Podcast – AAIC 2019 Day Two

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 again, I’m Adam Smith. And today I’m hosting this special podcast recording from day two of the Alzheimer’s Association International Conference currently taking place in Los Angeles. And for those who didn’t already listen to yesterday’s, which is day one, today’s day two, honestly, it’s conferences, you lose track of days. Today’s day two, and you’ll be listening to this when we’re at day three.

Adam Smith:

So if you didn’t listen yesterday, we’re recording every day from the conference, sharing news and the highlights from the conference, particularly with everybody who couldn’t manage to make it today. And today, I’m joined by… Do you know what? I’m going to attempt it. I’m going to have a go, Riona…

Dr Riona McArdle:

Close.

Adam Smith:

McArdle from Newcastle University. Some of you will remember Ri from last year. I’m also joined by first timers, Dr. Astrid Suchy-Dicey-

Dr Astrid Suchy-Dicey:

You got it.

Adam Smith:

From Washington State University. And Dr. Sara Imarisio from Alzheimer’s Research UK, and you’re the research manager there. Anyway, we’ll do that next.

Adam Smith:

So, hello, everybody. Thank you very much for joining us today. Can we start with a little round-table, so you can introduce yourselves and maybe introduce yourselves, tell us a little bit about your work? So Ri, you can go first.

Dr Riona McArdle:

Yeah, hi, as Adam said, my name is Riona McArdle. I’m a research associate in the Brain and Movement Research Group in Newcastle University. And my key research interests are looking at gait analysis and the use of wearable technology for both the differential diagnosis support of different dementia sub types, especially Lewy body dementias, and also just understanding how dementia can impact a person’s daily living.

Adam Smith:

Fantastic. Thanks, Ri. And Astrid?

Dr Astrid Suchy-Dicey:

Hi, yes. I’m Astrid Suchy-Dicey, as Adam said, and I’m a neuro epidemiologist with Washington State University’s new Elson S. Floyd College of Medicine, which is located in Spokane, but I’m actually located in Seattle. I study neurodegenerative disease and vascular brain injury in American Indian populations.

Adam Smith:

Fantastic. And our token American. We’ve been keen to have more people from outside of the UK join us. Thank you very much.

Dr Astrid Suchy-Dicey:

Yes. I’m an American.

Adam Smith:

And we should, we did just grab you off the conference floor one day, yesterday, to persuade into doing it. So thank you ever so much though Astrid, for joining us. And Sara?

Dr Sara Imarisio:

So my name is Sara Imarisio, and I am the Head of Strategic Initiative in Alzheimer’s Research UK. My role in the charity is to overlook strategic initiatives that include the UK Dementia Research Institute, as well as the Drug Discovery Alliance. And then I’m in charge of running the annual scientific conference of Alzheimer’s Research UK.

Dr Sara Imarisio:

Plus, I am responsible of the researcher engagement, and this is why I am here at the AAIC.

Adam Smith:

Engaging with the researchers.

Dr Sara Imarisio:

Yes.

Adam Smith:

Does that include persuading them that the UK is a great place to work, and encouraging all those ECRs from the US and elsewhere to come to the UK?

Dr Sara Imarisio:

Correct. What I found, it was very interesting at this conference, at the moment it was pointed out by Maria Carrillo was that she was saying that actually every session is a mix of senior and early career researcher presenting. In such a big conference, I think it’s very important to give voice to the new generation. And yesterday, she was mentioning that actually they have increased four times the Dementia Research Fund for a project to support basic research.

Dr Sara Imarisio:

I found that was amazing, because obviously, UK is quite behind in that case. And while we are good in thinking it is important to increase capacity, for me now, the problem is making sure that we increase capacity, but we retain the capacity that we have created. And so as a charity, we are investing a lot of effort in making sure that the government is buying in, in the importance of funding more with this 1% campaign, where we would like to support more dementia research.

Dr Sara Imarisio:

I think that this conference, it’s a huge platform that is showing that we are on the right track in UK. So it would be fantastic to have more US scientists either applying to UK funding or actually moving to UK or creating collaboration with UK scientist.

Adam Smith:

We have to get a plug in now for Alzheimer’s Research UK, do have funding opportunities. Are yours open right now, your calls, or have they just closed, the recent round?

Dr Sara Imarisio:

They just closed and they’re going to be open soon. I think at the end of July.

Adam Smith:

And we list all those on our website as well at dementiaresearcher.nihr.ac.co.uk.

Dr Sara Imarisio:

[crosstalk 00:05:04].

Adam Smith:

So just come to our website first, and you can get all the information on funding from there and from Alzheimer’s Society as well and from the NIHR and other places. For anybody that’s listening overseas, which we know that, I don’t know, more than 50% of our listeners aren’t in the UK. So that’s always good.

Adam Smith:

So what are we going to talk about first? Should we start, what about last night’s welcome reception, which was fantastic, right? There must have been so much working going into organising that. For those who didn’t know, it was at Universal Studios.

