Lead Investigator: Professor Stephen Wharton
Institution: University of Sheffield
Grant type: Project Grant
Duration: 36 months
Scientific Title: Diabetes, Defective Nutrient Signalling and Dementia: an Epidemiological Neuropathology Approach
Why did we fund this project?
Comments from members of our Research Network:
'This study could provide important information in identifying how diabetes contributes to cognitive decline and dementia. It could also lead to further important research'
'Diabetes and obesity are two ticking time bombs. Understanding their contribution to dementia is of immense importance'
'The project makes excellent use of a very important brain bank'
What do we already know?
Research has shown that diabetes can increase the risk of developing both Alzheimer's disease and vascular dementia. This is thought to be because the mechanisms behind diabetes development can damage small blood vessels in the brain, which is likely to contribute towards vascular dementia. It is also thought that diabetes-related blood vessel damage could lead to a reduced blood flow to the brain, which may be a factor in Alzheimer's disease development.
Professor Wharton believes that diabetes mechanisms may also directly cause damage to brain cells. He intends to use this project to further investigate the molecular reasons behind the apparent link between diabetes and dementia. The project will also determine whether a common condition called metabolic syndrome can influence dementia development. Metabolic syndrome encompasses a group of symptoms including obesity, high blood pressure, impaired blood glucose processing and impaired metabolic processes in cells.
What does this project involve?
The project will look at several aspects of diabetes and metabolic syndrome and how these could link to dementia development. This includes investigating the potentially harmful effect of raised glucose levels in the body, a hallmark of diabetes. The project will also investigate the levels of other nutrients known to be altered in diabetes and determine whether this has an effect on dementia risk.
The researchers will also focus on the effect of the hormone insulin, which does not function correctly in diabetes. There is a growing amount of research that indicates that brain cells cannot use insulin properly in Alzheimer's disease and this project will add to that understanding. The project will also focus on how diabetes mechanisms affect blood vessels in the brain, which is thought to be an important factor in dementia development, particularly in vascular dementia.
The research will make use of the Cognitive Function and Aging Study (CFAS) resource. This resource includes samples of brain tissue that have been donated to the study by members of the general population who were aged over 65. The researchers will use this tissue to measure several hallmarks of diabetes and determine if these are related to signs of Alzheimer's disease or vascular dementia. This includes investigating whether diabetes or metabolic syndrome can affect how genes work in certain cell types and whether these changes are linked to dementia development.
How will this benefit people with dementia?
Whilst diabetes is currently understood to be an important risk factor for dementia, not much is known about why this is the case. Understanding the relationship between diabetes and dementia will be important to tease apart the risks and causes that lie behind these two conditions. The study may help to define potential new mechanisms in disease development, including the role of diabetes in relation to brain cell damage.
The study has the potential to give insights into dementia prevention and to identify those at a higher risk of dementia due to diabetes-related mechanisms. This extra understanding will allow those affected to access the information that they need to manage their condition and reduce dementia risk.