Podcast – 2019 Roundup Christmas Special

Voice Over:

Welcome to the Dementia Researcher podcast, brought to you by dementiaresearcher.nihr.ac.uk, a network for early career researchers.

Adam Smith:

Hello, as it’s Christmas, when we’re saying goodbye to 2019, we’ve cut together a few of our favourite moments from this year’s podcasts, or what I should say is poor Patrick the sound man has, who had to listen to all the episodes we’ve put out this year to pick out our favourite moments. We hope you enjoy this episode almost as much as Patrick enjoyed making it.

Thank you to everybody so much for listening to us this year and helping us reach over 3,000 players every month. We’ll be back to you in the New Year on the 6th of January, which happens to also be my birthday, when Anna Volkmer will be talking to a panel about study participant consent.

So, thank you very much again for listening, and Merry Christmas.

Aoife Kiely:

Hello, my name is Aoife Kiely, and I’m a Research Officer for Alzheimer’s Society. I’m pleased to be co-hosting this podcast recording for the NIHR Dementia Researcher website.

Adam Smith:

Hello, I’m Adam Smith. And I’m delighted to be hosting this podcast recording for the Dementia Researcher website.

Anna Volkmer:

Hello, my name is Anna Volkmer and I am delighted to be hosting this podcast today for the NIHR Dementia Researcher website.

Lakshmi Mendez:

My name is Lakshmi Mendez and I’m an NIHR Research Project Coordinator based at University College, London.

Katie Stubbs:

Hello, my name is Katie Stubbs and I’m a Communications Officer for Alzheimer’s Research UK, and I’m pleased to have been invited to host this podcast for the Dementia Researcher website.

Speaker 7:

Hello. Social media. Is it a real benefit helping to create a global community of shared ideas, fostering collaboration and cross-country partnership, bringing closer the Utopian vision of a world united by beautiful science and the pursuit of knowledge and truth? Or is it just another thing to add to the already long list of early career researchers’ things they’re being asked to do? Fellowship writing, conference attending, poster making, presentation giving, networking, mentoring, career development, healthy eating, going to the gym, podcasts.

Speaker 8:

I’ve done another presentation since, and I’ve called it, Why Usain Bolt Shaves his Legs, and really what the key message was that there’s about 50,000 people in the UK doing a PhD in Biology. And the traditional way to get to academia is you do a postdoc, then you do two fellowships, and then you get to a tenure position. So there’s 50,000 Biology PhD students, and there’s about 200 Junior Fellowships given out each year. So it is incredibly competitive.

Anna Volkmer:

Depressing.

Speaker 8:

So I said in this talk that we’re basically in the Olympics of Academia and at the highest level, you’ve got to do the running and you’ve got to the weightlifting and that’s winning grants and publishing papers, but you also need to shave your legs. You need to have that every millimetre counts. And part of that is just being known. Is your face being known by the Review Board? I talked about a study where radiologists were actually better at their job when you stapled a photograph to the front of the document, and just seeing that face meant that they looked at the X-rays in more detail.

Anna Volkmer:

Do you think that’s true for CVs though? Because having CVS come through, I am put off when people include a photo of themselves on their CV. Maybe that’s a personal thing.

Speaker 8:

Yes. No, I think that’s a UK thing.

Anna Volkmer:

Yeah, I think that’s a UK thing. [crosstalk 00:03:31] Arial font, full title, done.

Speaker 8:

I go comic Sans obviously. Just kidding.

Anna Volkmer:

But you know that was developed so that the “a” is how you write an “a” normally so that children can understand it when it’s written.

Speaker 8:

Yeah it looks like a child’s handwriting that’s why people don’t want it on their CV. [crosstalk 00:03:51] Anyway.

So not a photo but like a handshake or a senior tweet showing a bit of personality. If they know you’re a human being, they’re more likely to review your grants better in future, just get over their heads.

Aoife Kiely:

You work on an outside research UK project that is led by professor Kevin Morgan. And as you said already, you’re generating the genetic data from the BDR tissue, but I know you already have quite a large DNA bank already. So what kind of additional benefit is adding the BDR samples to that?

Speaker 17:

As well as increasing sample size for statistical purposes, the BDR is unique as Kirsty was just saying, and the fact that we have so much clinical data. So part of the reason why we have so much background noise when doing genetic analysis with complex diseases, such as Alzheimer’s disease, is because there is varied variation in the endophenotypes. So with all the detailed clinical and pathology data we have from the BDR we can correlate genetic polymorphisms with those endophenotypes rather than the disease and it becomes a clearer finding.

