Neuropsychiatric symptoms of dementia: Q&A with Dr Byron Creese

Dr Byron Creese chose to pursue a career in dementia research after studying Psychology at University. His work focuses on the often under-recognised neuropsychiatric symptoms, such as hallucinations, which can cause huge distress in Alzheimer’s disease and other dementias. Around two thirds of people with Alzheimer’s disease experience these kinds of symptoms.

Byron’s work focuses on neuropsychiatric symptoms as risk factors for dementia, and aims to identify links between the disease and our genes.


Can you give us an overview of the work you do?

When people think of Alzheimer’s disease or other dementias, most think of symptoms to do with memory, thinking, planning and reasoning. However, a significant number of people with dementia also experience symptoms like hallucinations, suspicious thoughts, agitation and depression.

Examples of these would be thinking that their food has been poisoned, or that their relatives aren’t who they say they are, seeing people, animals or objects, or being very tearful or agitated. We refer to these as neuropsychiatric symptoms, and they can be hugely distressing and have a major impact on a person’s quality of life.

A major challenge of these symptoms is that we don’t have many effective treatments. This is a particular problem in treating psychosis, where there isn’t much evidence for non-pharmacological (non-drug) interventions, and the drug treatments we have are only slightly effective. These drug treatments also cause numerous severe side effects, such as Parkinsonism (shaking and unsteadiness). They also increase the risk of falls, triple the risk of stroke, and double the risk of death.

To develop new treatments, we need to understand more about the biology of these symptoms, and how they present clinically. To do this we have gathered a very large database of Alzheimer’s disease cases which have accompanying genetic data.


How did you get into dementia research?

I studied Psychology to Masters level until 2006. After university, I took a break from Science and worked in Finance for a few years. During that time, my Nan developed Alzheimer’s disease, which I suppose brought a career in science and research back to my attention.

In 2009, I began a PhD with Professor Clive Ballard, which was focused on psychosis in Alzheimer’s disease. A lot of the work we did at that time involved building up a big cohort of DNA samples from people with Alzheimer’s disease who had experienced symptoms like psychosis, depression and agitation, as well as those who did not experience any of these symptoms.

The kind of genetic research we do requires a large sample size – many thousands of samples really – so no single group can do this on their own and we are still busy setting up new collaborations to get more data.


Could you explain your Genetics research in more detail?

The first thing to highlight is that this is a highly collaborative project.  We have data from many thousands of people with Alzheimer’s disease from largely from the UK and Norway but also from Italy, USA, Greece, Poland, Finland, France…I think that’s all!

We take DNA samples from people with Alzheimer’s disease who have particular symptoms we’re interested in – these neuropsychiatric symptoms. We look across the person’s genome – the genetic blueprint for who we are – for variation. Variation across the genome is what gives rise to differences like hair or eye colour. We already know that certain variations are associated with an increased risk of disease and we want to know if there are any which are associated with neuropsychiatric symptoms. This could give us a clue as to why some people develop these symptoms and some don’t.

If there are any, we can work out if they’re nearby a gene. If that gene is of interest, we can do more work to investigate that, which could give us new research avenues.

We also use genes to look at shared genetic risk factors between disorders and conditions across the lifespan.

For example, in younger adults, you can have a condition like schizophrenia which is associated with psychosis, and then we see psychosis in older adults, and in dementia. One question we’re trying to answer is: is there any biological similarity between those symptoms? Are these symptoms caused by common mechanisms? What we discover about connections between Alzheimer’s disease and other conditions will also raise the possibility of developing new treatment options for people with Alzheimer’s disease and psychosis.


Are there any other projects you’re excited to be working on?

I’m currently involved in the PROTECT study – there we have a group of 25,000 cognitively healthy adults aged 50 and over. They’re assessed for these types of symptoms – depression, hallucinations, and we’re also conducting work to evaluate the significance of those symptoms in the development of later cognitive problems. The types of questions we’re asking are hallucinations in a cognitively healthy population associated with any sorts of memory impairments? And will that be useful in helping us predict who’s going to develop dementia? We can then integrate that info with genetics as well, to see if that can enhance the predictive value of genetics. This can helps us to predict more accurately who will develop symptoms, and at what point we can intervene. Examples of interventions could be social interventions, personalised care, or keeping people healthy for longer.


How do you feel dementia research is progressing?

There’s an increasing focus on neuropsychiatric symptoms in dementia. Soon we should have some new consensus criteria for psychosis in Alzheimer’s disease which will help establish a commonly accepted definition of what psychotic symptoms in the disease look like. Prof Ballard and I will be working on this as part of a group led by colleagues in Canada and the USA.

We’re seeing new treatments in the drug development pipeline, but I think there is an urgent need to develop treatments targeting novel disease mechanisms. What that means it that most drugs in development at the moment are ones that target biology of the disease that we already know about.  There are also a number of drugs in development for agitation and psychosis in AD which have shown efficacy in schizophrenia which brings those trans-diagnostic links I mentioned earlier into focus.

Non-drug treatments are also emerging, so things like exercise and social interaction. That’s definitely a good thing, as the side effects of commonly used anti-psychotics are quite severe.

Hopefully we’re getting to a position now where we can start to answer some questions about diseases mechanisms. Collaboration really is the key here and luckily we’ve found a lot of researchers willing to team up on this.

Next year we’ll have been gathering DNA samples from people with Alzheimer’s disease for 10 years – the collection we have now is one of the largest in the world. We’re on target hopefully in the next couple of years to get up to 10,000 samples which should allow us to take some big steps forward in this field. It’s quite unusual to have such a high number of samples with high quality clinical data, so we’re very lucky in that respect.

Follow Byron on Twitter @byron_creese to keep up to date. To read more about dementia research at Exeter, please visit our website, or follow #ExeterDementia.

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