Podcasts

Podcast – AAIC 2020 – Day Two

Hosted by Adam Smith

Reading Time: 40 minutes

This week we are recording a daily podcast, sharing all the news and highlights from this year’s Alzheimer’s Association International ‘Virtual’ Conference.

Day Two “Biomarkers”

Adam Smith is joined by Dr James Quinn, Research Fellow, from Massachusetts General Hospital, Rory Boyle, PhD Candidate from Trinity College Dublin and Courtney Kloske, Doctoral Candidate at the University of Kentucky.

Check back at this time tomorrow for news from day two, and checkout the twitter feed with #AAIC20 to find more, remember all the content from AAIC20 is available on-demand for 30 days after the conference for those registered while the conference is running, and 60 days for ISTAART member. Visit https://www.alz.org/aaic/registration.asp

You can now find our podcasts on your preferred smart home speaker – just ask it for the “Dementia Researcher Podcast”


Click here to read a full transcript of this podcast

Voice Over:

Welcome to the NIHR Dementia Researcher Podcast, brought to you by DementiaResearcher.NIHR.ac.uk, in association with Alzheimer’s Research UK and Alzheimer’s Society, supporting early career dementia researchers across the world.

Adam Smith:

Hello. I’m Adam Smith, and I’m delighted to be hosting this podcast for the NIHR Dementia Researcher website. I sound particularly northern today, I don’t know. Am I putting that on?

Adam Smith:

Today, I am joined by three amazingly talented early career researchers, bigging them all up there, to discuss day two of the Alzheimer’s Association International Virtual Conference. With so much content to take in, and the chance to go back and watch again, what we’re going to do today is share our favourite talks from the day, so that we might highlight something that you have perhaps missed or inspire you to take a look.

Adam Smith:

It’s a little bit different, because usually the audience for these podcasts are people who haven’t managed to actually make it out to the conferences, but this year everybody can attend, which is fantastic. So I’d like to welcome first timers. We have Rory Boyle, who’s a PhD candidate from the Whelan Lab at Trinity College Dublin, researching neuroimaging and cognitive reserve, and whose name apparently means red headed king.

Rory Boyle:

Yep, it does.

Adam Smith:

We also have Courtney Kloske, who is a doctoral candidate from the University of Kentucky, reading neuro information in Alzheimer’s disease, who also has a very successful side hustle in dancing, I believe.

Adam Smith:

Is that something you still do, Courtney?

Courtney Kloske:

No, I grew up doing it so I started when I was three and continued til I was about a junior in college, but I haven’t kept up with it in grad school. I still have my ballet shoes in my apartment though, so.

Adam Smith:

So you could take it up at any moment?

Courtney Kloske:

Yes, I could go put them on right now and do some ballet for you.

Adam Smith:

Fantastic, well we could always flip his to make this a video version of the podcast, if you’d like to don a tutu?

Courtney Kloske:

Yep.

Adam Smith:

And Rory, although as much as you’re the red headed king, you actually have black hair. So, that [crosstalk 00:02:12]-

Rory Boyle:

Yeah, no but I have a cousin called Rory who has red hair, so yeah. Growing up I was called, my family called me Rory dubh, which means, confusingly in Irish, or [inaudible 00:02:24] Gaeilge, red haired king with black hair. My cousin with red hair was called Rory rua, which means red haired king. So, not a lot of sense made there but yep…

Adam Smith:

Is that the equivalent of calling you the slim guy, fat. And fat guy slim?

Adam Smith:

[crosstalk 00:02:42] I can say that, as the fat guy.

Rory Boyle:

Yeah, I think my mam was just copying my auntie, she liked her nephew’s name but they never copped on that I would never have ginger hair, so didn’t really work out.

Adam Smith:

Well, thank you very much Courtney and Rory as our first timers. And we do also welcome back expat, Dr. James Quinn who is a research fellow at Massachusetts General Hospital, researching the role of neuropeptides, and precision medicine.

Adam Smith:

Is that still the case, James? Because you’re a man of many talents, you’re always looking at new things. Is that still your field?

Dr James Quinn:

Yeah, so definitely what I’m mainly focusing on is predominantly neuropeptides, really why they’re getting dysregulated in dementia and whether they can be a potential biomarker and their PG target.

Dr James Quinn:

So, it’s really my area of expertise at the moment.

Adam Smith:

And I feel like I’ve not suitably picked on you with, we’ve got Courtney with her dancing [crosstalk 00:03:37]-

Dr James Quinn:

I can’t dance. I can’t dance.

Adam Smith:

Rory with his red hair, I can’t pick on you in any other way other than, I imagine, everybody else picks on you there in the US for your accent?

Dr James Quinn:

Somewhat. My parents got very annoyed when I said, my girlfriend will attest to this, when she had a lovely, I need to get this right… So, a basil plant. But I said basil to my parents, my parents basically disowned me at that point in time.

Adam Smith:

Seems very reasonable. Do you get annoyed with all your colleges walking in and going, “Do you want a cuppa tea James?”

Dr James Quinn:

I’m the one offering to make them tea, so I feel like that’s how I’ve made friends here. But, I do remember when I came for my interview I brought Scottish shortbread, I mean it was close enough. But that went down really well, so I think sometimes you have to embrace the stereotypes a little bit.

Adam Smith:

Well, I think that’s enough bullying of everybody.

Adam Smith:

This, of course, is your third AAIC recording with us, James. So I remember in our very first one, you were very critical of a certain researcher that’s just been made a full professor. Going, “They’re not the young ones anymore, we are.” And of course now, James, three years in and fellow, you’re one of the old guard now, you’re not one of the young people anymore.

Dr James Quinn:

I know, it all went wrong Adam. I keep coming back, but I think the podcasts are really good, I remember every year I’ve taken part and then as soon as the conference ended, I’ve just listened back to all of them. Kind of in a row, and it is a really good way of kind of finding out what early career researchers as well as mid-career, senior investigators think of what is going on at the conference.