Aoife Kiely:

And also, because as well as kind of doing all the sequencing, I understand that you are also kind of feeding that genetic information back into the BDR cohort as well.

Speaker 17:

Yes. Yeah. So yeah, I think that’s now available on the GPUK and I think it’s also in the brain bank as well.

Aoife Kiely:

Yeah. And I think that’s a great feature of BDR as well, that it’s not just the brain tissue that you’re getting, but you can get all the components of the tissue like DNA, RNA, and CSF. I think a lot of people don’t realise that.

So if you were talking to a fellow researcher who wasn’t sure whether brain tissue was for them or they thought it was too complicated or wouldn’t be any help to their research, what would you guys tell them?

Speaker 17:

I would tell them that is very incorrect. I think human tissue is extremely valuable to any type of researcher working with dementia. This is what I preach a lot of the time to the biochemical and the animal models of cell culture people who we come in contact with at conferences and in our university.

I’ve a really good example of this. Actually, we just have a fantastic new research associate working with us, Dr David Cross from Aberdeen. And he has worked for 10 years plus in animal models. And he was flabbergasted when he finally saw the true disease in human tissue. He saw amyloid beta for the first time that wasn’t from an animal model and he couldn’t believe how different it was. Now, that’s someone who studied this in depth for over 10 years and tau as well. But it was, I remember his face with the amyloid.

So I think it’s really important that they do amazing work, they do things that I could never do genetic, transgenic mouse and amazing cell models, but it has to relate to the human model because that’s what we’re trying to do. And it’s so simple to get BDR tissue. You literally… If you have no idea what to do, you just email the BDR coordinator and tell her what you want and she will signpost you directly to the brain bank that can help and is literally filling out one form. That’s all it is. It’s so easy and it’s relatively cheap as well, but it can give you so much value to your animal models cause you relate the translation of it into the human model.

Anna Volkmer:

The majority of research so far has concentrated on objects as comforters, particularly in relation to dementia and ageing. So research has looked at the objects that make a room look familiar, the cover, a small piece of furniture, pictures, photographs, things like that. The functional objects, as we’re talking about, if I make clear what I mean by the functional objects, because obviously any object has a function. But if we look at things like a kettle, we can take action. So I don’t have to wait for the 11 o’clock trolley to come around. I can make my own cup of tea when I want my own cup of tea, the way I like my cup of tea. I could have it in my own cup rather than the care home cup that everyone else has used.

And I might have a cup that I have. I know I have a cup that I have for tea and a cup that I have a coffee. I don’t know why, it makes no difference, but for some reason, to me, it does. So these are the objects that I’m talking about within the home, a Hoover, a duster, having these things that you have access to carry out a task.

So in relation to care homes, they have staff employed to do those things. So I think because staff are employed to do them, that creates a barrier. Because if I allow you to do it, then what am I doing? Do I look like I’m not doing my job? Am I then in a difficult position because I have to, then… I could be questioned about what it is I’m doing and what I’m not doing. Equally if somebody has an accident, then is that my fault? So what I will do is I won’t allow you to use things because every object is seen as a potential risk.

Speaker 9:

I was going to say the kettle one, obviously boiling water. That’s not… you immediately think risk, don’t you? Yeah. But I guess you have to balance the change to their lifestyle, not the change of their lifestyle, but the benefit to their lifestyle.

Anna Volkmer:

It’s interesting that you say you look at a kettle you immediately see risk. I mean, why is that?

Speaker 9:

Because I have an eight-year-old at home.

Anna Volkmer:

But this lady will have been living in her own home for the last 70 years and making cups of tea, too many to ever count. Because she’s changed her environment that simple task of making a cup of tea is suddenly deemed too risky for her. And I think what Kellen is perhaps saying is an exploration of where does that mindset of the instant perception of risk come from in what is in effect a normal household object.

Speaker 9:

Yeah. I guess you have to remember that they’re individuals coming with a background of managing their own risk every day.

Adam Smith:

I’m Adam Smith. And today I’m hosting this special podcast recording from day two of the outsiders association international conference currently taking place in Los Angeles. What are we going to talk about first? Should we start? What about last night’s welcome reception, which was fantastic, right? I mean, there must have been so much work going into organising that. For those who didn’t know, it was at Universal Studios.

Speaker 9:

4000 people.

Adam Smith:

4000 attended in the end. Wow. And they all had to get coached from the hotels to the place, which explains the… The queues were long. Right?

