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

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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.