Be Part of Research: Dementia

• Dementia is one of the main causes of death in the UK and it regularly makes the headlines when high profile people choose to share their diagnosis or when there are new findings of possible causes.  In this episode, we talk to  Professor John O’Brien who is the NIHR Speciality Lead for Dementia and Professor of Old Age Psychiatry. We explore why dementia rates are increasing, what research has found so far and what research is being done currently to improve diagnosis, treatment and care. Visit shownotes and transcript.

Transcript

Dementia podcast transcript

Professor Turi King:

Hello and welcome. You are listening to the Be Part of Research Podcast. I am Professor Turi King, your host and today’s podcast is about dementia.

Dementia is one of the main causes of death in the UK and it regularly makes the headlines when high profile people choose to share their diagnosis or when there are new findings of possible causes.

There are currently around 900,000 people living with dementia in the UK and this is set to increase to over one million by 2025.

Although age is a risk factor dementia is not an inevitable part of ageing.

Joining me today is Professor John O’Brien. He is the NIHR Speciality Lead for Dementia and Professor of Old Age Psychiatry.

So, John, let’s start at the beginning. What is dementia? Can you tell me a little bit about the different types of dementia?

Professor John O’Brien:
Yes, well dementia is a general term that we use that really covers a number of different diseases that all cause problems with thinking, memory and with the ability to undertake daily activities.

The main cause of dementia is Alzheimer’s disease and I think many people will be familiar with that term and that is responsible for about two-thirds of cases but there are other important causes of dementia as well that are sometimes less talked about.

One of those is vascular dementia which is when blood vessels in the brain don’t work properly maybe after a stroke but sometimes in the absence of a stroke and have a sort of vascular cause of dementia.

There’s a syndrome called dementia with Lewy Bodies which is a condition that has some relationship to Alzheimer’s disease but also some to Parkinson’s disease so it not only affects the ability to think and to remember but also can affect movements as well so people can be slow and have difficulty walking and sometimes have a shake.

And there’s a condition called Frontal dementia or Frontal temporal dementia to give its  fuller title which affects the front part of the brain and then people have difficulty with planning activities, with judgements – social judgement and also with language and those four main types of dementia: Alzheimer’s disease, vascular dementia, dementia with Lewy bodies and Frontal temporal dementia account for more than 90% of cases of dementia.

Turi:
And I understand that dementia rates are increasing so why is that?

John:
Yes, well that’s another great question – so they are and that’s largely because we’re all living longer which is obviously very good news. 50 years ago life expectancy was only in our 60s and now it’s in our 80s and rising so that is tremendously good news but unfortunately, conditions that are more common as we get older and dementia is certainly one of those will become more common as a result and so the reason dementia is increasing is really simply because we are living longer. There aren’t any other real reasons why dementia is increasing, in fact, because of some changes we’ve had to sort of lifestyle and medical treatment there is some evidence that dementia is slightly less common than it might have been if we hadn’t had those advances.

So, if you project what dementia would have looked like from figures based 30 years ago to now, we’d actually expect a lot more cases of dementia now than we currently have and that is, we think, largely due to improvements in lifestyle, things like control of blood pressure, things like better treatment of stroke and things like that as well as perhaps better education which is also a sort of a protective factor against dementia.

Turi:
So, although there are lots of theories about you know social interaction and air pollution and high impact sport, are we any closer to finding out what causes dementia?

John:
Yes, well these things like air pollution they hit the headlines and everyone sees them because they are newsworthy and topical but actually there have been major strides over the last 10-20 years in understanding the causes and mechanisms of dementia and all the dementias that I mentioned, particularly Alzheimer’s disease, Lewy Body dementia and Frontal temporal dementia they share something in common which is the main cause of them is…is abnormal lay down of proteins in the brain of different type and these are proteins that are normal for brain activity, we all need them but because of either producing too much of them or not getting rid of proteins as we should, particularly when those proteins have had their use and need to be disposed of, if they cumulate in the brain they get laid down in nerve cells, they affect the functioning of those nerve cells and ultimately those nerve cells will die and really that is at the root cause of what is the problem of dementias.