Speaker 9:

Yeah. I heard that they were over a hundred minutes long near closing.

Adam Smith:

What do you mean you’ve heard? You didn’t go.

Speaker 9:

I didn’t, but I got reports.

Speaker 10:

You didn’t go.

Speaker 9:

I didn’t.

Adam Smith:

Free food and drinks and Harry Potter rides.

Speaker 9:

I know. Well, it wasn’t. I have a lot of friends in LA and I am trying to squeeze it and seeing this one. So I chose to go have dinner with them.

Speaker 10:

I won’t lie. I would choose Harry Potter over my friends.

Speaker 9:

I know perhaps I missed out. I missed the Jurassic World ride, which sounded epic.

Speaker 13:

Oh no. I think it was a fantastic day. I love that there was a range between these neurodegenerative conditions. And one thing I do wish was that there were more members of the public there. And I think it’s important to know, because some people ask me when I tell them about the symposium, that a lot of these talks are free and that it’s not like you’re in a room of people who judge if you ask a question and everyone really explained thoroughly. So I think that there’s some stigma that sometimes these sorts of talks are just for academics and people will understand. But I think that if more members of the public got engaged, got in contact or just emailed some of the people that they see. Like, we’re kind, we want to talk about this because it’s important, but I think those people missed out.

Speaker 11:

Jack, Marianne, when you’re preparing your fellowship applications, what kind of process do you go through to…

Marianne:

It should be quite down to the wire sometimes with applications, for any kind of funding really. I had at least had experience of preparing grants for senior faculty members within my research fellow role at the university before I applied for my fellowship. But when, when you’re applying to a fellowship like the NIHR or something like that, having a coherent body of work that can be looked at over a protracted period can be quite important. And because there’s not a huge amount of research looking at specifically eyesight in people with dementia it’s all quite new stuff.

And so there wasn’t enough stuff to really put together a three year program of work. Because if it’s something new, you don’t know whether it’s something that is worth doing three years’ worth of research on. So when Fight For Sight announced this one year primer fellowship award jointly with the Royal Society of Medicine, I thought, “Oh, actually I could apply for that and do a exploratory project to look to see whether this is something that could become more research in the future, see whether it’s actually worth pursuing or not”. And so it was the first fellowship that I’d applied for, but I had to wait for the right kind of opportunity to come along to suit the research idea that I had.

Jack:

I think for me, I’ve researched it… Preparations that people sometimes forget to think about is actually talking, because you don’t want to write up 2,000 words, 5,000 words on a bad idea, and there’ll be senior people in your university who are on these panels, who know what a good idea and a bad idea is.

And there’s certain unspoken landmines, which are bad ideas that if you include in your fellowship, your fellowship will go into the bin. And sometimes are explicitly stated. ARUK has one where if you use high dose amyloid in cell culture, we now know that the doses, the concentrations don’t reach that high in the brain. And so putting high dose on cells doesn’t make any sense. And that’s a landmine, you’ll go in the bin. So write down 10, 15 ideas, which you’ve got some pilot data for early, well before the due date, and then go talk to these senior people and they’ll tell you the good ones. They’ll tell you the bad ones. And then you can aim to get more pilot data for the good ideas, which you can then construct a really good application from.

But it does seem, as Marianne said, it does seem to go down to the wire in the end any way. So no matter how prepared you are, I ended up on the phone to the accountant. It’s 7:00 PM because I didn’t know that it required a third approval step, so a pre=approval an at-time approval. And then…

Anna Volkmer:

And sort of the loop back around to what we were talking about at the beginning. You’re both lecturers, but you obviously have research interests. How does it work in your job? Are you a lecturer who does research on the side? Are you a researcher who teaches, how do you feel your time is split?

Speaker 14:

I think it’s, it’s combined. I’m heavily involved in what’s called the ideal study, which is our big cohort study, looking at living well with dementia. And that study has been running since 2014. And I was actually employed as a senior research fellow on that. I am still actively involved in that study, still working on papers from that. So I have to say that having switched it is a bit of a challenge to balance your time. I think anybody new to that position regardless will always say that.

So it is a challenge to balance your time, but I enjoy teaching as well. So it’s not like… It is sort of an enjoyable activity. It’s also, I think you’re not going to get good research ideas by just sitting, staring at a computer.

For me, research ideas, come from talking to people and even engaging with the students that I’m with at the moment. I’m learning things that’s quite fascinating. And that starts to trigger in my brain ideas about research.

