Dr. Penny Moyle and RAD – Dementia Breakthroughs

Transcript

Ash de Neef: Penny thank you so much for joining us today on the podcast.

Penny Moyle: Thanks very much for having me.

Ash de Neef: Can we start with a little bit about your background and how you came to work with Race Against Dementia?

Penny Moyle: Sure. So my background is actually the business psychologist. That was, I guess my first career. I’ve worked in that area for nearly 20 years. And only latterly have come to working in a dementia charity that came about because the company I was working for was sold at the end of 2016. So I was looking for a new challenge and something meaningful to do.
And I was talking to a colleague who happened to be a headhunter and was also involved in the dementia world. And she said to me, “have you ever thought about working for a charity?” And i thought “that could be interesting”, and she introduced me to Sir Jackie and my life changed.

Ash de Neef: Fantastic. So you had no experience of working with a charity before Race Against Dementia?

Penny Moyle: No experience of working for charity, but experience of being a CEO and managing a medium sized business. We had about 200 employees. So the biggest change for me is that I went from managing about 150 to 200 employees to being myself and one other person.

Ash de Neef: Wow. That is a big change. Was there much of a difference between working for a for-profit company as opposed to working for a charity?

Penny Moyle: I think charities have different rules and regulations, so that was a whole new learning for me. There was also just learning about the dementia world, about the disease, about the science, about the sort of global statistics and all that kind of stuff. So that was new content.
But I think for me, the biggest thing was going from having, a marketing team to do marketing for me to going, “Oh, I do everything. That’s interesting.” I go from writing strategy meeting with trustees, meeting with potential donors – some of whom are quite famous people. To writing website content and making sure the bills are paid. So it’s got an enormous breadth to it, which is quite fun.

Ash de Neef: Absolutely. And now we’ll talk a bit more about Race Against Dementia in a moment.
But you mentioned that when you started working, you needed to skill up and learn a lot about dementia and the field and the state of things. What was that process like?

Penny Moyle: One of the great things was that this headhunter that I referenced has also written a book about dementia. She said when her mother was diagnosed with dementia she wished there’d been a book to give her that introduction. So after her mother sadly passed away, she wrote that book. So that was my initial introduction.
I also very quickly, once I started working for Race Against Dementia was able to hook into the network that Jackie had already created, because he’d already been on a bit of a dementia journey for the previous year or so.
So I was very quickly talking to professors around the world about their view of dementia and what they recommended I should learn about. So that was a huge leg up into the area. Also, there were connections in with other dementia charities, because actually connecting in with other dementia charities and working on a partnership model has been very big for us.
So we’ll shortly talk about Dementia Australia, but in my initial phase, it was Alzheimer’s Research UK. And meeting the people there gave me a grounding in everything I needed to know about dementia, but actually also about running a dementia charity. And we worked quite closely together with them.

Ash de Neef: Fantastic. And Race Against Dementia has somewhat of a reputation for being involved with cutting edge research. So you would have been involved with some of the most recent and exciting discoveries within dementia research?

Penny Moyle: Yeah. And I think Jackie’s sort of reason to start up Race Against Dementia is he just felt that all the effort that has been put in so far, clearly hasn’t given us any disease modifying treatments.
And that of course was a huge disappointment for the whole Stewart family. When lady Helen Stewart was diagnosed that there weren’t treatments that they could try out or do anything with. So Jackie really wanted to change that. And so that sort of led in to this idea of we need to do things differently.
We’re looking for greater level of innovation and what is it that we can do that might really make a difference. And particularly landed on the idea that we want to invest in early career researchers. We need to get new blood into this system. We also just need more researchers in the system. I don’t know if you’re aware that for every dementia researcher, there’s something like four or five cancer researchers.
So if we want to make the kind of progress that cancer has made in the last couple of decades, we need a lot more people to join this race.

Ash de Neef: What are some of the programs that Race Against Dementia is running to get the timing?

