Is damage to white matter always caused by problems with blood flow?

Lead Investigator: Professor Johannes Attems

Institution: Newcastle University

Grant type: Project grant

Duration: 3 years

Amount: £262,133

Scientific Title: The influence of cortical neurodegenerative pathology on white matter integrity

Why did we fund this project?

Comments from members of our Research Network:

'This novel approach offers the possibility of defining underlying processes that could enable clinicians to make much more accurate diagnoses of vascular and Alzheimer's dementia.'

'I think this research project embraces both cause and effect and offers a leap forward in understanding different pathologies related to dementias.'

'The results of this research should give some indication of the actual cause of the various types of dementia and assist in the preliminary diagnosis for early treatment.'

What do we already know?

The brain contains 'grey matter' and 'white matter'. Grey matter consists of the 'bodies' of nerve cells. White matter contains the connections between cells and different areas of the brain. Healthy white matter is essential for good communication between different brain regions.

In brains of elderly people this white matter may show damage, called white matter lesions. White matter lesions can be seen on Magnetic Resonance Imaging (MRI). It is generally believed that diseases affecting the blood vessels in the brain are the underlying cause for white matter lesions. Therefore, the identification of them on brain scans often leads to the assumption that the person has a disease of their brain blood vessels and this leads to a specific treatment.

However, white matter lesions are often seen in people with other forms of dementia, especially Alzheimer's disease, but automatic diagnosis of vascular dementia alone may preclude the prescription of treatments for Alzheimer's disease.

The extent to which these lesions in people with Alzheimer's disease is caused by vascular problems in addition to Alzheimer's, or simply as a result of underlying changes associated with Alzheimer's disease is unclear.

One way that other changes can cause white matter lesions is through the death of parts of nerve cells that form connections within the white matter, called 'Wallerian-like degeneration'. This may arise as part of Alzheimer's disease when these parts of the cell do not function properly, and so die.

Despite this, most people who have white matter lesions shown on brain scans will be diagnosed with blood vessel disease, even in its absence. This may lead to the wrong diagnosis, and so the wrong treatment, information and support.

What does this project involve?

This project will use donated brain tissue. The researchers will analyse the presence of white matter lesions within them. Using special techniques, they will identify whether the cause of the white matter lesions is related to blood vessels, or is due to other underlying neurodegeneration, such as that seen in Alzheimer's disease.

These brains have also been scanned using MRI scanners, and the researchers will look to see if the white matter lesions that show up on the scans appear differently depending on their underlying cause.

How will this benefit people with dementia?

These findings may have an impact on the way brain MRI images of older people are evaluated by clinicians. This will allow doctors to make a more specific and accurate diagnosis as to whether a person has Alzheimer's disease or a dementia caused by blood vessel disease (e.g. vascular dementia) or a combination of both. This is important, as the correct diagnosis will influence the type and nature of the treatment, information and support that is then given.