Dr Sara Imarisio:

4,000 people?

Adam Smith:

4,000 attended in the end. Wow. And they all had to get coached from their hotels to the place, which explains the queues were long, right? They were big queues.

Dr Astrid Suchy-Dicey:

I heard that they were over 100 minutes long, near closing.

Adam Smith:

Wait. What do you mean you heard, you didn’t go?

Dr Astrid Suchy-Dicey:

I didn’t, but I got reports.

Dr Riona McArdle:

You didn’t go.

Adam Smith:

There was free food and drinks and Harry Potter rides.

Dr Astrid Suchy-Dicey:

I have a lot of friends in LA and I am trying to squeeze in seeing them as well. So I chose to go have dinner with them. But it sounds like I missed out on a good time.

Dr Riona McArdle:

I would choose Harry Potter over my friends.

Dr Astrid Suchy-Dicey:

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

Adam Smith:

You did all the rides, Ri? I know you did all the-

Dr Riona McArdle:

I did the Harry Potter rides. I didn’t do many of the others, because we queued for quite a while to get into the Harry Potter rides, but I got to do the virtual reality, which you did on the broomstick. And that was amazing.

Dr Sara Imarisio:

Really?

Dr Riona McArdle:

Yeah, I felt like I was actually on a broomstick. I was very creeped out by it, but incredibly in love with it at the same time.

Adam Smith:

I’m a big fan of those VR games, over real rollercoasters. I know they make you feel the same way, but I’m not a big fan of big rides.

Dr Riona McArdle:

I love roller coasters, but I did actually prefer it to the Hippogriff rides that they had because it was a bit more scary, I think, than the Hippogriff one. The only thing that was scary about the Hippogriff one was the barriers popping off on me right before I started, and they were like, oh, if that happens, just hold it down. And then it just started and I was like, oh, my God, I’m going to fall out this and die. But it was fun.

Adam Smith:

Well, I think we all had a lot of fun last night, and really well done to the Alzheimer’s Association for organising that. It really must have been a bit of an epic undertaking, just to organise that, let alone this huge conference, which I gather has got more than 5,000 people attending this year.

Adam Smith:

And once again, more than 50% of the people here are female researchers, which is fantastic. A tweet earlier saying that’s great, we just need to retain more because I think you can’t help but notice that the older people here are all men and the younger people are mostly women. So, we need to make sure that you’re still coming to this conference in 10 years’ time, which is the challenge. But I think that’s more to do with career structures and how they need to be organised to enable that, particularly in universities.

Adam Smith:

So shall we start then by talking about your own presentations? I guess Sara you haven’t presented while you’ve been here, but Astrid, you have?

Dr Astrid Suchy-Dicey:

No, I’m actually here just to soak up talks.

Adam Smith:

You’ve not been presenting.

Dr Astrid Suchy-Dicey:

I haven’t presented.

Adam Smith:

Ri, I know you’ve been presenting.

Dr Riona McArdle:

I feel like that has all led to me.

Adam Smith:

I should have paid more attention to my notes.

Dr Astrid Suchy-Dicey:

She’s making up for the rest of us.

Dr Riona McArdle:

Yeah, I presented. I had an oral presentation at the technology pre-conference, which is one of my favourite parts of AAIC, and it’s probably one of the most helpful parts to me. I’ve had a poster yesterday and today as well in my PhD research.

Adam Smith:

So what were your posters today about?

Dr Riona McArdle:

My poster today was looking at the use of wearable technology to differentiate different dementia sub-types and also, about where we assess gait with the technology. So if you assess it in the clinic, what does that tell you in comparison to if you assess it in a person’s own home and community environment?

Dr Riona McArdle:

And it just addressed some of the challenges that we still have to face, with the use of wearable technology, in order to translate that research back into a clinical environment.

Adam Smith:

Do you use gait in your work, Astrid?

Dr Astrid Suchy-Dicey:

I would like to actually. We’re struggling a little bit with figuring out how to diagnose cognitive impairment in Alzheimer’s in vascular dementias in American Indians and other undeserved racial ethnic minorities. Particularly because a lot of the validated cognitive assessments are not necessarily validated for other cultural and linguistic groups.

Dr Astrid Suchy-Dicey:

And so we’re looking for cultural neutral measures. I think gait is a really exciting one. Wearables seem pretty promising. Obviously, it’s not necessarily… I can’t think of a way that culture would really influence gait. But maybe you can tell me.

Adam Smith:

Maybe be back to the types of professions that people have done as, the kind of jobs that they’ve done, whether they be manual workers or office workers. Does that make a difference to gait?

Dr Riona McArdle:

I’m not sure if the research on that… I think there is differences between, for example, men and women. And I know that there is differences between countries and the things that would be accepted as a normal gait speed. So in some countries that could be slower than in other countries. And so things kind of have to be stratified towards that.