Dr James Quinn:

It’s a lot easier to listen to a podcast than a talk.

Adam Smith:

Well that’s very kind of you to say so, and thank you very much everybody for coming down here and joining us. And I think this is the first time, as well, where all the panellists are people who are aren’t resident in the UK right now, so that’s another first for us as well, so the less serious introductions aside, maybe we should move onto the more serious introductions.

Adam Smith:

So Rory, could I ask you to properly introduce yourself?

Rory Boyle:

Yeah, no problem. So my work focuses on the development and validation of neuroimaging measures of brain health, but primarily cognitive reserve. So, probably most of you are familiar with the concept, but cognitive reserve is a construct that can explain how some people are able to maintain their cognitive function despite having significant levels of pathology, or despite experience brain ageing.

Rory Boyle:

So, it’s a really potentially powerful mechanism because ultimately if you can figure out how to enhance cognitive reserve, you might be at one stage able to slow cognitive decline, or able to maintain function in people who have high levels of Alzheimer’s pathology. But I suppose the focus of my work is that we don’t really have a solid way of measuring cognitive reserve. So, I’m using structural and functional MRI data, alongside cognitive and social behavioural data to try and develop an objective neuroimaging measure, and we’re using machine learned techniques to apply to these data to try and develop a robust, generalizable measure that hopefully, or it better be, accurate across multiple data sets.

Rory Boyle:

So, that is what my work is looking now.

Adam Smith:

That’s really interesting, thank you Rory. And you know, it’s funny enough you should mention that. Because that’s something that too occurred to me yesterday is, so much of what we see and hear at the conference is looking at the disease itself, rather than looking at the people without the disease to understand why they don’t get it, as opposed to why people do.

Adam Smith:

And I don’t know, it’s just interesting that the focus seems to be on the disease rather than people without the disease.

Rory Boyle:

Yeah, yeah. And I sort of I suppose it’s a bit more of an optimistic way of looking at things as well, so it’s not all doom and gloom.

Adam Smith:

And to play to those stereotypes again, that’s the Irish way, right?

Rory Boyle:

It will be grand.

Adam Smith:

And Courtney, can I come to you next?

Courtney Kloske:

Yeah, so I do neuroinflammation and Alzheimer’s disease research, and I specially look at how the APOE ISA forms impact neuroinflammation in Alzheimer’s disease, so definitely a big growing topic right now. And the way I’m approaching this is in a broad sense, so I’m doing a lot of work on human atopsy tissue, from the Sanders Brown [inaudible 00:08:10] ageing brain bank. And I’m comparing APOE3 and APOE4 patient samples to just get a broad sense of their neuroinflammatory panels and profiles in their brain. Moving from RNA to protein, and then looking at the histology in the tissue, and then kind of taking all of the things that I’m finding in the human tissue, and targeting neuroinflammation pathways in mass models, looking at how the APOE ISA forms impacts specific pathways.

Adam Smith:

That’s really interesting, and funnily enough, Dr. Lindsay Sinclair, who did the podcast with us yesterday, works in the south west UK brain bank. And that’s her field as well. Do you get brain tissue from the UK brain banks? I know they ship it all over the world as well, don’t they?

Courtney Kloske:

We might, but the brain bank that we have in Sanders Brown is pretty extensive, so I think that all of my work is done in house but I can imagine other people in the centre getting stuff from abroad.

Adam Smith:

Well, just a plug for the UK there, the UK brain banks are quite happy to supply brain tissue elsewhere.

Adam Smith:

And James, we’ll come to you now.

Dr James Quinn:

So yeah, I did my PhD in the UK at the University of Manchester, working with Professor Nigel Hooper and Dr. Katherine Kellett. And there I was looking at tau proteolysis, and that’s a post translation of one application of tau. How that can be a potential biomarker of different types of tau, so things like Alzheimer’s disease, [inaudible 00:09:38] generation and progressive supranuclear palsy. After completing my PhD, I moved to Mas General Hospital, to work with Dr. Becky Carlisle, and Dr. Steven Arnold, where they have got some exciting preliminary data, looking at neuropeptides, the signalling molecules in the brain. Pretty similar to neurotransmitters.

Dr James Quinn:

And essentially showing that they could be really good biomarkers of synaptic health, as they’re picked up in both brain and CSF. So my project is really just to go and do a deep dive into these neuropeptides, see if we can improve them as a biomarker, potential therapeutic target and understand what’s going wrong, in the disease.

Adam Smith:

Okay, so the focus for today’s session was biomarkers. So before I go to each of you to ask what your own highlights were, perhaps we can talk about what the Alzheimer’s Association trailed as the main plenary sessions.

Adam Smith:

Rory, did you attend the imaging biomarkers AD prevention plenary?

Rory Boyle:

Yes, I did.

Adam Smith:

With Susan Landau?

Rory Boyle:

Yeah, so it was a really great, interesting talk. There was a whole lot covered, so I suppose I’ll try and give a brief overview, but yeah Susan started off talking about how, comparing different amyloid and tau profiles that you can discover based on PET imaging.

Rory Boyle:

She just sort of, a couple of facts she pointed out that I found really interesting, were that one in five people at the age of 90 years old who are diagnosed with Alzheimer’s are actually amyloid negative, based on PET imaging. And then while tau can be, or is associated with amyloid positivity, a third of people who are amyloid positive actually have tau levels in the normal range. So I suppose Susan pointed out from the discrepant findings that pathologies other than just amyloid and tau can explain substantial amount of cognitive impairment.

Rory Boyle:

And then I suppose, the next thing Susan focused on was how drug trials tend to focus on enrolling people who are actually cognitively impaired, right now. To see if the kind of the cognitive treatments or drugs can reduce impairment, or slow decline. But there’s the argument that the pathological effects might be too deep rooted at that stage, to maybe reverse decline or slow decline.