Now, one reason that age is a big risk factor for dementia is the longer we live the more we’ve had to produce these proteins and also the less efficient we are at getting rid of them. As well as that, the processing of these proteins is affected by our genes, our genetic make up but also, and this is coming to the point you raised, it is also affected by a sort of lifestyle factors and now there are 12-15 different lifestyle factors that seem to either accelerate our risk of getting dementia or indeed sort of perhaps protect us from getting dementia.

And the relationship between those and the mechanisms is not entirely worked out as yet but it is a very important area of research and things that you mentioned like air pollution, social stimulation and there are also other things that are protective like exercise, I mentioned already control in blood pressure and diabetes, they are all very good things and there are things that we can do to help reduce our risk of getting dementia but it might not stop it altogether. These are things that will help to reduce our risk but won’t necessarily prevent us from getting dementia.

Turi
So, moving on to research, what are the main areas or themes in dementia research these days?

John:
Well, it’s very broad and the UK is a great place for dementia research. We frequently come in the top, you know, two of countries behind the US usually because of their greater kind of critical mass and volume but there’s a breadth of research here that surrounds the mechanisms of disease, you know what causes the different types of dementia around the diagnosis of it. How do we diagnose the different types? How can we diagnose that earlier through to different treatments? How can we treat the condition and that isn’t just about you know drugs or pharmacology, it’s also about other strategies that might help?

I talked about risk reduction but there are also other things that might be…might be helpful through to looking at care. How can we better care for people who have dementia as they progress through their dementia journey, through to end of life issues. How can we ensure that the transition there and the care at the end of life is really optimal for people with dementia? So, it’s really very broad. And that research is supported by the NIHR which at any one time supports around 150 studies in dementia across that wide range of activity.

Turi:
Obviously, the UK is one of the centres really it sounds like for dementia research. So, what have been the key research findings over the last five to 10 years then?

John:
Well, it’s hard to summarise them briefly so I can only just highlight a few really that I think are particularly important. One is, I think the genetics so I mentioned that before but we are discovering more and more about some genes that increase our risk of different diseases. Mainly around Alzheimer’s but there is increasing their work in some of the other dementias.

So, the team in Cardiff, for example, has been leading that work and we now think there are around 70 genes that increase our risk and they are useful because we can look at which mechanisms they might be involved with. Some are in the trafficking of proteins that I mentioned but some are in other areas like inflammation which is emerging as a very important potential mechanism that we can look at in dementia.

So, there’s genetics, there’s the risk factors that I talked about and there have been a number of studies that have been very, very important there.

The other thing is how to use our current treatments better. So, we’ve got four licenced treatments for dementia in the UK or for Alzheimer’s disease and there was a study, the Domino Study, that was supported by the National Institute of Health Research, the clinical research network played a very important role in delivering that study and that showed two things really.

One was that use of these drugs was effective even in people at the more severe stage of dementia so previously we used to stop these drugs when people reached the more moderate stages and the study clearly showed that people benefitted throughout the course.

And secondly that two drugs were better than one so a combination of these two agents was more effective than one on its own and both of those things have now led to changes in clinical practice, not just in the UK but worldwide and so it has been very, very important in how we manage people with dementia today.

Turi:
So, I’m really struck by just how broad the studies are. Everything from genetics through to sort of treatments and how we make that better. It’s incredible. It sounds like fantastic research.

John:
Yes, I think there’s a lot more we need to do of course but I think it is and it is really important because we need research that helps people today at different stages from early diagnosis through to the later stages. We need to understand better how to support people, how to manage people now but of course looking to the future we want treatments that are going to modify the disease and ultimately, we want to try and prevent cases of dementia. You know Alzheimer’s disease and the other dementias. So, it’s really crucial that we do have research that spans the whole spectrum and that is what the National Institute of Health Research supports is research across that whole spectrum of studies in humans.

Turi:
So, you’ve talked about these changes in treatments. Are we making progress then in how we can kind of treat the disease?