Dr Riona McArdle:

And you have to understand that when you’re doing it, at the moment, we’re still really in the stages where we’re taking big groups and just trying to find out, did they look different from each other, rather than that individual level, which I think we talked about yesterday in the plenary session as well, they talked similarly about other kind of biomarkers and how that’s still at a group level rather than an individual level. And so it’s worked for everyone.

Dr Riona McArdle:

But I would say that one of the good things with gait, in using it as a complementary supportive marker for diagnosis is that it is that kind of thing, it’s not dependent on language, it is just a person walking. And as long as they have the ability to still walk, then it’s useful.

Dr Astrid Suchy-Dicey:

Of course. That’s the limitation.

Adam Smith:

Does that focus then at the moment on differentiating diagnosis, assuming that they’ve got a diagnosis in the first place, rather than being a point to say, you must have cognitive impairment because of your gait?

Dr Riona McArdle:

So there’s two different tracks of this going on at the moment. The work that I did followed on from a large body of work that looked at longitudinal progression studies, monitoring things like gait speed, and seeing that as it slowed down, how that correlated to people going on to develop diagnosis of dementia. And basically it found that it could be predictive of dementia up to 12 years beforehand.

Dr Riona McArdle:

What I did with my own study was I took people who had established cognitive impairment due to different disease sub-types. Because you need to get it in the established impairment groups, in order to find the signature of gait impairment, that’s specific to those groups, and then work backwards to try to find out, can we also get that in people before they have developed dementia? Are we seeing a pattern that’s Lewy body dementia coming eight years before Lewy body dementia is diagnoseable?

Dr Riona McArdle:

And so it’s still really in the early stages, but it’s certainly getting promising results from my own PhD. So hopefully, it will begin to pick up a bit of traction now.

Dr Sara Imarisio:

I have a question. Can I ask?

Adam Smith:

Yeah, of course, please do so.

Dr Sara Imarisio:

I wanted to ask you, is your study part of a more combinatorial study? So looking at the gait, you’re going to sum this result to other results that look for, in this code that you were studying. So were you looking at the level of cholesterol or the alkalinity code, the social activities, the lifestyle of a person? So that then you have gait plus-

Dr Riona McArdle:

Plus other things. So what we did, the key aim of my study was to find out if there was differences in gait impairment. So it was completely set up to look at that. And we looked at a large battery of cognitive testing within that as well, because we wanted to understand the relationship between cognition and gait.

Dr Riona McArdle:

With the wearable technology, we could also look at the gait in the home, but we could look at the habitual activities in the home, which could give us a little bit of information about some lifestyle factors. For example, how much a person is actually moving during the day, and also the pattern of what that looks like. Are they changing their walking behaviours throughout the day? Are they mainly taking short bursts of walking rather than long bursts of walking?

Dr Riona McArdle:

And I’ve had a bit of a look at that as well to try to understand what factors might be contributing to that. It wasn’t a study really set up to look at lifestyle factors though, and I would be very interested in understanding that further.

Dr Riona McArdle:

Particularly, I think about how people’s support systems and their own home environments are perhaps affecting and certain aspects of either how they deal with the disease or how the disease is progressing for them and how that might be impacting on their gait and habitual activity.

Dr Sara Imarisio:

That’s very interesting. And how people receive your talk? Did you notice that a lot of people were interested about the technology, gave a lot of value to the technology?

Dr Riona McArdle:

Yeah, I would say I think that I got good interest for it. To be honest, I’ve been at a few conferences recently, and I’ve had a few talks at them. And the research is certainly getting a lot more interest this year than I noticed it previously getting. And that’s coming at a good time because I’ve got good results that have now come out from the PhD that will be getting published soon.

Dr Riona McArdle:

I think people are beginning to listen to it. And we just have to try to make it better. Basically, get the research to a better level and get the technology ready for clinical use, and see if we can actually get clinicians to take this into their clinics and try to use it as a differential support.

Adam Smith:

I think people seem more comfortable as well with the idea of using wearable technologies to collect that kind of anonymized health data more so than… I’ve just seen a talk earlier where they were talking about the ethics around capturing data through these more subtle devices, like people talking to their phones and recording people on cameras and things like that when they might not be there.

Adam Smith:

Because it’s something that you’re wearing. It’s a constant reminder, although of course, if you were doing this over the long term, you can understand reassessing consent as you move your way through has to be considered. Although they remove their consent, we were talking about this last night, weren’t we? They could remove their consent by taking it off.

Dr Sara Imarisio:

But this is the advantage of the wearable technology, because if you don’t want to do it anymore, you just remove it.

Adam Smith:

Because the real interesting thing I think is going about this another way, which is people of our age, as I look around the room, not all my age, I’m old. Exactly. Two of us at least are wearing smart watches. What’s really going to be interesting is the data that we’re contributing now, actually in a few years’ time.

Dr Sara Imarisio:

I agree.