Rory Boyle:

So, Susan was emphasising that it’s really important to identify biomarker profiles of cognitively healthy people as well, so that these individuals can also be used in treatment or prevention trials at earlier stages. And I suppose that’s where Susan then sort of switched focus to prevention. And she talked about the US POINTER study, so sort of the US analog of the FINGER trial from Finland. Which found that a two-year intervention, or multi domain intervention, comprised of an exercise intervention, a diet intervention, cognitive stimulation, and sort of self-monitoring of your heart health, was found to have a protective effect in cognitive function.

Rory Boyle:

And Susan, I think, is maybe the lead of the US POINTER study. So she was describing their goals, she said, “Our goal is to investigate whether that multi domain intervention will have the same effects in the US.” But they’re also collecting really rich neuroimaging data, so they’d be able to look at the neuromechanisms underlying these de-cognitive protective effects.

Rory Boyle:

And they’ll be able to ask whether lifestyle factors can protect cognitive function. Via, say, effects on vascular pathology or Alzheimer’s pathology. And they’ll also be able to look at whether PET imaging measures of amyloids or tau, or other neuroimaging measures that baseline are able to predict individuals who respond best to interventions. So, I suppose then you could target treatments maybe at these individuals as they’ll stand benefit most treatments, so that was a really nice overview of the POINTER study, or other goals. And I suppose to close, the take home message that Susan made which was really nice was that to optimize Alzheimer’s treatment and prevention, it’s all about matching the right participant or participant group, to the right treatment strategy at the right time. So I thought that was a nice easy to understand and fairly clear take home message from the talk.

Adam Smith:

And that’s a message that’s come through loud and clear a few times now, hasn’t it? In various different things-

Rory Boyle:

Yeah, yeah.

Adam Smith:

Is, it might not necessarily be the drug that’s at fault, but it’s the wrong people at the wrong time rather than an ineffective treatment.

Adam Smith:

I attended this session as well, I have to say she got through a lot of content in a short space of time. I was struggling to keep up, I may have to go back and watch that one back.

Rory Boyle:

Yeah, I definitely will too. I was typing notes one handed so I was fair bit slower as well. But yeah, there was a huge amount of content but in fairness, it was really clearly presented as well so…

Adam Smith:

Absolutely, it was. I think it was a great talk, it’s one I think you can watch back a few times and I think you’ll get something new from it each time. And I should add, that you normally don’t type notes one handed, right? It’s because you’ve got a dodgy shoulder right now.

Rory Boyle:

Yeah, well it’s my bad hand as well, so I don’t normally type notes at all maybe, but yeah. Bit slower this time.

Adam Smith:

So, James and Courtney did you watch that one too? Did you have anything to add to Rory’s summary?

Courtney Kloske:

Yeah, I watched it as well and I thought it was a great talk and I agree that, she crammed a lot of information in there but it was very well presented. As somebody who does not do neuroimagery, and was able to understand most of the talk. And kind of going off of what you’re talking about with the pointer study, and targeting the right groups, it’s something that I’ve heard before but it’s something that I liked how she said it, was the people that have amyloid positive, they’re amyloid positive in their brain, but they might have low tau. That, when we’re targeting them for certain clinical settings, and everything that we should try and focus on what else is present in their brain, she was like, “If they’re amyloid positive and low tau, they could have vascular pathology that, if we could treat that we could help all other symptoms as well.”

Courtney Kloske:

And so I think hitting that at multiple points instead of just saying, “You have Alzheimer’s disease.” And only targeting that, I think that that was one of the ideas that I really took away from the talk.

Adam Smith:

Yeah, absolutely. Good point. What about you James?

Dr James Quinn:

I agree with what Courtney said and what Rory said, but I thought it was a very good example of precision medicine based approaches, and I really like the point she made about one of the clinical trials, and back in 2015 that was a failed anti amyloid trail. But 36% of the patients they had in that trial were amyloid negative. So it was anti amyloid drug, and testing on 36% on these patients who don’t have any amyloid pathology in the first place.

Dr James Quinn:

So I thought that a real kind of key take home message, that we have to be looking at patients with a much more holistic view. Take into account all of the pathology that’s in the brain, and also all the different environmental factors that can play a role and also looking for those kind of easy hits that we can make. So, let’s say they’ve got a big vascular build up, we can look at treating them a statin, instead of going down this approach of only focusing on one drug to cure Alzheimer’s disease, which is never going to happen.

Adam Smith:

And that’s tricky as well, isn’t it? Because I think pharma companies have to consider carefully the screening and screen failure costs, which has upped the ante on getting the right people into the right trials, but also at the same time the screen fills go up, because they’re looking for amyloid, or they’re having to look for amyloid before they decide who to enrol into the trials. Which has put the costs up.

Adam Smith:

And so, I think it’s tricky finding the right people for the trials as well, which has driven the costs up as a result, I’m not quite sure what [crosstalk 00:18:03]-

Dr James Quinn:

That’s the perfect transition to the next talk.

Adam Smith:

It is, which I’m going to come to you about actually I think James. So, you attended the blood based biomarkers session from Charlotte Teunissen. What did you learn?

Dr James Quinn:

Yeah, so Charlotte Teunissen is one of the big players in the Alzheimer’s disease biomarker field, so she is based at the Amsterdam centre. And essentially, she really just gave tour de force overview of plasma tau, A-BETA, [inaudible 00:18:40] NFL, as potential AD biomarkers. She also mentioned this pre-screening idea, that they were able to by looking at plasma amyloid, they were able to rescue the number of lumber punctures down from 434 to 220 lumber punctures, to get 100 patients in clinical trial.

Dr James Quinn:

So I thought that was a really nice example of using plasma biomarkers in order to reduce number of LPs, because LPs take a long time. They’re like an hour. And also they can be perceived to be invasive.

