Congratulations to Dr Sasha Philbert who has been awarded a prestigious 4-year Alzheimer’s Society Fellowship. Dr Philbert’s project aims to improve the diagnostic accuracy of vascular dementia by distinguishing it from early-stage Alzheimer’s disease.

Dr Philbert’s research will focus on using sodium MRI scans to distinguish between vascular cognitive impairment and early-stage Alzheimer’s disease. The study will measure sodium levels in the brains of individuals with these conditions and healthy controls. Additionally, it will investigate the link between sodium levels and energy supply in the brain, as well as the impact of blood vessel damage on sodium regulation.

His research aims to improve diagnostic accuracy for vascular dementia, leading to better-targeted treatments and reducing unnecessary side effects from inappropriate therapies. If successful, the findings could pave the way for simpler, more affordable diagnostic tests and inform future research into treatments for vascular dementia.

Introduction to the research area and project: what role does sodium play in vascular dementia? 

Background

Vascular dementia makes it hard to think, make decisions, and solve problems because of poor blood flow to the brain. It is the second most common cause of dementia. We do not know enough about what causes it or how to prevent or treat the disease. It is also hard for doctors to tell the difference between vascular dementia and Alzheimer’s disease. So, we need to learn more about vascular dementia and find better ways to diagnose it.

Doctors currently use a mix of tests to tell the difference between vascular dementia and Alzheimer’s. These tests include looking at brain images (such as magnetic resonance imaging), collecting fluid from the spine (called a lumbar puncture), and memory tests. Although helpful, these tests can be misleading, which can cause an incorrect diagnosis. This is because some people with vascular dementia can look like they have Alzheimer’s. A lumbar puncture is also invasive and costly. So, finding a more accurate, simpler, and cheaper way to diagnose vascular dementia would be better. 

Work leading up to this project

For the past six years, Dr Philbert has been studying vascular dementia in human brains and has found that levels of sodium are higher in the brains of people who died with vascular dementia than those with Alzheimer’s disease (See Figure 1). This could help tell these two diseases apart. Now, we need to study if this happens in living people, and how/if this causes the disease to develop.

How will this work benefit people with dementia?

Dr Philbert will study sodium levels in the blood, fluid from the spinal canal (known as cerebral spinal fluid), and brain scans to learn more about vascular dementia. We know that current Alzheimer’s treatments have no real effect on people living with vascular dementia. However, these treatments may still cause side effects like feeling sick, tired, or having trouble sleeping. Therefore, an accurate diagnosis will not only help people understand their condition, but also prevent them from receiving unnecessary side effects and ineffective treatments. Importantly, being able to accurately tell who has a certain type of dementia will also lead to better treatments. This is because we can be more certain that clinical trials will include people with vascular dementia only and not a mix of dementia types.

Methods and techniques

The project will be divided into three main parts:

1. Sodium MRI scans: To see if sodium levels or patterns in the brain are different between these groups, which will improve diagnostic accuracy. MRI will be used to measure sodium levels in the brains of people with 1) vascular cognitive impairment, 2) early-stage Alzheimer’s disease, and 3) healthy individuals, with 19 people in each group. The scans will also look at brain size, blood vessel damage, and blood flow in the brain. Tests that measure blood and cerebrospinal fluid will help place people in the correct groups.
2. Is sodium linked to energy supply in the brain? Sodium levels are important, and our body has special ‘pumps’ to control how much goes in and out of our cells. Pumping sodium needs energy. However, these pumps may not work properly if there is a lack of energy. We already know that energy levels in the brain may be affected in vascular dementia. Blood, cerebrospinal fluid, and brain tissue will be used from the same people who have been imaged, to measure levels of important compounds that are related to energy. To measure this, Dr Philbert will use a method called mass spectrometry and hopes to understand if changing sodium in the brain is caused by altered energy levels. This will also reveal certain compounds that can be used to help detect vascular dementia in blood.
3. Blood vessels in the brain: These pumps might not be the only problem. A constant flow of blood to the brain is needed. This is because blood contains key nutrients (like glucose) that your brain needs for energy. We know that damage to vessels that carry blood to the brain can lead to dementia. Dr Philbert will research whether this damage to the vessels causes higher sodium levels in the brain. To study this, he will image the blood vessels in brains with vascular dementia using a powerful camera. This will reveal whether vessels in vascular dementia are more damaged than those in healthy brains. He will then use mass spectrometry to see if compounds in these damaged vessels are linked to sodium. This will help understand if a lack of blood flow due to damaged vessels in the brain also contributes to poor sodium control.

Dr. Philbert’s previous research has focused on using mass spectrometry to understand dementia. This method is powerful but can only be used on brain samples taken after death. To better help people with dementia, this fellowship will allow him to learn MRI analysis to study living brains.

If successful, the next step will be to move this sodium test from the ‘bench to bedside’. If our sodium MRI scans show promise in better diagnosing early Alzheimer’s disease and vascular cognitive impairment, we will conduct a larger study across multiple centres to confirm our results. We will then explore if this approach can be used in everyday medical practice. This will mean testing whether adding sodium measurements to routine MRI scans in people who start to show signs of memory issues can help distinguish between these groups. This will make routine MRI scans slightly longer but has the potential to improve vascular dementia diagnosis and, therefore, patient care.

The information collected during this project could help develop simpler and more affordable tests for diagnosing vascular cognitive impairment. The findings will also direct future research into the treatment of the disease. In addition, this research has the potential to create better models for studying vascular dementia. This will mean that scientists will not have to rely on people living with vascular dementia to study the disease.

The supervisory team

The University of Manchester is well-known for its excellent research in dementia and brain imaging, including MRI. Dr Philbert will work in the lab of Dr. Richard Unwin, a leading expert in dementia and mass spectrometry. He will also be guided and taught techniques by other members of his supervisory team. They include Prof. Laura Parkes, and Dr. Nils Muhlert, from our imaging theme and Dr. Ross Dunne, our dementia theme lead, who have considerable expertise in brain imaging and dementia diagnosis. Their combined expertise will provide Dr Philbert with the skills needed to achieve the goals of this fellowship and help him grow into an independent dementia researcher. Dr Philbert’s mentor, Prof. Garth Cooper from the University of Auckland, will help support his transition to scientific independence.

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