Lead Investigator: Dr Helena Watts
Institution: Imperial College London
Grant type: Research Fellowship
Duration: Three years
Scientific Title: Pleiotrophic Strategies to Prevent Surgery-Induced Cognitive Decline in Normal and Vulnerable Aged Brain
Why did we fund this project?
Comments from members of our Research Network:
'I like this research. It seems to be practical and acheivable. It would potentially benefit many patients with or without dementia.'
'This is a vital topic and I fully support the proposal.'
'Important to gain further understanding of POCD to develop these protective strategies. Using existing drugs is a plus.'
What do we already know?
Often, when people undergo surgery that uses general anaesthesia, there is a temporary period (lasting up to a few days) when their normal thinking is affected.
This can include symptoms such as delirium, and problems with memory recall and concentration. This can last for more than a few days however, and it is then called postoperative cognitive dysfunction (POCD).
In older people, the development of POCD predicts the development of dementia 3-5 years after surgery.
However, up until now it has not been clear about the type of anaesthetic (local or general) or the duration that someone is under the anaesthetic that is the greatest predictor of POCD.
What does this project involve?
This project will compare different mouse models of diseases to test the effects of three different drugs on the symptoms of Alzheimer's disease.
The first part of the study will investigate whether surgery is more likely to result in changes to the blood vessels – often a precursor to the development of Alzheimer's disease – in older mice than younger.
The second part of the study will replicate the effects of stressed cells seen in diabetes, by feeding mice a high-sugar diet prior to surgery, and seeing if this has an effect on the symptoms of POCD seen after surgery.
Symptoms of POCD will be measured using a variety of tasks that test different forms of memory.
The final study will test three different drugs to assess whether they are effective at reducing the changes seen in POCD. These drugs will be tested on cells grown in the lab, which will be studied for changes in their function and changes to the proteins that they produce.
How will this benefit people with dementia?
This research will contribute to our understanding of the causes of POCD, the conditions that may put people at higher risk, and potential treatments that could be used to prevent its occurrence.
Many surgeries in older people are necessary and improve quality of life, so reducing the potential side-effects of this will be incredibly beneficial, as well as reducing the number of people who develop dementia.