Dr James Quinn:

So, that was a really good analogy. And she kind of talked a little bit about the two test she’s developed. So within the group, they’ve developed their [inaudible 00:19:24] anti amyloid approach to meeting a [inaudible 00:19:28] which is this kind of very fancy technique, but it’s essentially a big multi-plexilizer, that takes place in individual beads within a well, so you can have multiple wells with different antibodies on it. And you can get ultrasensitive detection.

Dr James Quinn:

So, for example, NFL you can just tech down to like three peakagrams, whereas in [inaudible 00:19:50] you can detect 70 nanograms. So, we’re really getting to extremely high levels of sensitivity.

Dr James Quinn:

So, she talked a little bit about that and how they have been able to multiplex these AD biomarkers to the GFAP, which is a marker of astrocytes. NFL, which is a marker of accidental damage, and then amyloid. And she showed in lots of different cohorts what was going on. And yeah, it was just a really good talk.

Dr James Quinn:

And also talked a little bit about pre analytical protocols to reduce variability. Showing that amyloid left at room temperature for 24 hours decreases, but in a fridge it’s stable, and this sort of thing. So it’s really just showing that blood based biomarkers now are at a point which we can use in clinical, well I wouldn’t say clinical practice but in research practice. In order to improve the patient recruitment into clinical trials. But yeah, I mean I could talk about this forever so I’ll let you move on to another.

Adam Smith:

Well, it’s the holy grail isn’t it? Blood based biomarkers, the holy grail that comes up. I mean certainly I think it’s come up at the AAIC for three, four years now. And it always just seems to be on the horizon. It just, oh wait we’re nearly there oh…

Adam Smith:

I don’t know, I mean you get a sense every year that we come back, it’s getting that much closer. I guess we just have to hope this time next year we’ll be there, or not we but the community will be there because this isn’t just something that one group is looking at, of course, is it? And I should get a plug in here, there’s a whole professional interest area part of ISTAART, which is specially for blood based biomarkers, and anybody interested should join that PIA, and we had Henrik doing a podcast with us last week, who talks about this very eloquently and passionately. So please do look through our archives to find that podcast.

Adam Smith:

Did anybody, Rory, Courtney, did you have anything to add on that session from Charlotte?

Rory Boyle:

No, I didn’t get a chance to listen to it unfortunately, it was my dinner time at that stage.

Adam Smith:

I love the idea, you took a lunch break.

Rory Boyle:

Dinner [crosstalk 00:22:06]-

Adam Smith:

Dinner. What about you Courtney?

Courtney Kloske:

I was able to watch it, and after that talk I just felt like everything just exploded in the field because she was talking about 217, the [inaudible 00:22:21] 217, and then the next talk an hour later, then the paper came out. So, my brain is on overload with this stuff right now, but I was just fascinated by the talk and it was a good lead into the rest of the talks for the day and that paper.

Adam Smith:

Absolutely. I know I’d prepared all of you suggesting things that you might want to go to, and one of the other things I suggested which was the very last of the live sessions today, which was the leads, L-E-A-D-S, not Leeds from Yorkshire who just got promoted to the Premiership.

Adam Smith:

Sporadic early onset, AD in the spotlight session. Did anybody actually manage to get to that?

Dr James Quinn:

I could take this one again [crosstalk 00:23:08]-

Adam Smith:

Go, James.

Dr James Quinn:

It was super interesting. I don’t think there’s too many cohorts that really focus on this early onset Alzheimer’s disease outside of the known [inaudible 00:23:19] in mutations, APP mutations. So, it is essentially a cohort where they are looking at early onset Alzheimer’s disease, so anything before the ages of 65. And they just, it was definitely early stages with the cohort. They had some kind of concrete data, but they really just laid out their plans, what they’re going to be doing over the next four years, the cohort. And then the plan is to then translate that into a therapeutic unit. Therapeutic arm, where they can test novel drugs in this cohort.

Dr James Quinn:

It was really interesting, they kind of broke down clinical criteria. I think if you are interested, it’s definitely one to watch. I don’t think I could do a good enough job of summarizing what was said, because it was looking at MRI data from the cohort. It was looking at clinical demographic data from the cohort, so it’s not really something you can really explain but it’s just a really interesting cohort and it’s kind of spread throughout the US and they are planning on taking it international as well. So it could be really exciting for the future.

Adam Smith:

And there’s a few people working in that space, isn’t there? I’m thinking particularly of people like Craig Ritchie, with the prevent trial. And Clive Ballard with protect as well. Just thinking of the UK examples, I know that there are others in the US, and elsewhere in the world as well. Thank you very much, James.

Adam Smith:

So, Courtney, I’m going to come back to you because of course with so many posters, so many online sessions, on demand sessions, live sessions, and biomarkers being such a vast topic, tell me, what talks and posters caught your particular attention today?

Courtney Kloske:

So, I have not gotten to the posters yet because there were so many other talks that I wanted to listen to, so I’m getting to the posters later. But for the talks, my favourite one for the whole day of all the sessions in it was the role of microglia activation in the development of amyloid and tau pathology. So, there are four talks in that session and they were all just very fascinating, kind of talking about targeting microglia phenotypes in a different way than I would normally expect and kind of in more of a biomarker idea. So I would suggest going to check out all of those.

Courtney Kloske:

There was one specifically on higher trim two levels, and microglia activation associated with a slower rate of amyloid PET, increase in human and transgenic mouse models of amyloid data. And it was by Michael Ewers. I don’t remember where he is from, but his was one of the four talks and it was really great so I’d recommend checking those out.