Anna Volkmer:

I was going to say, actually there was that big ad campaign for secondary school teachers and they showed kids just asking these questions that you sort of wouldn’t ask yourself. You’d forget how to ask those questions. Cause you’re so focused on something so to have someone ask a more simple question, you might go, “Oh yeah”.

Speaker 14:

See it just sort of triggers. And I think that’s… I think it’s interaction. As I say for me, that’s the benefit. That’s why we love doing both.

Speaker 12:

And the cohorts that DPUK brings together. They’re not dementia cohorts are they?

Speaker 13:

No, absolutely. We’ve got birth cohorts. We’ve got cardiovascular focus cohorts. We’ve got healthy population cohorts. We’ve got Parkinson’s Disease focus cohorts. And so although we’re called dementia platform UK by no means are these all dementia focused cohorts. Absolutely.

Speaker 12:

So overall, so this is a three day event. And is this the first time you’ve done this here in Exeter?

Speaker 13:

Yeah. So this is the first one of this year and we’re launching this program of five datathons in Exeter this year. We did hold one last year in October at the Turing Institute, which was almost like a pilot datathon, which was so successful we decided to hold five this year. And this is the first one of five.

Speaker 12:

So five this year. So work doesn’t stop at the end of the three days one would assume. You bring people together, they’re really focused, and then they forget about this and go back to their day jobs. What is it you actually hope to achieve through these?

Speaker 13:

Well, we’re really hoping that by attracting these young data scientists, and we’re really hoping that this pitch will go out to early career researchers specifically, that we’ll be able to break the back of these analyses and encourage them to take these through perhaps to publication level.

So we give them access, continuing on to perhaps three months after the datathon, we’re setting up user groups to keep this collaboration going and to nurture these through to output and outcomes. So by no means does this stop at the end of three months. So very much focused on let’s see what we can get out of the data.

Speaker 12:

That’s fantastic. So everybody else brings the ideas and you bring the data and the tools by which they can make use of it.

Speaker 13:

Yeah, absolutely. And then nurture it forward out of the datathon as well.

Speaker 14:

So I see a lot of patients in clinic and I mean, I think… So HD is really kind of characterised by three kind of pillars of symptoms. So there are the motor features. So you’re in the introduction, you mentioned that kind of hyperkinetic symptoms. So career and involuntary movements, people also get slowing unsteady gait in coordination. So it’s quite, actually a diverse movement disorder. The second pillar of the kind of HD symptomatology are the cognitive features. So this would be kind of what you may call the HD dementia and these largely fall into the kind of executive function bracket. So people with HD have difficulty kind of… They get a lot of cognitive rigidity, they have difficulty processing things or keeping up and changing their minds and can get overwhelmed quite quickly.

Sometimes they can be a bit impulsive in their decision making. It’s those kinds of executive functions that typically go wrong, especially early in the disease when the degeneration is relatively limited.

And then the third kind of pillar that I’ve been treating for the last couple of years in my clinic is the other neuropsychiatric features. So HD is associated with a lot of psychiatric disorder. So I see a lot of depression, anxiety, irritability, sometimes aggression. I rarely treat, well not uncommonly, treat psychosis. So quite a wide range of psychiatric features. And so the three together really kind of make up the clinical symptomatology of HD. And I think some of the things that are quite challenging about it are the interactions between those three things.

So when people have kind of fixed… That have cognitive impairment, that means that they’re quite rigid in their thinking. It’s then quite difficult if you’re trying to treat them for something like irritability or depression. So it’s a very devastating dementia, really. And, and certainly, I say this as a psychiatrist, but I certainly think HD has this huge prevalence of neuropsychiatric features and a lot of burden in terms of distress and disability comes from those features kind of above and beyond some of the other dementias where neuropsychiatry is certainly less prevalent early on.

Aoife Kiely:

So I thought I’d throw the floor open a little bit now and just ask everybody to tell us a bit about their experiences of actually gaining consent in dementia research and perhaps invite people to share some specific examples of what they’ve done.

New speaker:

So I’ve been taking consent for 15 years now. I worked for many years in a dementia unit in a hospital in Spain. And I remember these, yeah… I have this memory of this man who was a participant in one of our studies and I was still a uni op clinician. And this person asked to be re-consent every time that he came for the research visit, because he could not remember very well what has been going on in between visits? He asked if every single time that he came for a research visit, he could be explained everything in the project. And we could make sure that he still agreed with what he had signed. And I found it… because Noah has, this was completely new, I have never bumped into a situation like that before. But I saw how the Dean and the PI managed the situation.