Dr Astrid Suchy-Dicey:

It’s a massive amount of data too. I don’t even know what to do with all of it. I just look at my watch and it’s overwhelming.

Adam Smith:

And we’ve seen that. I know I’ve talked about for a long time about using things like loyalty card data from supermarkets and things like that, to see what you buy and shopping habits and how that could have had an effect.

Adam Smith:

So fantastic. That’s really interesting. Thank you. Thanks very much, Ri.

Dr Sara Imarisio:

Congratulations.

Dr Riona McArdle:

Thank you.

Adam Smith:

And well done. Yeah, two posters and a talk.

Dr Astrid Suchy-Dicey:

Yeah, good job making up for the rest of us.

Adam Smith:

Justifying the funding there as well.

Adam Smith:

Okay, so let’s move on to the big topics of the day. So thinking about the big topics today, I’ve made a few notes here. So sleep has been the main topic today. And the potential for sleep disorders to be a risk factor, making a case for why that should be the case.

Adam Smith:

I think they also played up the blood biomarker presentation was a big talk of the day, but having attended it, there wasn’t any new data there, was it? It was bringing up to speed on what we might have already just read in the Al’s forum only… what was that? About six, eight weeks ago that that was out there.

Adam Smith:

Stress granules are being talked about now, but I feel really bad, we might have to talk about stress granules tomorrow when Robin is joining us tomorrow from Alzheimer’s Research UK. Because I know he’s attending that talk and that’s happening while we’re actually recording. So we probably can’t talk.

Adam Smith:

But I think we’re all fascinated to know what stress granules are. Did anybody, had heard that term before you came to the conference?

Dr Astrid Suchy-Dicey:

No.

Adam Smith:

No. I noticed as well the themes on the posters, there were, white matter neuro inflammation was all in these topics that have been highly talked about in years gone by, but I don’t know. I haven’t managed to make any talks on those today.

Adam Smith:

So let’s talk about the sleep one first. There is another thing to mention, that you talked about Maria Carrillo, a little talk earlier. She also mentioned that there’s going to be a satellite symposium in Greece in 2020, which is quite interesting, in their work to try and spread out and engage other countries in this. And a special global tau 2020 conference, that sounds exciting, doesn’t it? Global Tau 2020 conference in Washington in February.

Adam Smith:

I’m sure if you go to the Alzheimer’s Association’s website, they’ll be more information now to get involved in those there. They’re recommending people book early for the tau conference because there won’t be many places, it’ll be quite small as their first time, but they are planning to repeat it.

Adam Smith:

Okay, so the sleep talk was Ruth Benca from University of California. And essentially, she’d been looking at the risk factors and felt that sleep should be included amongst those. What did you think, Astrid, what did you think of the sleep?

Dr Astrid Suchy-Dicey:

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. And it seemed like a lot of association type analysis. I wasn’t sure about the clinical implications exactly. That might have been a little over my head or maybe has still yet to be fully fleshed out. But I think the associations seemed to be there.

Dr Astrid Suchy-Dicey:

What the mechanism is, is not clear to me, whether it’s the vascular dilatation and flushing of whatever cell 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 in trouble if it’s like… because she was saying less than seven to eight hours is a risk.

Dr Riona McArdle:

That was really specific though, because it was less than seven to eight 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:

And then that wasn’t just on dementia, that was on health as a whole, that was also on cardiovascular.

Dr Riona McArdle:

I don’t think I ever get seven-

Dr Astrid Suchy-Dicey:

But that’s like the reverse causation too, because people that sleep a lot might be trying to deal with something.

Dr Riona McArdle:

It is associated with other disorders.

Dr Astrid Suchy-Dicey:

Exactly. 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.

Dr Astrid Suchy-Dicey:

But I thought that could be confounding my indication, that there couldn’t be-

Adam Smith:

Coming back to basics, I thought what was interesting, we know that older people get less sleep and as you gradually got older, you do sleep less and there were lots of causes for that, weren’t they? In my notes here around things like… but there’s also a few… insomnia been one, but there’s about three posters as well in insomnia.

Adam Smith:

There’s a poster from somebody in South Korea, looking at relationships between insomnia and dementia as well.

Dr Astrid Suchy-Dicey:

Sleep apnea.

Adam Smith:

Sleep apnea and also as well the speed of progression, because they measured that in a nursing home and how much time… I would imagine actually by the time you get to nursing home, lots of people were sleeping for a long time because-

Dr Riona McArdle:

I suppose it depends then on the quality of their sleep in the nursing home, if they’re having short naps. They’re not getting into an actual deep quality.

Dr Astrid Suchy-Dicey:

But that can be a symptom too. That’s not necessarily a cause or a risk, it can also be a sequela.

Adam Smith:

There was a point that not only do we get less sleep as we get older, we also get less REM sleep. And taking longer to fall asleep, having more naps, waking up more often are all contributing factors.

Adam Smith:

But you made a good point when we were talking about this before Sara about, and I’m glad it wasn’t just me because what I couldn’t understand was whether what she was seeing was a cause-

Dr Sara Imarisio:

A consequence.

