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

项目摘要/摘要： 住进重症监护病房(ICU)接受侵入性危重疾病/损伤治疗的老年人 机械通气支持具有发生一些后天不良后遗症的高风险。 其中最可怕的是精神错乱，这是一种急性脑功能障碍综合征。神志不清增多 长时间住ICU的风险、住院时间的延长以及严重的发病率甚至 死亡率上升。此外，精神错乱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(ADRD)的发展。虽然没有任何药物可以 有效治疗精神错乱，非药物干预可以预防或减少这种情况的发生， 精神错乱的持续时间和严重程度很有希望。然而，目前尚不清楚这些干预措施是否能 减少老年人的认知衰退和ADRD的下游风险。本行政副刊 将开始通过利用我们正在减少的Delirium来解决这一重大的科学差距 MUSIC在老年ICU患者(DDM)中的临床试验(R01AG067631)延长ICU后时间 脑健康的神经心理学评估和共同的病理生理通路研究 精神错乱和认知功能衰退/ADRD。假设DDM ICU治疗会导致较低水平 急性神经炎，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精神错乱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 ADRD的病理进展通过降低认知损害和ADRD的风险。我们将对此进行测试 有两个具体目的的假说：A1)测试DDM治疗在减缓后发作率方面的有效性 机械通气患者ICU认知功能减退与注意力的比较 控制力。神经心理评估将在出院后6个月和12个月完成。 A2)确定DDM治疗是否与老年人ADRD病理进展缓慢有关 成年ICU幸存者。神经退行性变的血液生物标记物(神经丝光)，磷酸化tau-181 胶质纤维酸性蛋白、S100B、AD病理学(Aβ42/Aβ40)、血管病理学(C反应蛋白) 炎症(白介素1、6和8)将在入院后6个月和12个月在ICU收集 出院。分析将包括描述性统计和混合效应模型。结果将用于 通知未来的R01提案，以测试DDM ICU音乐干预的有效性，以降低 老年ICU存活者的认知功能下降和ADRD，以及神经保护的特征 ADRD高危患者的MUSIC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.