Penny Moyle: The main thing we run is the Race Against Dementia post-doctoral fellowship program.
We’re a small charity we’re fairly new, so the numbers are not going to sound all that exciting, but we need to punch above our weight. In our first round of funding, we appointed three post-doctoral fellows in collaboration with Alzheimer’s research UK. Then we fairly quickly appointed one at the Mayo clinic in Rochester, Minnesota.
So we have those four who’ve been in place for over a year now and they’re quite geographically dispersed. So we have one who’s currently in Florida who will be moving to UCL in London later this year. We have another, who is attached to the Mayo clinic in Minnesota, but it’s currently actually in Amsterdam.
She couldn’t travel over the last year when she’d expected to do that travel due to all the reasons we all are very familiar with. We have one in Scotland at the university of Edinburgh. We have one in Cambridge in the UK. So we’re already got a reasonable geographical coverage despite having only four in place.

Ash de Neef: That must be quite exciting to have this be a worldwide endeavour. Is that always been part of the goal with the fellowship program?

Penny Moyle: Yeah, definitely. When I first met Jackie, I said, what was important to him? And he was like speed and urgency youth, as he likes to call anybody under 50 and global was always part of the deal.
So one of the reasons we’re talking today is that we’re appointing two new fellows we’re announcing just this week – both of whom are in Australia.

Ash de Neef: Fantastic. And by the time this episode comes out, they will have been announced, but we’re very lucky to have them here with us on the podcast. Penny, would you like to introduce our guests today?

Penny Moyle: So I’m really excited to welcome Andrew McKinnon and Kunle Bademosi. Each of them post doctoral researchers, Andrew in Sydney Kunle in Queensland. But it’s probably better that they talk about their own research than me try to paraphrase.

Ash de Neef: Fantastic. Welcome to you, both Andrew and Kunle.

Dr. Kunle Bademosi: Thanks Ash.

Dr. Andrew McKinnon: Thanks, Ash. Appreciate you having us here.

Ash de Neef: Kunle, congratulations for receiving the fellowship. What does this grant mean for you?

Dr. Kunle Bademosi: Thanks Ash indeed first, I’ll say it comes with a lot of excitement and anticipation. I remember receiving the news for the grants late in December. And it was just a perfect way to end the year after the whole way 2020 went.
It was the highlight of 2020 for me, the day I got the news. And it gives me lots of opportunities. One is that I’m able to continue to do what I actually love doing, which is actually asking scientifically relevant questions, not just scientifically relevant but also questions that are relevant for the society.
And we know the impact dementia has on people around us, not just in terms of the numbers. But also in terms of the cost, the emotional costs. Financial costs, and in many ways I see myself as being well positioned by this post-doctoral fellowship from Race Against Dementia and partnership with Dementia Australia’s research foundation. This fellowship positions me to be in this place, be able to answer these major questions in the field of dementia. And it gives me the opportunity to work in this environment where I have the best people in the field of dementia here in Queensland, also collaborate with other people all around the world.
So it essentially builds my network and shows I’m able to help society and actually keep doing what I actually love doing. Which has always been a motto for me that I have to really enjoy what I’m doing and the questions I’m asking, there are things I am looking forward to, to asking and finding solutions to that.

Ash de Neef: Fantastic. And I had a brief look at the research that you’re proposing and it’s way above my knowledge. Can you give us a little overview of the questions that you’re going to be asking?