John:
Yes, I think we are. We don’t yet have a disease modifier in the UK but there has been tremendous progress and people may have heard about one particular drug, Aducanumab, which is a drug that…it’s actually an immunotherapy so this is something that is actually injected and its aim is to lower levels of amyloid in the brain and that drug has been shown in studies to have good effect at lowering amyloid levels in the brain and in this country we played an important part in delivering that study through the NIHR and Join Dementia Research as well.

And what those results showed was that although amyloid levels were lowered significantly in the brain, the clinical benefit of that wasn’t quite definitive. Now, it’s been enough for some regulators, particularly in the UK, the food and drug administration there has given a provisional licence for its use, but regulators when they looked at that in Europe decided that the evidence wasn’t quite there.

So, although we don’t have that as a drug at the moment, I think it was a very important proof of principle that these studies can be done and that we can get good readouts and the evidence base was there for the regulators to then make their appropriate decisions. And there are a lot more studies ongoing so we have other studies ongoing at the moment that are recruiting participants, looking at ways of lowering amyloid but also moving on to other proteins that are involved in particularly Alzheimer’s disease.

So, there is one called tau so there are anti-bodies against that to try and lower the levels of tau in the brain and also some new approaches based around inflammation so trying to activate some of the inflammatory cells in the brain in the hope that might reduce these abnormal protein levels. So, I think there are a lot of exciting studies underway and in prospects. Although we don’t have one yet I don’t think the future has never looked sort of brighter from that point of view.

Turi:
I think it’s also the way science works, isn’t it? It’s the tiny little incremental steps slowly, slowly moving forward and learning ways that we can start to treat the disease to some extent.

John:
Yes, absolutely and that’s gone hand in hand with what’s also needed which is better diagnostics to be able to actually identify people at an early stage when we can give these treatments so there’s been a lot of progress there in brain imaging methods looking not just at the loss of brain structure that we see in dementias but looking at some of the abnormal proteins that we can now visualise using brain imaging as well as a very exciting in the last couple of years the prospect of blood biomarkers. So, something from a blood test, that will give some indication of whether people are likely to have abnormal protein levels in the brain and I think that combined with some of these new therapies will be very important for future dementia studies.

Turi:
It’s really exciting stuff. What’s next for dementia research then?

John:
Well, it’s always dangerous isn’t it trying to look into the future but I think our current direction is probably where we are going to go so one thing we do need is an increase in the volume of dementia research. We’re doing a lot as we highlighted but we need to do more and we know that dementia research is less developed than other areas, for example, areas like cancer which are equally important, have about four time the volume and four times the funding that we have in dementia.

So, we have grown dementia research a lot but we’ve got to grow it much further so that’s very, very important. We need to attract more researchers into the field so that they can deliver those studies and develop new approaches.

So, that’s sort of in general terms, in more specific terms, I think that as we understand the mechanisms of these different diseases better we will be able to target treatments towards those mechanisms and I think we already know that dementias are certainly not simple, they are complex disorders but they often involve several different processes, not just one so I talked a little bit about amyloid, a little bit about tau and a little bit about inflammation but it might well be we need a combination of approaches to be able to really tackle these diseases so I think that will be a feature of future research and there’s also a need to better understand how we can do clinical trials so, for example, the use of technology, the use of remote assessments, the use of different markers to allow us to try treatments better and rather than the current dementia studies which sometimes take two or three years, we would like to have studies where we can understand in a much shorter time if these potential treatments are actually going to help people or not.

Turi:
So, what’s clear for that is if you’re saying that dementia research needs to grow, part of that is having people taking part in the research.

So, for people listening who may want to get involved can you explain a bit about the different types of studies that people can get involved in.

John:
Yes, well as we talked about there’s a very wide variety of different studies so when people think about dementia research they sometimes think about drug studies or studies like that but as we said the range is really very, very broad so there are studies looking at people’s experiences of dementia, the online surveys, telephone surveys, focus groups. There are studies about care and different types of care. There are studies that involve looking at some of the blood biomarkers, maybe some of the brain scans, looking at the diagnostics. Sub-cognitive tests so we have studies looking at the place of virtual reality, for example, as a very early diagnostic test and then we have studies of the actual treatments themselves and people’s involvement in research depends very much on the study itself. Sometimes it’s a one off interview assessment or a questionnaire online. Other times it’s much more extensive and would involve coming to a research unit or a hospital for assessments and that might go on for two to three years and depending on the length of the study. So, it’s highly variable and very much dependant on the sort of research people would like to take part in.