Courtney Kloske:

There was one that I really liked that didn’t really have anything to do with biomarkers today, it was from Lee Goa at Harvard on sleep disturbance and [inaudible 00:26:20] in Alzheimer’s disease, and in this study they followed patients for 12 years and looked at their self-reported data. And I was really fascinated by their findings saying that if you have, if you sleep more than nine hours your likelihood of having Alzheimer’s disease, or developing Alzheimer’s disease, increased. And in my head I’m always telling people you need to get as much sleep as you can, whereas I think instead you have to find that nice balance.

Courtney Kloske:

And they did talk about a potential mechanism in there, so I think future studies in that will be really fascinating.

Adam Smith:

Yeah, I attended that one. It was a watch, was that? It wasn’t poster, yeah. So I went to that one too. I found that talk really fascinating too, I saw that they used UK bio bank data which particularly caught my eye because where I work, at UCL, has a bio bank.

Adam Smith:

And they had 502,000 people in their data sets, which is just such a huge number. Anybody who’s interested in data checks should definitely look up the UK bio bank, and given this study was taking place at Massachusetts General Hospital just shows you can access this data elsewhere in the world. And it was fascinating, so six to nine hours sleep, two per 1000 were going to go on to develop cognitive impairment. Whereas for the nine hours plus sleep it was 6.6 per 1000. So it was more than three times as likely, which I agree with you I mean who thought more sleep was better? I mean that’s not the case at all. I mean obviously it’s going to be complex, there’ll be more factors to play into that I’m sure if you wanted to unpick and find fault with this I’m sure you could.

Adam Smith:

But also sleep apnea was a factor, and daytime sleepiness came into that. And there was another sleep study, I don’t know if you picked up on, today as well that was talking about more frequent napping through the day was another risk, another potential biomarker as well, looking at sleep patterns through the day. I’ll have to go back through my notes.

Adam Smith:

Anyway, sorry. I interrupted you, but yeah I found that very interesting too. What else did you see?

Courtney Kloske:

EEG talk, the valuable tool to do screening for neurodegenerative and preclinical Alzheimer’s disease, at the Paris Brain Institute. I’m not an EEG person, so I’m not even going to try and really get into that, but it was a great talk and it really gave a nice overview of really what they were trying to do. And it does really seem like it’s a good potential way to look at neurodegeneration, their study was from the way she presented it I really enjoyed it.

Courtney Kloske:

That one I saw you had tweeted about, so I went and checked it out. So that one was good.

Adam Smith:

Yeah, do you know what funnily enough I’ve written a note here that I didn’t mention on that sleep study which something did occur to me, so if I’m a big sleeper and I know this, and I suddenly go, “Whoa I’m going to stop getting quite so much sleep. I’m going to start getting up earlier in the mornings and going to bed later at night.” Would it make any difference? I think that is a follow up study for that one, looking at if you can change sleep patterns, does it have any effect?

Courtney Kloske:

Yeah, I don’t get the full nine hours but I do get a fair amount of sleep so as soon as I heard that I was like, “Oh no.”

Adam Smith:

And also as well of course, the Mediterranean way of having that siesta in the afternoon when it’s during the hot bit, then does that offset then by that Mediterranean diet?

Adam Smith:

So, Rory, I’m going to come to you next. Could you maybe tell us what you’ve seen and heard today?

Rory Boyle:

Yeah, yeah. So actually I suppose I seen one poster got Courtney might have seen the talk related to the poster, but it was from Nico Franzmeier, in Michael Ewers’ lab. So they’re in LMU, in Munich. Ludwig Maximilian University. But yeah, the poster showed really nice results showing that soluble trend two, from CSF, attenuated the effect of APOE on cognitive decline and [inaudible 00:30:55], so it suggests that maybe soluble trend two has a protective effect for Alzheimer’s that might be a mechanism through which reserve or resilience operates, so that was personally quite interesting.

Rory Boyle:

And then I seen a really nice talk, it was part of the neuroimaging predictors of cognitive decline session. And it was from Razvan Marinescu, from MIT. I think he might also be affiliated to UCL. But he gave an overview of the results from the tadpole challenge. So the tadpole challenge is sort of machine learning, I suppose, competition where participants, 33 different teams were given a load of cognitive clinical data and neuroimaging data, including MRI, PET, DTI and CSF measures as well. And they were asked to try and predict three different type of variables, so ventricular volume from MRI data, the clinical diagnosis of Alzheimer’s around CI. And cognitional function as measured by the ADAS cog scale.

Rory Boyle:

So, I suppose not to get too into the results but what was really interesting from my point of view was that machine learning models were able to outperform random chance for predicting clinical diagnosis at follow up, as well as ventricular volume. But no model could perform better than a random guess for predicting follow up cognitive function. So, not to bring everything back to cognitive reserve, but it sort of shows the potential for cognitive reserve that there is a huge gap between neuroimaging data and cognitive function, there is something else there at play, which if we could measure better maybe we could predict these things better as well from baseline data.

Rory Boyle:

But yeah, it was really interesting and really well presented. And it was an actual academic challenge with cash prizes, so that was nice to see as well I suppose. But yeah-

Adam Smith:

Fantastic, have we covered everything else? Or was there anything else particular today you want to draw attention to?

Rory Boyle:

Yeah, I seen another really nice talk as well from McKenna Williams in UCSD, on she was presenting work from the Vietnam era twin studies, that really nice cohort where, I think they’re Vietnam veterans or from that era anyway, obviously. But she showed that an Alzheimer’s signature measure of [inaudible 00:33:42] was not able to predict progression to Alzheimer’s from mild cognitive impairment, but a signature based on grey matter meant the [inaudible 00:33:51] was able to predict regressions, so that was nice because usually just Alzheimer’s [inaudible 00:33:57] signature seems to be quite powerful, so it was sort of nice to show that maybe something else can outperform it as well, for predicting diagnosis. So I found that really interesting as well.

Adam Smith:

I didn’t see that one, but it sounds like it’s worth going to look up.

Rory Boyle:

Yeah, yeah. It was definitely worth a look.