Dr. Kunle Bademosi: Okay. So specifically I’m looking at questions on dementia, but not just any type of dementia, but specifically the type called the frontotemporal dementia.
And this is the type which I think is the second most leading cause of dementia in people who are just under 65 who live with any type of dementia and a key features. That is actually in these people, you have a loss of specific parts of the brain. That’s the frontal part of the brain and the temporal parts of the brain – hence the name frontotemporal dementia.
In normal conditions they control your mood, your social behaviour, your personality, [and] language and speech generally. So when this part starts to get compromised and undergoes a deterioration we have a sudden onset of changing behaviour. Change in speech patterns change in mood.
And so my question comes into exactly what we have at the moment, as Penny mentioned earlier. At the moment [there is] no cure. There’s actually no treatment, no drug therapy at all for frontotemporal dementia. And the big question is why? And the answers simple – we don’t know what causes FTD.
But one thing we know is that there’s certain proteins in the body which when functioning properly keep the body in good health. But in FTD or in frontotemporal dementia, what happens is that these proteins start to clump up. So you can imagine, what should be one suddenly becomes like 100 all in one small space.
So this proteins essentially clump up. And that makes things very difficult for the brain because when they clump up, ultimately they become very toxic to the brain. And essentially that’s what leads to the brain parts and the frontal parts and temporal parts dying.
So here’s what my research is about. My research involves actually looking at those proteins.
Now these proteins ,we’ve known for a while that they clump but we’ve never seen them before. So I make use of what we call advanced imaging tools and. That is imaging tools that have almost about 10 million times the magnification of a standard digital camera. So it means I can actually zoom in very great details to see these proteins.
And all I want to ask is simple. What happens to this proteins before the clump? What happens while they’re clumping and what happens after they clump? And that’s just one of the key parts of my research question.

Ash de Neef: Yeah. Amazing. So it sounds if you can get some sort of understanding of where they come from, what they’re doing, where they’re going, maybe you can understand one of the causes that’s leading to FTD.

Dr. Kunle Bademosi: Exactly.

Ash de Neef: Wow. And then perhaps if we’re lucky leading to a treatment, if we can understand how to deal with these protein clumps.

Dr. Kunle Bademosi: Yes. And that’s the second part of my research where so the body actually has a way to deal with these things. Naturally it has something which is like a waste disposal machinery that either recycles or actually just destroys the clumps.
But in FTD this machinery is compromised. So the second part which perfectly leads onto, thinking of therapeutic strategies will be for me to look at this machinery that is compromised. And see what drugs actually could help this machinery to keep on working in recycling or degrading this protein clumps, which should not be in the body.

Ash de Neef: Great. And now circling back to what Penny said before about trying to bring people into the field of dementia research. Is your background in dementia research or are you just newly in the field?

Dr. Kunle Bademosi: I’d say not brand new, but I’m still like about three years into the field of dementia. So my research, my doctorate was all about understanding how general anaesthetics work and I was using this advanced imaging tools and I was able to get this very nice answers to how drugs like Propofol and Etomidate and Isoflurane work during surgery.
And that’s led me onto move to Belgium, where I was introduced to the field of Parkinson’s disease. And that was my introduction to dementia field. And as we know, Parkinson’s disease is the second leading cause of dementia after Alzheimer’s.
And so then I started to understand the premotor symptoms that occur in Parkinson’s 20 or 30 years before people have symptoms such as sleep fragmentation loss of smell way before any motor symptoms. And my investigation was focused on that. And essentially what I’m doing now in FTD research is I’m taking my skill from my PhD, where i’ve looked at this advanced imaging tool as well as my experience with dementia and Parkinson’s disease.
I was led to answer a question on frontotemporal dementia.

Ash de Neef: That’s great. And Penny, that must be a really nice example of being able to take skilled individuals who have a know-how and experience in a different field and then bring them into dementia research.

Penny Moyle: Absolutely. And I think, not only does that help with the numbers game of just bringing more people into the dementia research space, but it’s that thing of thinking differently, bringing people who’ve been thinking about something else and how do they apply that to the problem of dementia. Yeah. Perfect example.

Ash de Neef: Yeah, Andrew congratulations as well. You’ve also received this post-doctorate fellowship.

Dr. Andrew McKinnon: Yeah, thank you. It’s been an absolute pleasure. I’m really grateful and very excited to join the team. Sir Jackie’s sort of vision to apply high-performance elements to dementia research I find is a particularly intriguing approach, which may hopefully ultimately streamline dementia research and allow the breakthroughs we’ve made at a more rapid pace.
What I particularly like about this fellowship – and long, long time ago in another life I did a business degree. So come from a business background in marketing management, and further on and went on to psychology and cognitive neuroscience. But I can see the parallels and I can see that there’s great potential there for the two to be combined.
And I think that we’re very fortunate in receiving these fellowships, that we’re going to be able to engage with minds, not just in academia, but across industry, external stakeholders, policymakers, and so on. Because i think this is going to be very helpful, not just in disseminating the importance, but also allowing for integration of expert knowledge across the diverse number of fields to move dementia research forward.

