New research reveals that memory problems and other forms of cognitive impairment which develop after surgery or a serious illness are due to an inflammatory response in the brain.
Therefore, drugs that currently treat inflammatory diseases, such as rheumatoid arthritis, may be helpful in preventing mental decline after surgery, according to researchers at UCSF and colleagues at Imperial College London.
For some time, neurologists and anesthesiologists had no specific answer as to why some individuals, especially elderly patients, suffered from post-surgery memory loss, confusion and learning disorders.
Although it’s short-lived, cognitive problems are quite common in intensive care units, with symptoms occurring between 28 and 92 percent of hospitalized patients, depending on factors such as health status, age and type of surgery, said the authors.
These cognitive problems have also been associated with lower surgery success, increased risk of death, inability to cope and permanent dementia.
Until now, the disorder has not been clearly understood and no one knew how to treat it, according to senior author Mervyn Maze, MB ChB, professor and chair of the UCSF Department of Anesthesiology and Perioperative Care.
This study was the first to link the symptoms to an immune protein called tumor necrosis factor (TNF-α), a cytokine, and it also pinpointed a possible drug treatment, said Maze.
“Antibody therapies already are widely used against cytokines to prevent or treat inflammation, so we know that these are effective in humans,” said Maze, who began the research as a member of the Imperial College faculty before joining UCSF.
“This study suggests that one day we also might be able to use these therapies as a single, presurgical dose to prevent cognitive decline in susceptible patients.”
Prior studies have linked post-surgery mental decline to rising blood levels of interleukin-1 beta (IL-1β)—a molecule associated with inflammation. For this study, the researchers observed tumor necrosis factor (TNF-α), a protein known to regulate the inflammatory response before interleukin-1 is produced.
The study suggests that the TNF protein triggers an outflow of immune responses during surgery that activates the production of IL-1 in the brain, Maze said. This process is responsible for cognitive problems after surgery or critical illness.
“This is an important observation, as it demonstrates that cytokines are potential therapeutic targets in a wider range of diseases, not just autoimmune disease and cancer for which they are known targets,” said Sir Marc Feldmann, a pioneer in cytokine research in inflammatory disorders and professor at the Kennedy Institute of Rheumatology at Imperial College London.
“Moreover, effective therapeutics already are available, with a known safety profile and modest cost if used short term.”
The findings could lead to human clinical trials as soon as 12 months from now, the authors said. The study appears in an upcoming issue of the Proceedings of the National Academy of Sciences.
Source: University of California