Adam Smith:

I’m going to go to you now, James. You’ve attended everything today, right? I mean you’ve got a big list now.

Dr James Quinn:

I tried to. I think there’s three talks I kind of want to talk about. The first one was the COVID-19 talk, it was in the developing topics session. It was really interesting, it was led by a soon to be PhD student Jennifer Cooper at UVC, and it looked at GFAP, total tau, UCHL1 and NFL, and COVID-19 positive plasma.

Dr James Quinn:

And they showed that there was a high percentage of delirium in COVID, this is something that people in Mas General are looking at. And they showed that GFAP significantly increased, the total tau significantly decreased in COVID-19 versus ICU controls. And actually none of these measures significantly correlated with a measure of respiratory illness. So it shows that the neurological aspects of the disease is separate from the respiratory aspects of the disease. So I was fascinated by that, and I’m going to send that back to the people in my lab who are doing some COVID-19 work. Because it’s just very interesting to see we can detect neurological aspects of COVID-19.

Dr James Quinn:

And then the next talk that I want to talk about was the overall session about precision medicine, and there was one talk that I found very interesting. I’m sure I will get the same for you in a second, but where they’ve essentially showed that, they did all of this, they’ve made this, I think it was called a human farmer comb. Which was all of the data that’s publicly available about Alzheimer’s disease, plus all of the data publicly available [inaudible 00:35:58]. Put it together, sent machine learning to do whatever it does. And they’ve pulled out some targets, but they said they were only able to pick the targets to test further by having a cell biologist in the broom to sit down and go through the targets that were pulled out. So it was good to see that my job is going to be safe for the future, but it was a really interesting way of pulling together all other data that’s publicly available and making it so it can be used for something positive, really.

Dr James Quinn:

Let me just get the name of the presenter for you, Martin Hofmann-Apitius, but yeah. It was a fascinating talk. I’m not great with this kind of big data approach, but it was a really well described presentation. And then finally, I think the biggest news response from day has been about the tau 217 [inaudible 00:36:57] blood based biomarker. So I went to the blood based biomarker session, and as it was being presented I go the notification on my phone from the New York Times being like, “There’s a new biomarker for Alzheimer’s disease.”

Dr James Quinn:

So it was very promising. And then a lot of the other talks throughout the day were looking at this tau 217, [inaudible 00:37:16] and comparing it against tau 181, as well as the tau 231. [inaudible 00:37:27] and showing that they, they’re all pretty similar but the 217 is the best and that it was able to predict amyloid positivity, future tau PET positivity and a ton of other things, and that it is a really exciting biomarker, and a lot of the presenters were talking about how to translate this into the clinic.

Dr James Quinn:

It wasn’t one specific talk, but I can get the paper up for you. It was titled by, the first leader of it was Sebastian Palm Q-V-I-S-T, I can’t pronounce his surname, from Lund University, which as actually a plasma P-tau 217 for distinguishing Alzheimer’s disease. And that paper was released today, comparing Alzheimer’s disease against other neurodegenerative disorders. So, showing it’s very specific to Alzheimer’s disease. Again, I do not think anybody knows why all the other tauapathies and neurodegenerative disorders do not show any increases in phospho tau, when there’s clearly phospho tau in the brain.

Dr James Quinn:

But, yeah. It was a very interesting presentation. And I think, overall, it was a very biomarker heavy day. But it was a biomarker day so, to be expected.

Adam Smith:

It’s interesting, isn’t it, how these things go through trend, to use a modern term. I mean, last year at the AAIC Bart De-Stooper, stood on the stage and said, I don’t want to misquote him but he was, “It’s all about amyloid, stop worrying too much about tau.”

Adam Smith:

I’m sure he wasn’t saying tau is not relevant, but it was, “Let’s focus son amyloid.” And this year tau has been back on top, in fact didn’t Alzheimer’s Association have a specific tau conference last year as well?

Dr James Quinn:

This year, Adam.

Adam Smith:

Oh, was it this year? Sorry, this year has flown by.

Dr James Quinn:

Yeah, I know. It was probably one of the last conferences that took place, because it was back in February in Washington. A few people from my floor went.

Courtney Kloske:

Yeah, I heard it was a great conference. But yes, that was this year.

Adam Smith:

That was this year? So I went in search, I attended lots too and I went in search to try and pick out some little gems hidden amongst the posters. And I found lots. So many posters looking particularly at cognitive testing, use of cognitive testing, variations on cognitive testing, cognitive testing games. There was a particularly interesting one from Bruno Brancher from Brussels that I found was particularly interesting that’s worth a look, if people are still browsing back through yesterday’s posters.

Adam Smith:

There was an interesting one on hand dexterity as well, and using speech recognition. And I think what kind of occurred to me particularly was with all these potential for use of biomarkers in combinations, which so many of these were suggesting. Is how few of these actually then transition through to clinical practice, I think I did make this point in Twitter before.

Adam Smith:

It’s quite interesting, they all often will show some indication but never enough to be more commonly used or to find their way into mainline practice. I don’t know, would you agree with that? Disagree?

Dr James Quinn:

I just think, I’ll bring up a comment someone else made in one of the presentation. It’s going to take 20 years to get a biomarker into clinical practice, so it’s the same as getting a therapy out. It needs to go through the same level of validation, so I think [inaudible 00:41:15] talked about the first CSF COW paper that came out, CSF COW amyloid paper came out in 1996, to show that was differentially different between AD and control. And it’s probably only just starting to get into the clinic.

Dr James Quinn:

They said they do neurofilament light in the clinic, but they still don’t really do tau and amyloid, so it’s a really long [inaudible 00:41:37] process. But it would be interesting in 10, 15 years’ time to see whether there will be this massive plethora of different biomarkers out there and stuff that you can do a home instead of having to go to a clinic.