Ash de Neef: Maybe it’s a case of whilst there are other post-doctorate fellowships out there, this is somewhat smart money. Because it’s connecting you to really high powered people in this field of research. And so Jackie’s personal, his motivation to really tackle this problem head on.
Now the research your undertaking I think is to do with sleep and the connection with the onset and progression of dementia. Is that correct?

Dr. Andrew McKinnon: That’s correct yes.

Ash de Neef: Yeah. Can you give us a bit of an overview? That’s a bit more detailed than my summary.

Dr. Andrew McKinnon: What we know so far is that sleep plays a vital role in the maintenance of key brain processes.
So pretty recent research in the last couple of years have identified the lymphatic system, which seems to clear amyloid beta, one of the pathogenic biomarkers related to Alzheimer’s disease during sleep. And the sleep wake cycle regulates this clearance of the brains lymphatic system, so it happens much more during sleep than when you’re awake.
This accumulation also goes far prior to manifestation of any sort of cognitive decline that you can detect on testing. And I’m also an endorsed clinical neuropsychologist. So I’m at both ends of this, and I’m very much interested in the translational aspects of how you can bring cognitive neuroscience through, into the clinic in meaningful ways.
We talk about sleep disturbances or talking about things like sleep quality, sleep fragmentation, misalignment of sleep period timing. So basically circadian rhythm changes. So alterations in melatonin secretion, which tend to be associated with one and a half times higher risk for developing Alzheimer’s disease and also sleep wake disturbances themselves are known to impair the formation of new neurones in the brain, which in areas that are very important for memory consolidation.
And so this is key bi-directional relationship between sleep disturbances and neuro-degeneration, and that’s where I come into it. So the vast majority of dementia cases are either Alzheimer’s or Alzheimer’s with vascular dementia pathology. And they often go hand in hand around about a third of dementia cases are believed to be preventable due to modifiable risk factors that start accumulating from mid-age.
So things like hypertension, episodes of depression, lifestyle factors like smoking, excess alcohol intake, et cetera. And we believe that sleep also has the potential to be a a target as a modifiable risk factor. It’s just that thus far, a lot of the studies being cross sectional -so one time point. And we haven’t had the longitudinal data to make a strong case yet for sleep to be added to the list of known modifiable risk factors.
But it’s certainly linked to dementia onset. During my PhD, I did a lot of work on those with what we call mild cognitive impairment, which is an at-risk stage between normal, healthy, cognitive ageing and dementia. Where about 45% of people will convert to dementia within five years. And we looked at those with MCI and sleep disturbances, versus those with MCI and no sleep disturbances and found reduced connectivity in brain networks, in areas that are specific to things like memory consolidation.
So it seems quite apparent that sleep has an important role to play. And the main aim of my research for this particular fellowship is to look into that further and provide a stronger evidence base for it to become officially recognised as a modifiable risk factor for dementia.

Ash de Neef: Fantastic. So you mentioned the longitudinal study there. Is that something you’re able to undertake this fellowship?

