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

项目概要/摘要： 老年人入住重症监护室（ICU）治疗危重疾病/损伤， 机械辅助支持具有发展许多不良后天后遗症的高风险。 其中最严重的是发生谵妄，一种急性脑功能障碍综合征。谵妄增加 ICU住院时间延长、住院时间延长以及严重的发病率，甚至 增加死亡率。此外，谵妄的持续时间和严重程度会增加认知能力下降的风险， 阿尔茨海默病和相关痴呆症（ADRD）的发展。虽然没有药物可以 有效地治疗谵妄，可以预防或减少发生的非药物干预， 谵妄的持续时间和严重程度有很大的希望。然而，目前尚不清楚这些干预措施是否能 降低老年人认知能力下降和ADRD的下游风险。本行政补充 我将开始通过利用我们正在进行的减少谵妄， 老年ICU患者（DDM）中的音乐临床试验（R 01 AG 067631），通过延长ICU后 脑健康的神经心理学评估，并研究共同的病理生理途径 谵妄和认知能力下降/ADRD之间的联系假设DDM ICU治疗会导致水平较低 急性神经炎症，小胶质细胞和星形胶质细胞活化，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后认知结果改善， 通过降低认知障碍和ADRD的风险，ADRD病理学进展。我们将测试这个 假设有两个具体的目的：A1）测试DDM治疗在减缓后 与注意力相比，机械通气患者的ICU认知下降 控制将在出院后6个月和12个月完成神经心理学评估。 A2）确定DDM治疗是否与老年人中ADRD病理学进展较慢相关。 重症监护室的成年幸存者神经变性的血液生物标志物（神经丝光），磷酸化tau-181 胶质细胞酸性蛋白和S100 B; AD病理学（Aβ42/Aβ40），血管病理学（C-反应蛋白） 将在ICU、住院后6个月和12个月收集炎症（白细胞介素1、6和8） 放电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R 01提案，以测试DDM ICU音乐干预的有效性，以降低 老年ICU幸存者的认知下降和ADRD，并描述神经保护作用 音乐在ADRD高危患者中的作用机制。

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.