Adam Smith:

Well, which leads me nicely onto another, I’m just going to jump through mine quickly. Iona Patchie from the University of Athens had this fantastic poster about using sniff sticks. And this resonated with me because we hosted a webinar just a few weeks ago with a guy from Turan, who was talking about the old factory system and links to condition. And the relationship between able to, the sniff sticks were able to help differentiate between people who had neuropsychiatric difficulties, as opposed to a neurological disorder quite reliably. And you could see how using that would be relatively inexpensive.

Adam Smith:

It would be fairly quick and easy, potentially, to use as well in clinical practice. So I thought that had a lot of potential, I’d like to see more on that. We had of course as well quite a few posters today on gait, although many of the ones on gait looked like they weren’t loading properly. Ríona McArdle, who joins us regularly for podcasts and is joining us later in the week as well, she had a poster looking at gait combined with other things to differentiate between different dementia types, and I think that’s got a lot of potential and I’m hoping we might be able to do a podcast in future specifically looking at gait as well.

Adam Smith:

And there was also an interesting talk from Eva [inaudible 00:43:24] from Wisconsin. Really just reinforcing APOE again, as a demonstrating that people with APOE dementia, onset occurs earlier with a vaster decline. But it was just interesting data, there was 16 years’ worth of data that they based that on which reinforced what I think we know.

Adam Smith:

That was a lot to take in, wasn’t it? And we’re probably running low to time. What I am going to do though is before we move on, I do want to give you all an opportunity to plug your own talks, and I’m sure you’re all presenting, right? You’ve all got posters, talks. Is there anything you’d like to plug, Courtney first?

Courtney Kloske:

I have a poster, it’s in the basic sciences and pathogeneses button at the top. And you can just type in my name and it’ll come up, I’m the only Courtney in that group so it’s pretty easy. But it’s on the imperative neuroinflammatory response of APOE4 patients, and Alzheimer’s disease.

Adam Smith:

Fantastic, and did you do one of the awesome narrations? I’m loving the poster with narration, I’m loving that.

Courtney Kloske:

No, I did not. At the same time this poster was due I had another conference, I went to the [inaudible 00:44:40] conference. So I was trying to finish up both posters and time got away from me. But I have watched a bunch of them, and I do really enjoy it and I wish I had taken the time to make one.

Adam Smith:

Well, please do everybody go visit Courtney’s poster there. And I think if anybody gets a chance to narrate their future, they definitely should. What about you Rory?

Rory Boyle:

Yeah, so I have an oral presentation on Thursday as part of a featured research session, so the presentation is titled validation of composite proxy measures of cognitive reserve. And it’s part of the featured research session [inaudible 00:45:20] cohorts, [inaudible 00:45:22] association between modifiable dementia risk factors and the ageing brain. So that’s on Thursday at… The live chat or the live chat room is live at 11AM on Thursday, central daylight time. So that’s 5PM Ireland and UK time, so I’ll be there to take questions but I’ll be typing very slowly, so be kind.

Adam Smith:

Brilliant, thanks Rory. Is that one of the ones that’s been recorded via Zoom and then shown back as a live session with you on the screen and everything?

Rory Boyle:

No, so I’m on the screen for the actual recorded talk, but I think we’re just doing a chatroom. We’re not actually doing Zoom for the Q&A.

Adam Smith:

Okay, fantastic. Well done. And is that your first AAIC talk?

Rory Boyle:

Yeah, it is my first year here at AAIC so my only exposure before was just to podcasts, I suppose last year. So, yeah. Unusual first time, but good.

Adam Smith:

That’s brilliant, and congratulations on being able to do a talk as well. And at your first AAIC. James, are you presenting?

Dr James Quinn:

Yeah, so my poster was up yesterday but you can still access so if you go on the basic sciences and pathogeneses tab and just search Quinn, Q-U-I-N-N. Poster’s there. It is recorded, so if you want to listen to me talk about the poster you can listen, you can hit the PDF if you’d rather not listen to my voice again.

Dr James Quinn:

And then I’ll just plug the other person in my lab who has a poster, so if you go on the biomarkers and search Trombetta, T-R-O-M-B-E-T-T-A, I had to type it and spell it at the same time to make sure I’ve got the spelling right. And she’s got a poster on plasma biomarkers, using the O link, [inaudible 00:47:02] which a few people have presented on today which is this large scale looking at thousands of amyloids as a potential biomarker. And yeah, so it’s been really good to see how they transitioned to virtual. I know there’s been a few hiccups, but for the first time they’re doing a virtual conference it’s been impressive.

Adam Smith:

Yeah, that’s what I was going to just spend a couple minutes on before we wrap up. It’s brilliant, right? I mean, I have to say it could have all clearly gone horribly wrong dependent so much on technology, but I mean from my perspective I think this is amazing, I think Alzheimer’s Association have done such an awesome job to pull this off.

Adam Smith:

We shouldn’t give them all the credit, because I’m sure there’s some brilliant IT company working alongside them to make this happen. But views, Rory?

Rory Boyle:

Yeah, definitely when you throw that on top of the fact that it’s free, it’s pretty amazing especially for those that don’t have access to funding or even undergraduates or just regular people who just have an interest, they can all sign up and access as much information as we can. So, it’s really great from that point of view, so I know a lot of other conferences went virtual but still kept a fairly hefty registration fees and that. So that alone is pretty amazing so the fact it works at all and it’s free, is pretty good.

Adam Smith:

I’d agree, that’s put me off attending a couple of things later in the year I have to say, the fact that they still charge, I don’t know…

Adam Smith:

I mean clearly they’ve got overheads to still cover, but to pay the same amount of money when there isn’t a venue and things like that, does feel tricky. What about you Courtney, what do you think?