Dr. Andrew McKinnon: Yeah. So effectively what we’re doing is in an older adult cohort that are at risk for, or in the early stages of dementia, we’re going to be measuring them at two time points.
So year one and year three, and we’re going to use actigraphy. So wrist-worn actigraphy and also finger-worn oximetry and that sort of measures things. Like oxygen desaturation, which is often seen in a very common sleep disorder, obstructive sleep apnoea. And so the constant sort of starting and stopping and breathing throughout the night, disrupts the flow of oxygenated blood to the brain increases the risk for dementia.
And then, because I am very interested in the translational element. The second part of it is to develop and validate tools using machine learning from all the data that we collect from the first time to produce weighted risk composites can produce clinical reports. individualised clinical reports, I should say for clinicians use in clinic that can say, “given that you are at this level on these particular variables, this confers 20% risk for cognitive decline over the next three years.”
And then they can go about addressing whether it’s extreme hypertension or getting involved in exercise programs, whatever, because as stated before, there are no curative treatments for dementia.
So the earlier we can detect these changes in cognition, the earlier we can start intervening and hopefully have a preventative approach.
Ash de Neef: Fantastic. So maybe in a few years time, If the research proceeds in a successful way, we might find wearables paired with this sort of data to provide modelling and monitoring for an advanced screening. Is that right?

Dr. Andrew McKinnon: That’s one possible outcome. Absolutely.

Ash de Neef: Yeah. Fantastic. Penny, this is also another great example of a piece of research that can really really change the way that dementia is viewed and is treated.

Penny Moyle: Yeah, and I love the idea that it gives us something positive that all of us can be doing thinking about prevention and, or at least reducing our risk factors.
Sleep is something that we all need. And this is just another reason why it’s so important and we should be paying attention to our own sleep patterns. And it could add into the other modifiable risk factors that we already know about which I usually summarise as anything that’s good for your heart is good for your brain. And we tend to know what’s good for our hearts. Eat well, exercise, all of those kinds of things. It sounds a bit dull, but I think the benefits are so worthwhile.

Ash de Neef: Yeah. I’d rather be dull and healthy.

Penny Moyle: We are living longer. But the dream was never, that we lived a long time and spent our final years with dementia. The dream is to live long and healthy.

Dr. Andrew McKinnon: And I think an important thing to note, sorry to jump in. I just forgot to mention that a lot of these risk factors start to accumulate from approximately midlife. So the earlier you get onto them, the greater, the chance of prevention later on.

Ash de Neef: Yeah. This is where that longitudinal study is really coming into play here. And we can start getting data earlier and earlier.
Anyone feel free to jump in on this question, but this was possible also through Dementia Australia’s partnership with Race Against Dementia. What was the application process like?
Kunle or Andrew, if you want to lead here.

Dr. Kunle Bademosi: Okay. Maybe I’ll start.
As I mentioned, I was, I got some experience working in Parkinson’s disease in Belgium, and I moved back to Australia right in the middle of COVID. I arrived in Australia on the 31st of July to start to a one year contract or less about nine months contract. And I remember talking with my current boss Adam Walker about potential fellowships to apply for.
And he was like, “Oh, there’s actually a fellowship to apply for, which is due in three weeks time”. So I was right in the middle of my hotel where I was reading up on frontotemporal dementia while I was in the quarantine. And I knew a lot about it, but then to come up with a project to come up with research questions, my aims, my milestones, and essentially write it all, get feedback. And actually go through the whole submission process…It was pretty surprising I could get this done, in the short while of about three weeks. Which for me was a great experience because I had previously had experience writing – applying for a fellowship and writing within a short time interval as well.
So that was great. I think I especially loved the interview component where after we were selected a couple of us had to be interviewed. I really enjoyed that because it gave me the opportunity to interact, not just in the context of trying to defend my research questions, but also just to, put it out there and get the feeling from others as to how excited other people could be about what I’m also excited about. So the whole process from writing to actually getting a positive response was very great for me.

Ash de Neef: Penny. Can you jump in here and give us an idea of what you were looking for in these interviews?

