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USA researchers gain insight into link between memory loss and critical illness

Patients who survive critical illness oftentimes exhibit long-lasting problems with memory, thinking and reasoning. In some instances, these difficulties in thinking resemble problems consistent with Alzheimer’s disease.

Published Mar 20th, 2019

Patients who survive critical illness oftentimes exhibit long-lasting problems with memory, thinking and reasoning. In some instances, these difficulties in thinking resemble problems consistent with Alzheimer’s disease.

Together, researchers at the University of South Alabama College of Medicine are addressing this public health crisis by studying the mechanisms leading to abrupt cognitive impairment among patients in intensive care units.

Their novel research – which explores the potential link between hospital-acquired bacterial pneumonia and cognitive decline – was recently published in the American Journal of Respiratory and Critical Care Medicine.

According to Troy Stevens, Ph.D., director of the USA Center for Lung Biology and Lenoir Louise Locke Chair of Physiology and Cell Biology at the USA College of Medicine, this research holds far-reaching potential to impact patient care, as previous research has not linked lung infection-induced amyloids to the decline in cognitive function.

“This work demonstrates that hospital-acquired lung infections cause production of amyloid proteins, which have been incriminated in dementia and Alzheimer's disease,” he said. “These proteins can be collected from the airways, the blood and the cerebrospinal fluid of infected patients and have the ability to kill cells and injure organs. The proteins are also difficult to get rid of, and are self-replicating and transmissible among cells. They not only injure the lung and other organs during infection, but they may continue to hinder organ repair after the lung infection is treated with antibiotics.”

Mike Lin, Ph.D., assistant professor of physiology and cell biology at the USA College of Medicine, serves as principal investigator on the project. “We found that patients in the ICU who contract nosocomial pneumonia have high levels of ‘toxins’ in their bodily fluids, compared to critically ill patients who do not have bacterial pneumonia,” he said.

According to Dr. Lin, the Centers for Disease Control and Prevention estimates that on any given day, about one in 25 hospital patients has at least one health-care associated infection. “Among the infections, bacterial pneumonia not only remains the most prevalent, but is also on the rise and is most closely linked to morbidity and mortality including cognitive decline,” he said.

Despite advances in medicine that have significantly prolonged life expectancy for patients in intensive care units who develop bacterial pneumonia, the disease-associated neurodegeneration and dementia is increasingly worrisome. “In the last 10 years, it has become recognized that one of the major problems exhibited among patients who become critically ill is impairment in cognitive function,” Dr. Lin added.

Ronald Balczon, Ph.D., associate professor of biochemistry and molecular biology at the USA College of Medicine, also serves as principal investigator of the study. “My role is to isolate the toxic reagents from experimental protocols and human specimens that Dr. Lin uses in his studies,” he said. “I do this by infecting cultured cells with the Pseudomonas bacteria and then collecting the materials that the cells secrete following infection, or purifying the toxins from human airway fluid, blood and cerebrospinal fluid. I then characterize those materials before transferring them over to Dr. Lin for his experiments.”

Dr. Lin credits his colleagues support, input from collaborators at the University of Alabama at Birmingham and extramural support for helping to secure publication in the American Journal of Respiratory and Critical Care Medicine. Last year, Dr. Lin was awarded a $1 million four-year grant from the National Institutes of Health to better understand the potential connection between bacterial infections and cognitive decline.

“It is extremely important to have extramural support to fund research, as scientific and clinic developments are costly,” he said. “This project provides a testable and previously unrecognized mechanism for the rampant cognitive impairment in survivors of critical illness with nosocomial pneumonia comorbidity.”

Drs. Stevens said this bench-to-bedside research holds extreme importance and speaks to the caliber of research conducted at USA. “We have talented investigators at our institution,” he said. “This work represents ongoing collaboration between researchers, graduate students and technical staff who contributed to this work.”

“Complex biomedical science requires a diverse and sophisticated group of talented investigators coming together to address important problems,” Dr. Stevens said. “In addition to the input added by Drs. Lin, Balczon and myself, Dr. Silas Leavesley and Diego Alvarez from USA played an instrumental part in this research. This work also required ongoing collaborations with critical care clinical-scientists, Jean-Francois Pittet and Brant Wagener, and a clinical microbiologist, Stephen Moser, at the University of Alabama at Birmingham. Sarah Voth, a Ph.D. candidate in the department of physiology and cell biology at USA, and Jessica Bell, technical staff, also contributed to this work.”

According to Dr. Balczon, he is excited to see what the future holds for this research. “The long term goal is to develop treatments that can be translated into patient care,” he said. “We will go wherever the data takes us and I am excited to be part of this innovative study.”

The American Journal of Respiratory and Critical Care Medicine (AJRCCM) publishes high-quality original papers, reviews, and clinical trials in respiratory, critical care, and sleep medicine to foster advances in translational research and clinical practice. The AJRCCM focuses on human biology and disease, as well as animal studies that contribute to the understanding of pathophysiology and treatment of diseases that affect the respiratory system and critically ill patients.

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