Simple drug treatments may help older adults recover from memory decline and postoperative cognitive impairment, according to new research in mice by scientists at the University of Illinois Urbana-Champaign.
The research team led by Uwe Rudolph, professor and head of comparative biosciences at the university, conducted two studies exploring different aspects of cognitive impairment. The first study focused on cognitive issues that can occur after surgery, which are common among older adults. Rudolph noted that "10% of adults over the age of 60 still have deficits to learning, memory and executive function three months after surgery." He added, "If you then multiply that by the number of surgeries that are done on people 60 years and over, the number is very significant."
In this study, published in PNAS Nexus, researchers examined whether propofol—a commonly used anesthetic—could help with cognition following surgery. Previous studies have suggested propofol might improve cognition in Alzheimer's disease models but could be harmful at high doses. To address this question, the team performed surgery on older mice and administered intermittent doses of propofol starting before surgery.
Illinois postdoctoral researcher Rajasekar Nagarajan, first author of both studies, explained that previous research often used younger mice or did not include actual surgical procedures for older mice. This made it difficult to distinguish between effects caused by anesthesia versus those caused by surgical trauma.
The findings showed that mice receiving propofol performed better on various cognitive tasks after surgery. These improvements lasted for five days after a dose despite propofol being cleared from the body within hours. The researchers observed increased levels of certain GABA receptors—important for learning and memory—in the hippocampus region of treated mouse brains as well as reduced inflammation and cell death markers.
"It is well known that general anesthesia and surgery may result in cognitive impairments, especially in older individuals. It is surprising and interesting that a general anesthetic like propofol actually can improve cognitive function after surgery in aged individuals," Nagarajan said. He added that ongoing experiments are testing compounds targeting specific GABA receptor subtypes affected by propofol to see if they might prevent postoperative cognitive deficits.
The second study, published in Pharmacology Research and Perspectives, looked at age-related memory decline using a mouse model designed to mimic aging in the hippocampus (pseudo-aged mice). Researchers tested whether daily intranasal insulin administration could improve memory performance.
After nine days of treatment with insulin nasal spray, pseudo-aged mice showed improved working memory, recognition memory, and associative memory compared to controls. Molecular analysis revealed that these improvements were linked to reductions in neural inflammation markers.
"Together, the results suggest that intranasal insulin may provide a noninvasive therapeutic approach for mitigating age-related cognitive decline by modulating neuroinflammatory mechanisms," wrote the authors.
Rudolph also mentioned possible connections between intranasal insulin's effects and those seen with propofol: "There are some indications that intranasal insulin has similar effects as propofol for cognition after surgery as well." The team plans further studies to clarify whether specific GABA-A receptors are involved in both treatments' actions and to identify which neuron types are responsible for these effects.
This research was funded by grants from the National Institute of General Medical Sciences at the U.S. National Institutes of Health (award numbers R01GM128183 and R35GM153232).