Penny Moyle: So I think we look at essentially three things we’re looking for. The right person.
So we’re looking for people who have demonstrated that they are brilliant at science. We’re looking for them to have an exciting and innovative project. That was what Kunle was busy working on while in quarantine. I loved that he made great use of that period of isolation and then we’re wanting to make sure they’re in the right place, that they’re in an institution that can support the particular projects that they’re working on.
So that’s what happens in the written review process – and I’m not sure if we said but we had over 40 applications for these two positions. So there was quite a lot of work that went into the pre-interview stage of working out who met the criteria of those sort of three areas. And then in the interview, we are looking for that kind of spark of something different and engagement in this idea of connection with Formula One.
So we haven’t talked much yet about that connection, but each of the research fellows in our program get connected with Formula One, at least at a high level, but they also have a mentor. Who are either in formula one or some other kind of high tech commercial enterprise, just to give some sense of ways of doing things differently and particularly ways of doing things more quickly and in a more streamlined way.
So that was something we could talk about a bit in interview and gauge to make sure really that. Any prospective fellow knew what they were signing up to. What they will get is the grant -and it’s nice to get some money to have the research done, but they also need to engage in this idea of being part of a developmental program. Connecting with the other fellows in other parts of the world and particularly connecting with F1 and what that might be able to bring into their research and approach.

Ash de Neef: Yeah. Can you share some of the some of the impacts that have been made by these connections with F1 with previous fellows?

Penny Moyle: Yeah. So working with McLaren without going into too much detail, so McLaren, all the formula one teams do this, they all have lots of sensors on the car and indeed on the driver in the car.
So they have a lot of sort of tech around that and indeed that how to analyse the massive amounts of data that come in from you having lots of sensors on an object or a person. So there are a couple of different applications coming out of that potentially for us. One is potentially using that sensor technology with people with dementia to be able to track them day to day and what they’re doing and what their activity levels are. And then analysing that, because then you can get a much better sense as a clinician of what’s going on with that person than you get, when you just meet them periodically one-on-one.
So that’s an interesting application, then there’s all that machine learning, artificial intelligence stuff, which can be applied to just about anything. And we heard Andrew earlier mentioned that machine learning might be part of his work. So it might be that connection with Formula One will give him access to different techniques than you might not otherwise have access to.So this idea of the cross-fertilisation there. So those were a couple of examples we’ve got in the aether already.
Then the other area is actually partly how we’re doing this part of our vision, which is to inject formula one attitude into dementia research.
So when we started looking at that early on with our first cohort of fellows, we were aided by a professor from Cranfield university, Mark Jenkins.
Who’s made a study of what makes for successful Formula one teams? Because we know that sometimes the same team can be successful one year and less successful the next and they each have their eras of pride and success. And he’s made a study of that. And also how that information can then be applied for other organisations to help them be successful.
And as you might imagine, things like collaboration, communication, and teamwork and leadership all come up time and time again. So part of what we’re putting together for the Race Against Dementia fellows is a development program based on things that are done as best practice in formula one. And what this ends up looking like is not dissimilar to what I would have called a high potential program in some of the larger organizations I’ve worked in as a business psychologist.
So how you take people who are relatively early in their career and you up-skill them in things around personality based self-awareness. How that then impacts on how your communication style, you have your preferred style, but other people have what they want to hear and how you’d flex your communication to influence people of the different audiences and stakeholders that you might need to work with.
So that kind of thing. So we have this development program, which shows very familiar territory to me, from my background, for our Race Against Dementia fellows. And we’re implementing that in a way that again is inspired by Formula One. Formula One is very famous for these quick learning cycles where they’re racing every couple of weeks and sometimes even more quickly than that in the sort of current regime.
And they make changes to the cars between each race. So they have a very rapid learning cycle of “we tried this, this is how it works. This is what we’re going to change. This is what we’re going to do next time.” And so within our own development program, we’re doing that too.
So we’ve tried out some stuff in the last year with our first cohort that is continuing on, but based on their feedback, Andrew and Kunle will experience some slightly different things hopefully slightly better. And then next year, when we appoint our next group of fellows, again, they will experience some slightly different things based on what we’ve learned so far. So this sort of constant learning piece at a couple of different levels feels really exciting to me.

Ash de Neef: Absolutely. Penny, Andrew, and Kunle thank you so much for your time today and good luck with the research and the future.

Dr. Andrew McKinnon: Thank you very much.

Penny Moyle: It’s been a pleasure.

Dr. Kunle Bademosi: Thank you