So the doctor that was in charge of this study, he was very accommodating and he had a conversation with this person and of course we agreed that this was the way we were going to do it with him. And the whole thing worked together to make it easy for everyone. And that’s how we did it.

And that was a turning point for me because the termination of this man trying to retain his autonomy and also making this effort for explaining that his self determination was important and being brave enough to ask this, because this research environment in the hospital they can be intimidating and he did this. And also the reaction of the PI and the doctors that were so understanding and flexible and respectful that was a turning point for me because it added a different dimension to my understanding of the consent process. And I understood that it wasn’t only about a legal ethical requirement of bureaucracy. It could be a human relationship and it could be flexible. And you could be actually supporting people with cognitive difficulties to remain in power and to remain autonomous.

Anna Volkmer:

So when you’re talking about, then, language and communication like that, and within a research kind of field, how do you measure language and communication?

Jack:

I mean, it’s a complex question because there are two different questions embedded within that question. And one is, what should we look at? And as Rosemary said, there are many different levels from sounds words, sentences, appropriateness.

And as we’re looking at different types of dementia, different ways dementia can change your brain, we can imagine that any of these levels or a combination of these levels change. And also each of these levels itself is very complex. There’s many different aspects of grammar to look at, many different aspects of word processing, et cetera, et cetera. So the one question is what should we even look at? And there’s a bit of a variable hunt at the moment where different labs are trying to figure out which variables to look at to profile different types of dementia, pick up change early, track change over time.

And what we are looking at is… One thing that we bring into the mix that is, I think, rather new, at least in this field is the ability to produce rare language. So to say something that’s not very common, to produce a new word combination or rare word combination. Of course, it turns out that this is harder than saying something that you hear all the time. Okay. So what we hear all the time, sometimes called formulaic language, the word sequences are very fixed. They have a very specific meaning, for example, in com conversation, there are only so many ways I can say, you’re welcome and you’re welcome is the most common way. That’s a formula. And it turns out that as my language system becomes affected by dementia, the combination, my ability to come to form new sentences and phrases decreases.

So I’m more restricted to what’s common, and it should perhaps not be a huge surprise, I think. Because as we see in dementia, generally, that it becomes a challenge to be in a new situation to handle new information, turns out in language it’s just the same. It becomes difficult to do something new with your language system.

And then the other part of the question is: how should we look at it? And in a clinically meaningful sense. So we can’t have a human sit there and transcribe everything and hand analyse. Every sample takes way too much time. Thankfully, with the advance of machine learning, computer analysis, et cetera, we’re getting closer and closer to the point where you just speak into a microphone and get maybe meaningful signal out. That could mean that analysing language could be very, very cheap, right? Because if all you need is a bit of software on a computer and a microphone that is much cheaper than putting someone inside an MRI scanner, for example.

Speaker 9:

Well, I thought that the sleep talk was really interesting. I thought that the EEG data that she was using was cool, that she had stratified her study population by age, and was showing that older age groups had clearly different patterns, with her imaging and the analysis that she did. It seemed like a lot of association type analysis. I wasn’t sure about the clinical implications exactly. That might’ve been a little over my head or maybe has still yet to be fully fleshed out. But I think the associations seem to be there.

You know, what the mechanism is, is not clear to me. Whether it’s this sort of vascular dilatation and flushing of whatever solutes you might be carrying in your blood, or if there’s some other mechanism of risk that sleep is otherwise beneficial for.

I did get the sense that we’re all kind of in trouble. Because she was saying less than seven to eight hours is a risk.

Speaker 14:

That was really specific though because it was less than 7 to 8 hours was a risk, but anything over eight hours was also a risk. So you literally have to sleep for seven to eight hours.

Adam Smith:

It wasn’t just on dementia either, that was on health as a whole. That was on cardiovascular health.

Speaker 9:

But that’s reverse causation too because people that sleep a lot might be trying to deal with something. I saw that it seems like [crosstalk 00:28:53] other disorders. Exactly. You know, and I thought that was probably true of the pharmacological association she was sharing. She was saying some of these anti-psychotics, and I think that benzodiazepine was one of them. That she was showing that there was a risk from or an association, a negative association, but I thought that could be confounding by indication.

Voice Over:

This was a podcast brought to you by Dementia Researcher, everything you need in one place register today at dementiaresearcher.nihr.ac.uk.

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