How can we understand Parkinson's dementia better?

When I talk to patients who have Parkinson’s disease in my clinic, the one thing that terrifies them is that they could develop dementia. Their worries are not unfounded.  

Studies have found that nearly 50% of people with Parkinson’s disease will develop dementia within ten years of diagnosis. It's common to think about Parkinson's as a movement disorder. But actually, people with Parkinson's are six times more likely to get dementia than the general population. 

The problem is we don’t fully understand why this happens. In fact, at the moment, there are no treatments that change the course of Parkinson's. We've got good treatments that help with the symptoms, but they don't change the ultimate course of the disease. And if patients are beginning to develop dementia, we can't stop that either. 

That’s why I’m pursuing my current research.

To understand the disease, we must first have a better sense of what changes take place in the brains of people living with the condition. We can do this with the help of advanced neuroimaging. 

The aim of my research is to bring together advanced neuroimaging with measures of protein accumulation, or the build-up of proteins in the brain.  

The advanced imaging that I'm carrying out uses measures of brain connections and measures sensitive to brain iron. I'm also scanning using high-field MRI (or magnetic resonance imaging, used to form pictures of the body). This provides me with greater spatial resolution of the brain.  

I’m also using other approaches so that we can measure protein accumulation in the brain. To do this, I'm collecting blood and cerebrospinal fluid. I'm collaborating with chemists so that we can accurately measure the levels of proteins in people's blood and in their cerebrospinal fluid. Alongside this, I’m using PET imaging (or positron emission tomography, which produces 3D images of the inside of the body), which can directly measure particular proteins that build up in the brain. 

Ultimately, my aim is to be able to identify which particular combination of proteins is building up in the brain for each patient, so we can understand that person’s disease better.

As new treatments are being developed, knowing which proteins are building up – and understanding the changes in the brain early on before the disease sets in – will help us target the right treatments for the right people. 

The work that I'm doing will have wider relevance for other causes of neurodegeneration. My work is focused on Parkinson's dementia, but my findings will have applications for other dementias and potentially for other neurological conditions. 

I'm doing this research because, ultimately, I want to be able to slow the progression of Parkinson's dementia by targeting the right treatments to individual patients. I also want to bring some of the advanced imaging measures we are using in my research into clinical pipelines, so that we can monitor disease progression in patients who are seen in the clinic. 

My aim is that one day, when I’m seeing a patient in my clinic, and I'm worried they're developing Parkinson's dementia, that I'd be able to say to that specific person: 'Well, you have this particular pattern of changes. So this new treatment that's been developed would be right for you.'

As well as doing advanced imaging – using two different MRI scanners – I'm also using PET imaging, measures of proteins in the plasma and cerebrospinal fluid and also MEG (magnetoencephalography, which measures or maps brain activity through magnetic fields generated in the brain). Together, these different modalities will provide information across a range of spatial scales. I will do this in people living with the condition to address the same question: how does dementia happen in Parkinson’s? 

All this is possible because of Wellcome’s Discovery Research Career Development Awards. The award has allowed me to be ambitious about the questions that I'm asking and think much more broadly. 

Wellcome funding allows me quite a lot of flexibility and that's what's really attractive about this award. It allowed me to apply for it as a clinician and as a scientist. It was flexible in terms of time – this is an eight-year project – and it's also flexible in terms of the questions that I'm asking. 

Through discovery science, I am able to work on this really important research question that addresses the real-world problem of Parkinson's dementia. Hopefully, this work can ultimately help ease some of that worry among patients by helping to target the right treatments to the right patients at an early stage in their disease progression.