Adam Smith:

A consequence of dementia or a cause.

Dr Sara Imarisio:

Yeah, I really liked the way she presented your story around sleep and I think it was quite robust. I really liked the methodology that she was using, the way she was stratifying, but at the end of it, I didn’t really buy that it is a risk factor. I thought it is still unknown whether… it’s linked obviously. She proved it is obviously linked and there are many similarity apnea disorders with dementia and et cetera.

Dr Sara Imarisio:

But she didn’t really focus on, it’s a cause or a consequence of the disease.

Adam Smith:

This is slightly over my head, but is that whether these frontal fast spindles come into play? Because there are age related loss of frontal fast spindles and people with AD have the same issue, but they also have increased loss of internal spindles.

Dr Astrid Suchy-Dicey:

Posterior [crosstalk 00:23:28].

Dr Sara Imarisio:

Posterior, no?

Adam Smith:

And so whether that makes any difference. I don’t know, it was really interesting. What were the takeaways in the end? My notes here say that she seemed to suggest the sleep has a relationship between those that develop dementia and sleep problems.

Dr Sara Imarisio:

But we know also because if we look at the circadian rhythm, I think that the old pattern of sleeping in the circadian rhythm is disturbing people with dementia and the consequence is not so linked.

Dr Riona McArdle:

She said that they become more like night owls as they continue into the dementia phases in Alzheimer’s disease. It’ll be interesting to see what that looks like in other types of dementias as well, and see if it maps on or if it looks different. And if that’s showing some kind of different behaviour as well.

Adam Smith:

She talked about the circadian rhythms as well, clock rather, and that was obviously an issue, but she didn’t go into detail.

Dr Sara Imarisio:

Actually, it would be nice to see whether if you can start looking at people, if at some point, we will be able to look at early sign of dementia, whether at that point you can make a correlation between the two. So was your lack of sleep or your difficulties of sleeping a first sign of dementia?

Dr Riona McArdle:

I guess that’d be like longitudinal work, wouldn’t it, for populations.

Adam Smith:

And then her recommendation at the end was to look at what interventions, although I think we talked about this before, there are already lots of interventions to improve sleep problems, aren’t they? Because this is a-

Dr Riona McArdle:

It’s adherence though, isn’t it, really. Because you could tell me that I shouldn’t watch TV right before I go to bed, but I’m still going to do it.

Dr Astrid Suchy-Dicey:

That’s sleep hygiene. But you could do cognitive behavioural therapy.

Dr Riona McArdle:

Well, that’s what she suggested. She basically said do not take drugs and just [crosstalk 00:25:13].

Dr Astrid Suchy-Dicey:

Skip benzodiazepines.

Adam Smith:

Finding the right interventions and also as well, when to apply them, which was important. When is the right time? Is this a habit that you can form early on in life and then stick with, or do you apply it, is middle age too late? So I thought that was a really interesting talk, that was the hot topic of today.

Adam Smith:

We mentioned before obviously Professor Kim from Seoul National University’s talk.

Dr Astrid Suchy-Dicey:

I have to say, I’m actually pretty excited about the blood based biomarkers. I know that you were more like-

Adam Smith:

No, I wasn’t trying to wash over it. I found the echo in the room was quite hard to pick up on, and the slides colouring many quite hard for me to follow.

Dr Sara Imarisio:

I think the topic is very, very interesting and I think it gave again a very nice review of the literature from the 1980s to today. I think it didn’t present data that are really outstanding, but I think that probably in the different panel today, these topics were discussed more in depth probably.

Dr Astrid Suchy-Dicey:

Yeah. I think it’s been a topic that’s come up over and over in this conference though, yesterday and today. I think probably it will tomorrow as well. I just keep seeing people talking about it.

Dr Astrid Suchy-Dicey:

I actually came early specifically for a workshop on Friday on the topic and I learned a lot. I thought that was pretty neat. There were a lot of people here to present. And so maybe I’m a little bit biased, because it’s what I’m thinking about, but-

Dr Sara Imarisio:

I think it’s very important, it’s very interesting actually as a topic to develop.

Dr Astrid Suchy-Dicey:

Yeah. Well, it gets back to that objective markers of dementia and maybe specifically Alzheimer’s type dementia that we were talking about, Ri, that I need measures that are more culturally objective. I think a lot of people need…

Dr Astrid Suchy-Dicey:

The more measures you have, maybe the better.

Dr Riona McArdle:

I think it’ll be good to see with all of the kind of biomarkers that are coming out, what’s the best combination? And within that as well, what’s the most cost effective combination that can give you the best accuracy?

Adam Smith:

Cost effective. I think as well, practically applicable, particularly if we’re thinking about in healthcare and in the NHS in the UK.

Dr Astrid Suchy-Dicey:

For screening, yeah, you can’t screen people using PET imaging or CSF.

