Lung Injury Recovery and Cognitive Dysfunction Following Pneumonia: A Role for Sleep Fragmentation

Background: With an approximate of 19% of pneumonia hospitalisations leading to Intensive Care Unit (ICU) admission, an estimated 76 per 100,000 cases of severe pneumonia in the United States require admission to the ICU. Patients with severe pneumonia in the ICU have reported memory dysfunction that persists even after treatment underlying condition and discharge. Additionally, ICU patients have very poor sleep quality, as a consequence of their underlying condition and/or environmental factors. The interaction between pneumonia and ICU-associated poor sleep on cognitive dysfunction remains unexplored. Methods: Our lab has previously developed a murine model of ICU-associated sleep fragmentation (SF). Wild type C57BL/6J mice were exposed to pneumonia (PNA) with S. pneumoniae +/- ICU SF. After exposure, markers of lung injury were assessed. In separate experiments, mice were made to participate in the novel object test to assess short term memory testing over fixed time period intervals. Results: Control mice retained short-term memory with prolonged interaction with the novel object over a 5 week period. Mice exposed to sleep fragmentation alone for 7 days demonstrated worsening short term memory after 7 days return to normal sleep and persisted even up to 5 weeks, as demonstrated by approximately 50% time spent interacting with the novel object. Exposure to PNA resulted in significant lung injury with a recovery to baseline at 7 days. Exposure to SF after instillation of PNA resulted in delayed recovery from lung injury. However, exposure to PNA or PNA + sleep fragmentation resulted in worsened short-term memory at time of recovery from lung injury (7 days after installation) and persisted even after 5 weeks. Conclusion: Our data suggests that ICU-associated SF worsens recovery from lung injury in response to pneumonia and in and of itself can worsen short term memory. However, pneumonia has a profound effect on short term memory that is not exacerbated by ICU-associated SF. These data suggest that improving sleep quality may lead to improvements in pneumonia recovery but not improve cognitive dysfunction associated with severe pneumonia. Department of Defense - W81XWH-20-PRMRP-DA; NHLBI-HL 133413 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.