Decreasing Delirium through music (DDM) in critically ill older adults.

通过音乐（DDM）减少危重老年人的谵妄。

• 批准号: 10711036
• 负责人: Linda L Chlan
• 金额: $ 38.87万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10711036
• 关键词: Acute; Address; Administrative Supplement; Admission activity; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid beta-42; Astrocytes; Biological; Biological Markers; Blood; Blood Vessels; Brain; C-reactive protein; Clinical Trials; Cognitive; Collaborations; Control Groups; Critical Illness; Data; Delirium; Development; Diagnosis; Elderly; Enrollment; Ensure; Failure; Funding; Future; Glial Fibrillary Acidic Protein; Hospitalization; Hospitals; Hydrocortisone; Impaired cognition; Incidence; Indiana; Inflammation; Inflammatory; Injury; Intensive Care Units; Interleukin-1; Interleukin-6; Intervention; Investigation; Knowledge; Light; Link; Literature; Measures; Mechanical ventilation; Mechanics; Modeling; Morbidity - disease rate; Music; Nerve Degeneration; Neuronal Injury; Neuropsychology; Noise; Norepinephrine; Outcome; Pathology; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Physical Rehabilitation; Production; Protocols documentation; Research; Research Personnel; Risk; Risk Factors; Risk Reduction; Seasons; Severities; Survivors; Sympathetic Nervous System; Syndrome; Testing; Time; Training; attentional control; blood-based biomarker; brain dysfunction; brain health; cohort; cytokine; efficacy testing; group intervention; high risk; improved; indexing; interest; mild cognitive impairment; modifiable risk; mortality; neurofilament; neuroinflammation; neuroprotection; novel; prevent; randomized, clinical trials; response; scale up; sedative; staff intervention; statistics; tau-1; treatment group

Project Summary/Abstract: Older adults admitted to the intensive care unit (ICU) for treatment of critical illness/injury with invasive mechanical ventilatory support are at high-risk for development of a number of adverse acquired sequelae. One of the direst is occurrence of delirium, a type of acute brain dysfunction syndrome. Delirium increases risk for prolonged ICU stay, increased duration of hospitalization as well as significant morbidity and even increased mortality. Further, duration and severity of delirium elevates the risk of cognitive decline and development of Alzheimer's disease and related dementias (ADRD). While there are no medications that effectively treat delirium, nonpharmacological interventions that can prevent or reduce the occurrence, duration and severity of delirium hold great promise. However, it is not known if these interventions can reduce cognitive decline and the downstream risk of ADRD in older adults. This administrative supplement will begin to address this significant scientific gap by leveraging our on-going Decreasing Delirium through Music in Older Adult ICU Patients (DDM) clinical trial (R01AG067631) by extending the post-ICU neuropsychological assessments of brain health and investigate the shared pathophysiological pathways between delirium and cognitive decline/ADRD. DDM ICU treatment is hypothesized to result in lower levels of acute neuroinflammation, microglial and astrocyte activation, and neuronal injury which will reduce the duration and severity of ICU delirium and lead to improved post-ICU cognitive outcomes, slower progression of ADRD pathology through lower risk of cognitive impairment and ADRD. We will test this hypothesis with two specific aims: A1) Test the efficacy of the DDM treatment in slowing the rate of post- ICU cognitive decline in mechanically ventilated patients as compared to attention control. Neuropsychological assessments will be completed at 6- and 12-months after hospital discharge. A2) Determine whether DDM treatment is associated with slower progression of ADRD pathology in older adult ICU survivors. Blood biomarkers of neurodegeneration (neurofilament light), phosphorylated tau-181 glial fibrillary acidic protein, and S100B; AD pathology (Aβ42/Aβ40), vascular pathology (C-reactive protein) and inflammation (interleukins 1, 6, and 8) will be collected in ICU, 6- and 12 months after hospital discharge. Analysis will consist of descriptive statistics and mixed effects models. Results will be used to inform a future R01 proposal to test the efficacy of DDM ICU music interventions to reduce the risk of cognitive decline and ADRD in older adult ICU survivors, and to characterize the neuroprotective mechanisms of music in patients at high risk for ADRD.

项目摘要/摘要： 入住重症监护病房 (ICU) 接受侵入性危重疾病/损伤治疗的老年人 机械通气支持存在产生许多不良后天后遗症的高风险。 其中最可怕的是发生谵妄，这是一种急性脑功能障碍综合征。谵妄增加 延长 ICU 停留时间、增加住院时间以及显着发病率的风险，甚至 死亡率增加。此外，谵妄的持续时间和严重程度会增加认知能力下降和 阿尔茨海默病和相关痴呆症（ADRD）的发展。虽然没有药物可以 有效治疗谵妄，非药物干预可以预防或减少谵妄的发生， 谵妄的持续时间和严重程度很有希望。但目前尚不清楚这些干预措施是否能够 减少老年人的认知能力下降和 ADRD 的下游风险。本行政补充 将通过利用我们正在进行的减少谵妄来开始解决这一重大科学差距 音乐在老年 ICU 患者 (DDM) 中的临床试验 (R01AG067631) 通过延长 ICU 后时间 对大脑健康进行神经心理学评估并研究共同的病理生理学途径 谵妄和认知能力下降/ADRD 之间的关系。假设 DDM ICU 治疗可导致较低水平 急性神经炎症、小胶质细胞和星形胶质细胞激活以及神经元损伤，这将减少 ICU 谵妄的持续时间和严重程度，并导致 ICU 后认知结果的改善，速度较慢 通过降低认知障碍和 ADRD 风险来控制 ADRD 病理进展。我们将测试这个 有两个具体目标的假设： A1) 测试 DDM 治疗在减缓术后死亡率方面的功效 与注意力相比，ICU 机械通气患者的认知能力下降 控制。神经心理学评估将在出院后 6 个月和 12 个月完成。 A2) 确定 DDM 治疗是否与老年人 ADRD 病理进展缓慢相关 成年 ICU 幸存者。神经退行性变的血液生物标志物（神经丝光），磷酸化 tau-181 胶质纤维酸性蛋白和S100B； AD病理（Aβ42/Aβ40）、血管病理（C反应蛋白） 住院后 6 个月和 12 个月，将在 ICU 收集炎症（白细胞介素 1、6 和 8） 释放。分析将包括描述性统计和混合效应模型。结果将用于 告知未来的 R01 提案，以测试 DDM ICU 音乐干预的功效，以降低以下风险： 老年 ICU 幸存者的认知能力下降和 ADRD，并表征神经保护作用 ADRD 高危患者的音乐机制。