Dr Riona McArdle:

That’s one of the things with our research that maybe the blood biomarkers, if they’re more cost effective to do would be useful for as well. With the gait analysis, we often say it’s like a pre-screening tool for telling you to go get more accurate biomarkers. And that’s because it’s going to cost less to do gait assessment than it is for you to go and get a PET scan done. Doctors aren’t going to just send everyone off for a scan, but they might send everyone off for a blood test or for a gait test.

Dr Sara Imarisio:

But it’s good to know there is an appetite because obviously people start realising there is hop in these blood biomarkers. We just have to optimise and to minimise the background signal that you can get from-

Dr Astrid Suchy-Dicey:

Yeah, and develop understanding of what the limits are and to utilise, know that what those limits are in clinic, keep those in mind. It is a screening measure. It’s not necessarily a diagnostic measure, a hard diagnostic…

Adam Smith:

And he said that their ultimate aim was to have an 80% accuracy rate from that. And I can’t help but think we talked about this yesterday on biomarkers, where there are actually, what you’re going to end up with is back to that combination. It won’t be a single thing, it’ll be, you can increase accuracy from… I don’t know what percentage accuracy they’re at, at the moment, but-

Dr Riona McArdle:

I think it was 0.8 with the cerebral spinal fluid combination that you presented on yesterday. But I think it’ll be a toolbox.

Dr Astrid Suchy-Dicey:

It’ll have to be. The positive and negative predictive values for an 0.8 sensitivity or specificity is not that great.

Adam Smith:

That comes back to that same argument then about what’s the benefit of that diagnosis? Spending the money on that and giving that. You can understand if there are treatments out there and you want to give the right treatment to the right people, or if you’re looking for research participants and you want the right peer pulled for your trial, but actually are the care interventions there? Does it really make any difference too much?

Adam Smith:

Because the same treatment you’re going to get in terms of care and support is the same whether it’s a milder or more severe form of Alzheimer’s, or whether it’s FTD, as opposed to-

Dr Riona McArdle:

I would argue that if you’ve got different types of dementia that this will obviously affect the drug studies that go on if you’ve got an Alzheimer’s disease group, but actually half of that Alzheimer’s disease group or a third of that Alzheimer’s disease group have got dementia Lewy bodies and your drug treatment doesn’t work because it’s masked the effect.

Adam Smith:

One you’ve got the treatments.

Dr Riona McArdle:

But I would also say that for care and prognosis, the kind of dementia you have will progress at a different rate. And will have different symptoms at a different rate that might need to be managed differently. I think that for the management techniques, you do need to know what type of disease a person has got.

Dr Riona McArdle:

I think that having a differential diagnosis will still be useful. I would also say differential diagnosis, although we don’t have drug treatments that we can give people that are going to stop the disease, there is drug treatments that certain diseases like dementia with Lewy bodies are very sensitive to. So you wouldn’t ever give them those. And you don’t want to find out someone has got a disease like dementia Lewy bodies by giving them an anti-psychotic drug and making them much worse.

Dr Riona McArdle:

So it’s to prevent things like that happening.

Adam Smith:

Also as well when we’re starting to look back, so often now with the longitudinal studies, when we’re looking back over lifestyle and the different factors that we’re doing, knowing exactly what it is you do have now with the right sensitivity and biomarkers is important then, because we can answer those questions moving backwards.

Adam Smith:

Okay, so we’re really getting tight on time already. I haven’t asked you yet about the talks that you saw that particularly interested you over and above your own talks in the highlights. So Sara, was there anything particular that you wanted to highlight that’s interested you today?

Dr Sara Imarisio:

Yes, so I’ve been to two series of talks. One in the morning that really interested me was preclinical drug discovery for sporadic Alzheimer’s disease, biological pathways. And mainly the various talk started from the genetic components. So what we learned from the genome wide studies and the discovery of new genes that highlight new pathways involved in causing the pathologies.

Dr Sara Imarisio:

One of the talk was from Jessica Young. And she talked about the role of Sorrell one. So she studies the role of the early enzyme pathway in causing the pathology. So she gave a very good overview on how important it is to look at the early enzyme pathway in order to understand better the pathology, and what are the implication in increasing the pathology and the accumulation of AB tau. So she gave a very interesting talk.

Adam Smith:

Do you know where she was from? Was that in your notes, if people want to look her up?

Dr Sara Imarisio:

Yes, she was from the University of Washington. And she’s working on IPS cell derived from human induced IPS cell, both as a two dimensional assay as well as an organoid. And so she gave a really, really nice overview, probably because I’m really attached to the idea that actually the endozome is playing a major factor in causing accumulation inside the cell, and how the dysfunction of the enzyme could have an implication.

Dr Sara Imarisio:

So she showed very neatly that actually the phenotype with Sorrell one deficiency is resembling very much what you see in Alzheimer’s disease. So there is obviously similarities between the two pathways.

