0928 Sleep, Mediating the Risk of Cognitive Impairment in Post-traumatic Stress Disorder via Noradrenalin Dysregulation

Abstract Introduction There is growing evidence that Post Traumatic Stress Disorder (PTSD) increases the risk of dementia, and sleep impairment in PTSD may contribute to this link. Increased cerebrospinal fluid (CSF) norepinephrine (NE) is associated with glymphatic dysfunction and poor neurocognitive outcomes. To understand the role of sleep in mediating the increased risk of dementia in PTSD, we investigated whether sleep-specific symptoms of PTSD are related to CSF NE level and cognitive function. Methods We analyzed a prospective study of combat Veterans with repetitive blast mild traumatic brain injury (mTBI). All underwent CSF sampling and the PTSD and DSM checklist 5 for military (PCL-M), a 17-item self-report measure reflecting DSM-IV symptoms of PTSD. We derived a sum score of each symptom cluster; Questions 1-5: “Re-Experiencing”, 6-12: “Avoidance and Negative Cognition and Mood” and 13-17: “Hypervigilance”. Among the 17 items, questions 2 and 13 are sleep-related symptoms. We calculated correlations of the sum score of each category with CSF NE level with and without sleep-specific questions (2: nightmare and 13: sleep disruption) with CSF NE levels. Trails A (attention and visual motor function) and Trail B (executive function) tests were performed. Results A total of 49 mTBI participants were included. A sum score of symptoms related to re-experiencing (r=0.34, p=0.001) and hyperarousal (r=0.3, p=0.03) were weakly correlated with elevated CSF NE. Excluding the sleep-specific symptom questions from these two categories attenuated the correlation (re-experiencing r=0.31, p=0.03; hyperarousal r=0.2, p=0.1). The scores of sleep-specific symptoms were separately examined, the correlation with CSF NE was (nightmare r=0.37, p=0.0009; sleep impairment r= 0.35, p=0.001). The symptom cluster related to avoidance and negative cognition and mood was not associated with NE level (r=0.15, p=0.9). Elevated CSF NE was strongly associated with lower Trials B performance (r=0.34, p=0.001). Trails A performance was not associated. Conclusion PTSD-associated sleep symptoms of nightmares and sleep disruption are most strongly associated with CSF NE. CSF NE is associated with worsening executive function measured by Trails B. Sleep symptoms may be the driver of the poor neurocognitive outcomes in patients with PTSD. Traditional symptom clusters of PTSD may not accurately reflect the risk of cognitive function. Support (if any)