized older adults, and resulting in substantial morbidity, cognitive decline, loss of functional independence, and increased mortality. Delirium is particularly problematic in patients with Alzheimer's dementia who have an increased risk for delirium, and in whom delirium accelerates the rate of cognitive decline. However, our understanding of the neurological basis of the risk for and effects of delirium in a given individual remains very limited. This project seeks to address this important knowledge gap by utilizing magnetic resonance imaging (MRI)-guided (neuronavigated) transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) and electromyography (EMG) to evaluate cortical function in patients undergoing elective surgery. In a prospective cohort of 180 patients we will examine whether decreased brain network connectivity and altered mechanisms of cortical plasticity as characterized by TMS-EEG-EMG are associated with the risk of developing post-operative delirium. We will record TMS-evoked potentials (TEP) from dorsolateral prefrontal cortex, inferior parietal lobule, and primary motor cortex, before and after intermittent theta-burst stimulation (iTBS). We hypothesize that baseline EEG spectral power and connectivity, TMS-based measures of cortical reactivity and connectivity, and iTBS measures of cortical plasticity will be decreased in patients who subsequently develop delirium, and that patients with greater abnormalities in EEG features and TMS measures at baseline will have greater delirium severity and greater short-term cognitive decline after an episode of delirium. We will correlate neurophysiologic measures with changes in cognitive performance and subsequent cognitive decline in patients with versus without delirium. We hypothesize that EEG alpha power and connectivity, TMS reactivity, TEP cortical connectivity, and efficacy of the mechanisms of cortical plasticity will show greater decreases in patients with delirium than in those without, and will correlate with the magnitude of cognitive decline. Finally, in patients with a previously observed episode of delirium (in SAGES I) we will compare those with and without a history of delirium, and hypothesize that cortical physiology abnormalities will correlate with long-term cognitive decline after delirium (complicated delirium). Ultimately, our results will define neurophysiologic characteristics that can identify individuals with a vulnerable brain susceptible to delirium and subsequent cognitive decline, will provide novel tools to efficiently assess the effectiveness of interventions to help increase individual cerebral resilience and reduce the risk of delirium, and will guide development of therapeutic interventions to help normalize cerebral dysfunction and minimize long-term cognitive decline after delirium.

抽象的 谵妄是一种常见且代价高昂的问题，影响了多达一半的住院老年人，并导致 严重的发病率、认知能力下降、功能独立性丧失和死亡率增加。谵妄是 对于患有谵妄风险增加的阿尔茨海默病痴呆患者来说尤其成问题，并且 谵妄会加速认知能力下降的速度。然而，我们对神经学基础的理解 特定个体发生谵妄的风险和影响仍然非常有限。该项目旨在解决 利用磁共振成像 (MRI) 引导（神经导航）解决这一重要的知识差距 经颅磁刺激 (TMS) 与同时脑电图 (EEG) 和 肌电图（EMG）用于评估接受择期手术的患者的皮质功能。在前瞻性的 我们将在 180 名患者的队列中检查大脑网络连接是否下降以及神经机制是否改变 以 TMS-EEG-EMG 为特征的皮质可塑性与术后发生并发症的风险相关 谵妄。我们将记录背外侧前额皮质、下顶叶的 TMS 诱发电位 (TEP) 间歇性θ爆发刺激（iTBS）前后的小叶和初级运动皮层。我们假设 基线脑电图频谱功率和连接性、基于 TMS 的皮质反应性测量和 随后出现的患者的连通性和皮质可塑性的 iTBS 测量值将会降低 谵妄，并且基线时脑电图特征和 TMS 测量有较大异常的患者将出现 谵妄发作后谵妄的严重程度更高，短期认知能力下降也更大。我们将关联 神经生理学测量与患者认知表现的变化和随后的认知能力下降 有谵妄与无谵妄。我们假设 EEG α 功率和连通性、TMS 反应性、TEP 皮质连接性和皮质可塑性机制的功效将显示出更大的下降 患有谵妄的患者比没有谵妄的患者更容易出现谵妄，并且与认知能力下降的程度相关。最后，在 先前观察到谵妄发作的患者（在 SAGES I 中），我们将比较那些有和没有谵妄发作的患者 谵妄病史，并假设皮质生理学异常与长期认知能力相关 谵妄（复杂性谵妄）后下降。最终，我们的结果将定义神经生理学特征 可以识别出大脑脆弱、容易出现谵妄和随后认知能力下降的个体， 将提供新颖的工具来有效评估干预措施的有效性，以帮助提高个人 大脑恢复能力并降低谵妄的风险，并将指导治疗干预措施的开发 有助于使脑功能障碍正常化，并最大限度地减少谵妄后的长期认知能力下降。