Dr Sara Imarisio:

Another interesting talk was again, correlating what was identified in the [inaudible 00:33:35], in particular, sorry, the lipid metabolism. And so this guy is Rik van der Kant and he was talking about how cholesterol is actually implicated in causing the neurodegenerative diseases. And especially, he was looking at AB and tau. I think that it was a nice way to bring together what we learned from the genome wide study and these new avenues of research, and to show how people are starting studying them, and how people are starting developing drug discovery strategy to target this new potential pathway.

Dr Sara Imarisio:

So that for me was encouraging. Again, it’s a sign of hope that we are going to make breakthrough.

Adam Smith:

Fantastic. Thank you, Sara. And we should add, obviously, I’m going to go around and ask other people the same, everybody else the same question now. But if you’re out there and you’re working on, if you’re working in similar fields here, we’re always very happy to share blogs and posts through our website. Please do comment on the podcast, and share your own work too, because I think one of our roles and one of our aims of the website has been to encourage more collaboration, particularly across people from different countries and work in different areas. So please do, if this is a field you’re interested in as well, share and let us know.

Adam Smith:

How about you, Astrid?

Dr Astrid Suchy-Dicey:

Yeah, actually, this afternoon, I saw session on vascular contributions to dementia. I actually come from the field of vascular epidemiology. I was really interested to, vascular dementia and vascular pathology is really important in the population that I study in. I was really interested to see some talks on that.

Dr Astrid Suchy-Dicey:

And back to this one biomarker, I was really excited to see a talk that was showing really neatly that neuro filament heavy chain was strongly correlated to small vessel injury, and could potentially differentiate from neuro filament light chain, which is strongly correlated to neurodegenerative and Alzheimer’s disease. And so I thought it would be neat if you can measure both of those and use them to split apart vascular and Alzheimer’s dementias, which of course have a lot of overlap.

Dr Astrid Suchy-Dicey:

But all of the talks in that session were great. That talk was given by Atticus Haynesworth, who I think might be… definitely UK.

Dr Sara Imarisio:

Yes, he’s UCL.

Dr Astrid Suchy-Dicey:

It was done by Adam… And I didn’t catch his last name, but he was a medical student, and is apparently giving his exams right now to graduate and was unable to attend for good reason.

Dr Astrid Suchy-Dicey:

And this morning, I saw a neat talk in an area that I know much less about by Zachary Miller from UCSF. And that was on neurodevelopmental and environmental factors related to age of onset of Alzheimer’s disease and separating-

Dr Sara Imarisio:

Did he talk about air pollution?

Dr Astrid Suchy-Dicey:

I don’t think air pollution, it was more person factors. So handedness and education and a number of different personal characteristics. But I think that there were a lot of different things that he was looking at, but different factors that distinguish early onset Alzheimer’s from late onset.

Dr Astrid Suchy-Dicey:

And he was suggesting that early onset could even be defined as younger than 70, rather than younger than 65. Because the younger than 70 group has characteristics that are more alike than the older than 70. And that might be better a definition and if that’s the case, then should we go back and, reconsider other early onset, late onset studies that have been done? Because of course that would change a number of trials and studies.

Adam Smith:

And this is interesting, because in the UK, there’s been a big push from government to improve early diagnosis rates and it has had an impact. I think the diagnosis rates are over 65% now. And whereas we used to see people get their diagnosis in their early 70s, having lived with symptoms for a very long time, before they went to a doctor’s, they encouraged the other works of the charities and government and doctors, GPS, encouraging people to come and talk to them about memory problems.

Adam Smith:

We have seen the diagnosis move into more like late 60s now.

Dr Astrid Suchy-Dicey:

It seems like the pathologic course might be different from people that have that earlier onset, that they might be more characterised by, he said, left handedness, which I thought was very disturbing, because I’m left handed.

Adam Smith:

Is left handed a risk factor?

Dr Astrid Suchy-Dicey:

Being left handed is maybe a risk factor. Having seizure, autoimmune and non-amnestic characteristics that maybe define early onset, whereas late onset is characterised by more traditional risk factors, that I think we’re all familiar with like, hypertension, diabetes, cholesterol, obviously age.

Dr Astrid Suchy-Dicey:

And so I thought it was a really interesting talk. I hope the paper comes out soon, so I can read it over and really absorb it.

Adam Smith:

We’ve said this before, I think what’s fascinating about this conference, is there’s so many different topics going on all at the same time. So there’s always something for everybody, no matter what your particular interest is. Ri?

Dr Riona McArdle:

I’ll just briefly touch on two areas that I found really interesting today. I went to the dementia care session. And what I found really interesting about that was it opened up a discussion about decision-making and people with dementia, and how they can be involved in their own decision-making or what happens if they’re not involved in their own decision-making and how caregivers treat that or affect that.