Courtney Kloske:

I’ve really enjoyed it, I feel like I’m getting to see a lot more that what I normally do in person, because we don’t have to run across the whole convention centre and you can just watch that one clip and then automatically go to the next talk. You don’t have to the like, “Oh I’m stuck in this room for the full four sessions.” You can switch between different talks and we have a whole month or two, depending on if you’re an ISTAART member or not, to go back and watch more videos and check on the posters, so I think that as much as I wish I was in Amsterdam this is a nice second.

Adam Smith:

It is, there’s that kind of balance. Whilst what you’ve lost in networking, we have gained in better use of time. The ability to see so many things in one day is really awesome. We will be interested to see if they survey afterwards the people living with dementia and carers and things which of course have been enabled to participate this year, which this is one conference that doesn’t really have a high attendance, quite understandably so. I think it’s quite heavy on the science, that isn’t to say that people with dementia aren’t welcomed or their options aren’t welcomed, but it is a tricky one this one and I can understand why they don’t encourage that.

Adam Smith:

It’ll be interesting to see afterwards how many actually come back now, and say, “Yeah, do you know what? That’s one conference, we’re not so bothered for that.” Or whether their feedback is, “Yeah we welcomed the opportunity to see the people behind the research.” What about you, James? Are you loving it?

Dr James Quinn:

Yeah, I’ve been enjoying it. It was good. My dad was able to come, and couldn’t work out how to comment on my poster, but he sent me a message on WhatsApp with his questions, so I was able to write that on the poster. And I think it’s things like that which are really, really good and I think it does make it a lot more accessible. And it would be interesting to see, next year, if the whole COVID situation is calmer, whether they will stick to a virtual format or whether it will be a local format instead of being a full-blown conference. It would just be super interesting to see where conferences go in the future. And I’ve been really impressed, and the technical support have been amazing.

Dr James Quinn:

Like, my poster wasn’t online when I went on Monday morning, and within 10 minutes I emailed them and they’d put it up. So I think yeah, there’s been a few issues and it’s taken a bit of time but it’s to be expected, and the fact you can go back and look at all of them on demand. And I’m also interested to see how early career researchers have managed it with respect to being in a lab and things, because for me a conference you need to fully get involved and you go to AICs and five or six days at a conference you get really involved and have all of those opportunities to network.

Dr James Quinn:

So, it’ll be interesting, I don’t know if Dementia Research want to do anything around that, it would be quite interesting to get some kind of feedback, because I think it’s quite an important thing, because I put a Twitter poll out and it was like 67% of people have been going to virtual conferences have been going into the lab. So I have taken two or three days off to focus on conference, but then I’m going to go back in so it’d be interesting to see how it changes, what’s the word I’m looking for? How people focus on things, and how work gets in the way and all of these kinds of things.

Adam Smith:

Yeah, I think I agree. Understanding, retrospectively, whether people took specific time out to participate in the conference or just squeezed it in alongside other work and what they’re PIs or bosses, how they expected you to engage with the conference as well.

Adam Smith:

It has been tricky because it’s on different time zones, but I think the Alzheimer’s Association have done an amazing job, the people behind it, the IT company, as you’ve said they’ve been super timely to respond to things. I think the whole conference is no harder to navigate than the really life conference, we’re all getting slightly fewer steps but we’re getting more talks in. I’ve got better coffee at home definitely, than any conference venue I’ve ever been to at an Alzheimer’s Association event, so I’m pleased. I think it really is great. And we were talking about this before as well, just as my team, about the future.

Adam Smith:

And you could see how there is a place for this, irrespective of whether we’re clear for big international conferences next year or not, giving people the opportunity to participate in this way, in addition to participating in a physical conference would potentially help a lot of people from lower, middle income countries that struggle financially to attend. Or just can’t take the time out to go swanning off to Boston for a week, but would still like to participate in the conference. So whether they can do, it’s a lot more work I imagine. But whether they can do both at the same time, potentially in the future. Or even do something like, we were talking about this before, like the Olympics do, like the AAICs in the US one year and then elsewhere in the world. Maybe they put in a third year rotation, where every third year is a virtual one.

Rory Boyle:

Yeah, that would be really nice. Yeah.

Adam Smith:

I think what has, I don’t know again because I’m not behind the stats. I think this was a really fascinating opportunity, and I tweeted about this as well. For people from other diseases to come and see what’s going on in dementia. We talk about this all so often, how heart disease researchers and cancer and people working in diabetes and things like this. Could learn from each other, if only they’d go to each other’s conferences. But nobody’s got the money or time to go to a conference that’s not relevant to you.

Adam Smith:

It would be really great if there are some researchers working in other diseases at the moment that came along to this conference to inspire their own working and get some new ideas, maybe. It would be brilliant to see that. This is all we’ve got time for, thank you ever so much for everybody to attend. I wish we were now going off to a bar to enjoy a few drinks, but I’m sure we can all do that in our own kitchens. Thank you very much Courtney, Rory and James, for joining us today.

Rory Boyle:

Thank you Adam.

Adam Smith:

And we have profiles on all of today’s panellists on our website, including details of how you can find them on Twitter. Please do go look at their posters, go look at their talks. Follow them on Twitter, and please do follow up on the conversation we’ve had today with them offline.

Adam Smith:

You can please like, subscribe and review our podcast through the website, iTunes, Spotify, [inaudible 00:55:32]. Everywhere where you find your podcasts, just search for Dementia Researcher. We’ll be back tomorrow with Dr. Anna Volkmer, Daniella Wilson, and Dr. Leonardus [inaudible 00:55:44] to talk about day three. And also as well, I should say, you can ask Alexa now and she’ll find the podcast. So if you just say, “Alexa play the Dementia Researcher Podcast.” It will. Thank you very much everybody, have a good evening.

Voice Over:

Brought to you by DementiaResearcher.NIHR.ac.uk, in association with Alzheimer’s Research UK and Alzheimer’s Society, supporting early career dementia researchers across the world.

END


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