Using brain tissue to understand small vessel disease

Lead Investigator: Dr Catherine Humphreys

Institution: University of Edinburgh

Grant type: Clinical Training Fellowship

Duration: 4 years

Amount: £224,004

Scientific Title: Small vessel disease pathophysiology: human post-mortem brain tissue study with clinical-radiological-pathological correlation.

Why did we fund this?

Comments from our Research Network:

'I am surprised that so little appears to be known about SVD. If that is the case then this research will have major benefits in finding a cure for mixed dementias.'

'It is important to do this type of research and provides an opportunity to study the human brain directly.'

'The applicant shows enthusiasm for a career in dementia research, with clear goals.'

What do we already know?

Small vessel disease (SVD) is a common cause of dementia, being involved in up to 45 per cent of cases. This disease damages the brain by disrupting the blood flow to the cells. Due to a relative lack of research into the underlying mechanisms of disease, we still don't know how or why it develops. If we can understand this, future research will be successful in preventing and treating dementia.

The damage that SVD causes to the brain can be seen in magnetic resonance imaging (MRI) scans. It can also cause microscopic areas of damage that can only be studied by having access to the brain tissue and studying it under the microscope. There has been relatively little of this research compared to MRI studies. There are many reasons for this including problems obtaining human brain tissue, technical difficulties identifying small areas of damage in the brain at autopsy and lack of agreement between pathologists of how to describe the microscopic changes.

As a result we still don't understand the fundamental causes of SVD and dementia or how these microscopic areas of damage relate to those on MRI and to symptoms experienced by people with dementia.

What does this project involve?

Dr Humphreys will use donated brain tissue to study SVD at a cellular and genetic level to understand how and why it develops. She will relate this to how SVD appears on brain MRI scans and to lifestyle and health factors of participants to give us a deeper understanding of the disease process and what makes individuals vulnerable to SVD.

The results of existing genetic studies suggest that some people might be born with an increased risk of developing SVD. This project will build on this work, using it to direct the investigations that will be carried out on human tissue.

Definitions and terminology used in the scientific literature to describe SVD lesions on imaging and pathology have been used variably and inconsistently. This makes it difficult to find relevant information when trying to identify what research has already been done. Dr Humphreys plans to work with a collaboration to publish a consensus paper agreeing SVD terms and definitions to be used when identifying the condition in the brain.

How will this benefit people with dementia?

This project will increase our understanding of the fundamental underlying causes of SVD and how this causes dementia. This will enable research in the future to use this knowledge to learn how to prevent SVD and ultimately develop effective treatments for dementia.