Dr Riona McArdle:

And there was quite an interesting talk as well on how the caregiver management strategy, so in that some people are active caregivers and really get up and go caregivers. Other people are quite critical caregivers, who are maybe a bit more frustrated and more likely to tell a person that they’re doing something wrong, rather than letting them try to figure out how to do it right. How those different management techniques can affect the clinical information that people get.

Dr Riona McArdle:

So basically, people who are more critical caregivers will give lower activity of daily living scores for a person with dementia than a person who’s more active and might be more willing to allow the person to take the time to do the thing by themselves. I thought that was an interesting thing that we should be thinking about in the research as well, that subjective aspect. And also how we could try to maybe facilitate care giving to help people live the best lives that they can live.

Dr Riona McArdle:

I also went to a really good talk by Kia Young today, who’s looking at PCA, that is postural cortical atrophy. So he is a UCL research fellow who I think is funded by the Alzheimer’ Society. And there was two things that I liked about this talk. The first was that he was looking at PCA, which I think is an under researched area of dementia. But he also was looking at how their visual perceptual problems shaped their functional capacity.

Dr Riona McArdle:

And so he did some kinds of abstract testing. The one that I was particularly interested in was, when he looked at their balance problems in relationship to when they were using visual information, and when they weren’t using visual information. As in they had their eyes shut or they had something masking their eyes. And he found that when they weren’t using visual information, their balance looked pretty similar to the out of controls and that of people with typical Alzheimer’s disease.

Dr Riona McArdle:

But when they were using visual information, they didn’t seem to be interpreting or using that information to help them maintain their balance. Their balance looked much worse than the controls or people with typical Alzheimer’s disease. And although that finding might seem a bit abstract, he showed this great video to pull it all together at the end, where he looked at a person with PCA trying to sit down on a chair.

Dr Riona McArdle:

And it’s a video of the person trying to sit on the armrest and they can’t understand where it is in space that they need to be sitting down. And so they’re struggling to get into the chair. And it just shows how that non-understanding of visual and sensory information is impacting their functional ability to carry out just normal activities of daily living, that they might otherwise have been able to carry out.

Dr Riona McArdle:

So I thought that was a really interesting talk. I thought that the way that he pulled it together from the science, right back into the clinical translation of that was excellent.

Adam Smith:

There’s a lot of PCA research at UCL, Sebastian Crutch does a lot there and Anna Volkmer, who’s one of our regular contributors in terms of podcasts and blogs, she’s a speech and language therapist.

Dr Riona McArdle:

It’s an impressive sample that they’ve got there.

Adam Smith:

PCA has been there. They’ve had groups before, and they’ve got some particular panels and things and support group that I think Chris Hardy is involved with as well, who’s hosted some of our podcasts in the past. And getting evidence, because I think for a long time, as far as I understand it, they’ve known what interventions, particularly environmental ones could help people with PCA. But they’ve been working quite hard on getting the evidence to support that things like moving patterns and introducing contrast between toilet seats and bathrooms and things like that can help.

Dr Riona McArdle:

Yeah, simple situations.

Adam Smith:

Absolutely. I’m afraid that’s all we’ve got time for. We’re at 43 minutes. But thank you very much. Have you all got plans for this evening? There’s the ISTART membership drinks this evening.

Adam Smith:

Do you know what? I had on the list a whole bunch of other things, because there was the ECR coaching breakfast this morning, and there’s been training sessions for people. In fact, as we look around the room, there’s a big slide behind us that says common causes of rejection. I know that they’ve been looking at writing-

Dr Riona McArdle:

The Alzheimer’s and dementia gave a talk for two hours on why you might get rejected from a journal.

Adam Smith:

We’ll read out what the science says, this is an interesting research question. Inadequate methods, data does not support conclusions, analysis does not adequately address the research question, over interpretation of articles not matched to the journal. So just take on board that. We don’t need to cover, we’re just going to read the slide that’s in this room that we’ve found to do the talk.

Adam Smith:

So, thank you very much to all our panellists, Sara, Astrid, and Ri for joining us today. Enjoy your evenings. Do you know what? I’m just going to say you’re all on social media. But having read Astrid, your profile, you’re not, are you?

Dr Astrid Suchy-Dicey:

Well, I’m on LinkedIn.

Adam Smith:

You’re on LinkedIn.

Dr Astrid Suchy-Dicey:

I’m afraid of Twitter. It seems too political.

Adam Smith:

It’s fine. So we will share this via social media as well, so you can pick up all those names. So thank you very much. It’s time to end today’s podcast. Please remember to subscribe and leave a review on our podcast through SoundCloud, iTunes and Spotify. Tell your friends and colleagues and please do come back tomorrow to listen to day three, when we’ve got a whole new panel talking about what we’ve learned from there.

Adam Smith:

So thank you very much everybody for sharing your reflections on the conference. You can also see what else is going on, on Twitter, using the hashtag, #aaic19. Thank you very much. Thank you everybody.

Dr Sara Imarisio:

Thank you.

Dr Astrid Suchy-Dicey:

Thank you.

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.

END