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Researchers at the University of Rochester Medical Center (URMC) and Duke University Medical Center will collaborate on a study that investigates why some older patients, who become severely ill from COVID-19, develop delirium that can lead to brain damage and a dementia diagnosis.

Nearly 30-percent of patients hospitalized with COVID-19 develop delirium -- a state of confusion and impaired awareness. For severely ill patients the likelihood of delirium is closer to 70-percent. "The initial delirium, and then the cognitive, behavioral, and emotional problems -- commonly known as dysexecutive syndrome -- were arguably the most notable things in older people that had managed to survive COVID-19," said Harris Gelbard, M.D., Ph.D. Professor and Director, Center for Neurotherapeutics Discovery, who is also the principal investigator at URMC on this study which is being funded by the National Institute of Aging. "Nobody knows whether that's permanent or not because of the advanced age of the people this is impacting."

Using a model for inhaled lipopolysaccharide-based acute lung injury in mice to mimic what happens in the lungs of a severally ill COVID-19 patient, Gelbard and his colleague Niccolo Terrando, Ph.D. at Duke University Medical Center will look for specific events in the neurovascular unit —brain endothelial cells and their blood-brain barrier (BBB) forming tight junctions that support the central nervous system -- that can be traced back to cognitive impairment. Part of the hypothesis Gelbard is investigating is that scarring in the lung may cause platelets and inflammatory white cells to migrate to blood vessels in the central nervous system with the white cells traversing the BBB to cause neurologic disease. "The goal is to establish what the prerequisites are for lung injury that will lead to brain injury. And at that point, then we can start asking more complicated questions."

The researchers will also investigate how the body responds to URMC-099, an anti-inflammatory and neuroprotective agent developed by Gelbard, to prevent these sequelae. The use of behavior analysis at Duke and in vivo brain imaging at URMC will determine delirium-like changes in the mice.

Gelbard and Terrando are confident that this study will lead to a larger and longer study of the impact COVID-19 has on the brain of an older population. "If you could do something to prevent that in the first place, chances are you are going to do better, down the road."