Strategies to prevent surgery-induced cognitive decline

Read about a research project we funded into: Pleiotrophic Strategies to Prevent Surgery-Induced Cognitive Decline in Normal and Vulnerable Aged Brain.

Lead investigator: Dr Helena Watts

  • Institution: Imperial College London
  • Grant Type: Research Fellowship
  • Grant amount: £218,644    
  • Start date: May 2013
  • Completion date: January 2017

What was the project, and what did the researchers do?

When people undergo surgery using general anesthesia, there is often a temporary period when normal thinking is affected resulting in symptoms such as delirium, and problems with memory recall and concentration.  

It is possible however, that this temporary period can last longer. When this is the case, it is termed postoperative cognitive dysfunction (POCD). In elderly people, the development of POCD can predict the development of dementia 3-5 years after surgery. 

This project aimed to use animal models to explore why older surgical patients can experience POCD that is associated with an earlier onset of dementia. The research team compared different mouse models to test the effects of three different drugs on Alzheimer's disease symptoms.

  • Initially, it was investigated whether surgery was more likely to lead to changes in the blood vessels, a common precursor to Alzheimer’s disease development. 
  • Following this, researchers aimed to replicate the effects of stressed cells seen in diabetes by feeding mice a high-sugar diet prior to surgery. They then looked at whether this had an effect on the symptoms of POCD observed after surgery by using a variety of tasks testing different forms of memory.
  • Finally, researchers tested three different drugs to assess their effectiveness at reducing changes seen in PODC. The drugs were tested on cells grown in the lab, which were studied for changes in their function and the proteins that they produce.

What were the key results?

The research team found that mice that had been fed on a high-sugar diet before surgery were more likely to have POCD and this appeared to damage their thinking and memory skills. These mice also showed a faster rate of aging compared to mice on a normal diet. 

Interestingly the team also found that the memory and thinking problems in mice were affected by changes to fluid channels called aquaporins which help to regulate the amount of fluid and the removal of waste from the brain. Surgery appeared to cause major changes in aquaporins in older mice and in particular the mice given high-sugar diets.

Using a drug called, Tropisetron, the research team were able to prevent POCD after surgery and in fact increased the number of aquaporin channels in on blood vessels. 

How will this help in the fight against dementia?

It’s vital we explore every avenue that may provide clues to how we can prevent Alzheimer’s disease. This project highlights changes in the brain that take place in the brain after surgery leading to Alzheimer’s and a possible drug that could be explored further to find out if it could reduce the risk of dementia in people. 

What happened next? Future work and additional grants

The research team are continuing this complex area of research to understand more about the role of aquaporins in the movement of fluids and removal of waste from the brain and how these systems are affected by ageing and dementia. They will also seek funding to continue to explore the possibility of using drugs such as Tropisetron to prevent dementia. 
 

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