Turi:
So, what might they be expected to do if they are accepted on to a study?

John:
Well, it depends very much on the type of study because they are very broad in type. So, some studies might involve something as simple as filling out a questionnaire or filling in an online survey or taking part in a telephone interview or attending a focus group.

Others might involve coming up for a test of some sort. That might be a blood test or it might be a brain scan or something like that. Usually combined with a clinical assessment so maybe some questions, maybe some memory tests, a bit like a hospital clinic appointment but this would be for research purposes.

Other studies would involve being asked to take a tablet perhaps or an injection or even come up to the hospital for an infusion, it might take half a day or something like that and that might be repeated every…every few months.

So, studies really range from a single assessment that might be a virtual assessment or a postal one or a phone call through to studies where people might be asked to come to the hospital several times over a year perhaps to have a repeated assessment and repeated scans over a couple of years. So, it’s really quite varied.

Turi:
And I suppose with each study what you do is you are talking through the participants what you’re looking at and how you are doing it and it’s all completely up to them in terms of what they want to take part in, isn’t it?

John:
Absolutely. So, the first stage of research is to let people know about what’s going on and that’s really, really important and that’s where systems like Join Dementia Research can be very, very helpful. Participants are given full information about the study and I think it’s important people who are interested in taking part really you know look at that and ask questions: what does the study involve, what is the commitment, is it realistic for me to take part in that? Do I want to take part in that? What are the possible benefits of taking part and what are the possible risks and harms of taking part?

People will always get a written information sheet that gives full details. It is important to look at that, to discuss that if they wish with family and friends to make an informed decision and then people will be asked to sign a consent form to take part in the study.

And it’s important also to realise the consent form isn’t…it’s not a legal agreement you have to take…it’s an indication that you understand what the study is about and you would like to take part and if people want to change their mind at any point in the research process they are absently free to do that.

Turi:
So, patients really are the lifeblood of a lot of the research that people do. So, if people do want to take part in dementia research how can they do that?

John:
So, the best way is through what’s called Join Dementia Research. People can sign up to this online or through the dementia charities who support that which is Alzheimer’s Research UK, the Alzheimer’s Society and Alzheimer Scotland. Join Dementia Research is run by the NIHR. If people want to find it online the quickest way is to type those three words into a search engine, Join Dementia Research, and you will find it.

Participants can sign up themselves or they can ask somebody to sign up for them. What that does is it enables people to join a register which then allows them to find out about what research studies are going on in their area. It also allows them to be matched to studies so that researchers can then contact them if they might be suitable for studies.

And again, as mentioned there is a huge variety from sort of these online studies to more intensive studies. Anyone over 18 can sign up. Over 50,000 people already have and over 60,000 people have actually taken part in studies through Join Dementia Research.

We particularly would like more people with dementia and cognitive impairment to sign up for studies, all types of dementia but also other people, healthy people are very welcome and there are studies for everyone.

Turi:
If there was one thing that you wanted people to remember from this podcast what would it be?

John:
I think it’s that dementia is a huge problem and a growing problem but it’s not an insoluble or hopeless problem and great strides have been made in terms of research, in terms of understanding the disease, you know diagnostics and in terms of new treatments although there is much more to do.

So, I suppose the key message is that dementia is a huge challenge but the prospects of new treatments has never been closer and I think through research we will and can make progress. So, please do you know consider taking part. We mentioned Join Dementia Research, please encourage other people that you know, particularly those who have dementia and cognitive impairment to take part and I think through research we will make progress.

Turi:
John, thank you so much for sharing your insights into dementia research. It’s been incredibly fascinating.

We hope you enjoyed listening. If you’d like to read the show notes for this episode or listen to the other podcasts in this series visit bepartofresearch.ac.uk.