In the first of a new series introducing some of our Newcastle BRC academic and clinical researchers we talk to Professor John-Paul Taylor, Deputy Dementia Theme Lead for the BRC. John-Paul is a Professor of Translational Dementia Research with the Institute of Translational and Clinical Research at Newcastle University and an Honorary Consultant in Old Age Psychiatry with the Cumbria, Northumberland, and Tyne and Wear (CNTW) NHS Trust.

John-Paul specialises in understanding the causes and symptoms of a particular type of dementia: dementia with Lewy bodies (DLB), also known as Lewy body disease. DLB is the second most frequent cause of age-related neurodegenerative dementia with at least 10-15% of older adults with dementia thought to be living with this little known but not uncommon disease.

Lewy bodies are deposits of abnormal proteins inside brain cells and are named after Dr Friedrich Lewy who first discovered them under the microscope in 1912. Lewy bodies are associated with the death of brain cells and subsequent deterioration of the brain. DLB symptoms include problems with memory, concentration and other cognitive abilities as well as potentially difficulties with balance, movement, sleep and autonomic functioning (bladder, bowel, blood pressure control).

What drew you to the field of Dementia research?

I studied for my PhD as part of an intercalated medical degree and was actually focused on paediatric neuroscience at the time. Although I loved working with children, I also did some placements working with older people and came to realise that I was most interested in Psychiatry in older adults and – as an extension of this – the neurodegenerative diseases that cause difficulties for the elderly population. This is an area of huge unmet need and there is significant opportunity to undertake research that can make a real, practical difference to peoples’ lives. This is why I ended up focusing both my clinical and my research career in this field.

What are you currently working on and what question or challenge were you setting out to address when you started the work?

My research is focused on how we can improve the rate and accuracy of diagnosis of dementia with Lewy bodies (DLB), as DLB is often mistaken for other forms of dementia. I am also working on new ways to manage and treat the symptoms of the disease. My research is very much based in clinical practice, which allows me to focus on the patient experience of DLB and what symptoms they find most difficult to live with, so that I can direct my research to the areas that will bring most benefit to people.

I currently have Newcastle BRC funding to look at the cholinergic system of the brain – a vital neurotransmitter system that produces Acetylcholine (ACh); ACh is a chemical messenger that helps govern our attention, thinking abilities, and memory. We already know that the cholinergic system is strongly affected by DLB and although there are existing treatments that help with the symptoms caused by this, there’s scope to improve how well they perform.

The most successful treatments for dementia to-date have been drugs that aim to boost the production of ACh in the brain – they aren’t cures, but they can improve a patient’s experience of the symptoms: hallucinations can get better, fluctuations in cognitive ability can improve, feelings of apathy are reduced and patients find they have more motivation and better memory function. Unfortunately, some patients do not respond well to the current treatments and even for those who do, the effects may not be sustained. What I’m looking to discover is if we can create a longer or deeper window of improvement in these symptoms for patients by finding better measures to tell us how well the cholinergic system is working, so that we can identify and apply new treatments to improve its function.

Is there a benefit to being diagnosed earlier for DLB patients?

DLB overlaps with Alzheimers, but it is a different condition and therefore patients may experience side-effects from taking drugs intended to treat Alzheimers. Having an accurate diagnosis early on is helpful for planning effective treatment, prognosis and long-term care. We still face the challenge with DLB (as with all dementias) that there are no disease-modifying treatments, or a cure, as yet. But better understanding the diagnosis and making it earlier allows for patients and their families to plan for the future and identifies people who could participate in upcoming clinical trials that are looking at therapies and treatments that could slow the disease’s progress.

Can you tell us a bit more about where your work fits in to the broader field of dementia research?

In Newcastle we benefit from having a critical mass of researchers in the field of dementia broadly, but also specifically in DLB research – Newcastle University was ranked as the top institution worldwide for expertise in DLB in a review by Expertscape last year.

The research here in Newcastle spans fundamental science, through translational medical research – where I sit – and on into clinical practice, working with actual patients.

At the basic science end, we have excellent scientists looking at things like how we can improve our understanding of the brain’s neurotransmitter systems, what causes Lewy bodies to form and how this might be connected to mitochondria (the mini-power stations which help provide energy forour cells). Other research looks at using advanced neuroimaging techniques to understand why certain LBD patients get certain symptoms, like hallucinations or fluctuating cognitive abilities. And then in the clinical space, we have clinician scientists who are working on developing better techniques to diagnose patients earlier on as well as helping patients to manage their symptoms.

As BRC Deputy Theme Lead for Dementia, I’m interested in fostering a broader research endeavour in the field, growing our capacity, drawing on these different types of research and encouraging collaborations that can produce new ideas and approaches.

What do you predict as being the next major breakthrough in this area?

Optimistically, there is now a huge amount of activity looking at potential new therapeutics. In a current project that we are collaborating on with Cambridge and Exeter Universities we are conducting an exercise to identify whether any existing drugs can be repurposed for use in DLB either to alleviate symptoms or even affect the underlying disease itself.

The BRC has many research themes, do you feel this has been useful for you in carrying out your research?

Being part of the Newcastle BRC has opened up a host of opportunities to cross-fertilise my research, often prompted by informal ‘corridor’ discussions as well as through more formal strategies to encourage cross-theme working. Within the Dementia theme, we’re about to start trials for a highly novel agent, which has arisen out of the Liver theme around ‘brain fog’ symptoms in Non Alchoholic Fatty Liver Disease patients, which closely resemble symptoms experienced by Parkinson’s disease patients. We’re hopeful that trials will show that this treatment also improves the symptoms of Parkinson’s disease patients, if not actively working to modify the disease itself. We’ve also seen some exciting work coming from colleagues in the Neuromuscular Disease theme, where they have identified that patients suffering from a mitochondrial dysfunction seem to develop Lewy bodies; this suggests that the mitochondria potentially have a role to play in DLB. And finally, a colleague working in the Skin & Oral Disease theme has been looking at whether skin biopsies might reveal the presence of the alpha-synuclein protein (present in patients with DLB) at an early stage before it becomes apparent in the brain.