- DEMENTIA RESEARCHER - https://www.dementiaresearcher.nihr.ac.uk -

Podcast – AAIC 2019 Day Three

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

Day Three – Adam Smith [1] is joined by Robin Brisbourne from Alzheimer’s Research UK, Dr Lucy Stirland [2] from The University of Edinburgh and Thomas Doherty [3] from Syneos Health.

Check back at this time tomorrow for news from day four, and checkout the twitter feed with #AAIC19 to find more [4].


Click here to read a full transcript of this podcast

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, and welcome to day three of our AAIC podcast recordings. I’m Adam Smith and all week I’m here in Los Angeles making these podcasts for the NIHR Dementia Researcher Website. We have new panellists each day discussing their presentations, highlights from the day, and what they’ve seen and heard that has interested them. And I’m looking around at my new panel today. We’re joined by Dr. Lucy Stirland from the University of Edinburgh. We’ve got Robin Brisbourne from Alzheimer’s Research UK, and Thomas. Is it all right to call you Tom?

Thomas Doherty:

Tom, yeah.

Adam Smith:

Tom Doherty from Syneos Health?

Thomas Doherty:

Syneos Health.

Adam Smith:

Syneos Health. Thank you for very much for joining us.

Thomas Doherty:

You’re very welcome.

Dr Lucy Stirland:

Absolutely.

Adam Smith:

So, first of all, maybe we could start with a little bit of a round table to do some introductions, Robin, if maybe you’d like to go first?

Robin Brisbourne:

Sure. So, I’m Robin. I’m the Science Communications Manager at Alzheimer’s Research UK. So we deal with research press, so that’s why we’re here at the conference, to send out AI UK comments on the breaking new stories. We’re also trying to engage a research audience with the work of AI UK, and to provide content for our various social media and digital channels while we’re out here.

Adam Smith:

Brilliant. Thanks, Robin, and Lucy?

Dr Lucy Stirland:

Hi. I’m Lucy Stirland. I’m an old-age psychiatry trainee up in Edinburgh, and I’m doing a PhD at the moment, so taking time out of my training to do a PhD on epidemiology. I’m looking at links between physical multi-mobilities, so having multiple chronic conditions, taking multiple medications, and links with various brain and mental health outcomes.

Adam Smith:

Thank you very much. Actually, you’re having advanced side of your biography, for both of you and Tom. I thought you both had really quite interesting career paths compared to many of our other early career researchers that join us, because you have come at this from clinical first, really.

Dr Lucy Stirland:

That’s right, yeah.

Adam Smith:

Aren’t you supposed to wait until you’re finished before you go into researching?

Dr Lucy Stirland:

Well-

Adam Smith:

Did you get bored in the middle?

Dr Lucy Stirland:

So the best time, because also I’m halfway through my higher training in old-age psychiatry. And the way that the funding programs work is they want to train you when you’re still within the training, to do the research.

Adam Smith:

So it’s a clinical research?

Dr Lucy Stirland:

Yeah.

Adam Smith:

Oh, okay.

Dr Lucy Stirland:

It’s a clinical research fellowship.

Adam Smith:

Fantastic. And how about you, Tom?

Thomas Doherty:

So my name is Tom Doherty. I’m part of the cognition team on the Eisai Mission AD BACE inhibitor trials. We are trying to find a therapeutic that actually works. My role is essentially finding the right people to come into the trial. So, me and my team also look at cognitive endpoints for screening and also looking at how we can better pre-screen the subjects through conversations and dialogue with PIs and their sponsors.

Adam Smith:

Brilliant. And you’re at early career research yourself?

Thomas Doherty:

Yeah, exactly. So I will stay on the side, just doing a casual part-time PhD as well, just because I didn’t think it was hard enough there.

Adam Smith:

Now that’s a back to front look because you’re supposed to go to industry after your PhD.

Thomas Doherty:

Yeah. That was the first bit of advice I was given.

Adam Smith:

You sold out early.

Thomas Doherty:

Yeah. I stored the money, enough for it.

Adam Smith:

Hold on. Sure, I’m not allowed to say something that way. Moving to industry is a very interesting career path, and I think it should be a topic for our podcast in the future.

Thomas Doherty:

Well, yeah. It’s certainly different academia, that is for sure.

Adam Smith:

In what way?

Thomas Doherty:

It is a lot faster paced. You’re expected to do a lot more a lot quicker. I have always had a soul passion for actually looking at the drugs that are used in certain therapeutic areas, so I kind of had a bit of wit, background into getting into it. So I started off, I did a Masters up in Sheffield Hallam in cognitive neuroscience. I ended up publishing on cognition on a new endpoint. I then ended up working for a cognition company, in the academic department, then moved into their pharma team, where I found my love for Alzheimer’s an interest and so I went from there.

Adam Smith:

Brilliant. Well, thank you very much, everybody, and thank you for taking time out and skipping the last session to join us. And I’m assuming you told your kin to get off and get to that session. Yesterday’s podcast ran about 40 minutes so apologies for anybody, we may tired yesterday. But today, honestly, we’re going to keep to time. It will be there on the ball. I was planning to ask all of you if you have been in any VCR sessions and then chatting on the way here. I know none of you have.

Thomas Doherty:

[inaudible 00:04:37].

Adam Smith:

Do you know I still feel the need to point this out because I think one of the things we have seen from the Alzheimer’s Association is they have been really fantastic at trying to support more early career researchers. You can see that throughout the event, both in terms of these lunchtime out sessions, where they bring senior people in, for early career researchers to ask questions of. There is lots of extra seminars on, just for early career researchers. The room we’re sat in now, is used for training sessions on a lunchtime. Lucy, you have benefited, you said…

Dr Lucy Stirland:

Yeah, there were free head-shots for students going on today, so I thought why not-

Adam Smith:

There you go.

Dr Lucy Stirland:

Get a new head-shot.

Adam Smith:

Free head-shots. There is a room, just for early career researchers where I believe the snacks are free.

Dr Lucy Stirland:

Yes, free snacks and coffee.

Adam Smith:

And if you it turn out to be in it, like any of the other academics I deal with, that will be a head-shot for the next 30 years. [crosstalk 00:05:25].

Robin Brisbourne:

Even when you’re 60.

Dr Lucy Stirland:

Have some work done.

Adam Smith:

And we know of… I think we’ve got Olsson Smeil, joining us tomorrow who has been a previous ISTAART and conference volunteer. I know he’s a very big supporter of that and encourages other people to do the same. Honestly, I think there is lots here for everybody. And they were talking today, but next year’s conference, of course, is going to be in Amsterdam, which I think for those 50% of our listeners that are in the UK, hopefully, that will make this conference far more accessible and affordable for everybody to go to. When it’s just across in Europe.

Robin Brisbourne:

And do you know what proportion of attendees or speakers are actually early career researchers?

Adam Smith:

I don’t but-

Robin Brisbourne:

Did they tell you about that?

Adam Smith:

But I don’t they have, but with having looked around, you can’t help but notice that, certainly, I feel quite old and I’m in my 40’s. There’s a lot of younger people here, aren’t there?

Robin Brisbourne:

I know, this is the first one I have been to where it has actually felt I wasn’t in the minority by being under fortyish, or something there.

Adam Smith:

We have talked about this a couple of times now, and I think I started to come to this conference about six or seven years ago, and then you could say it was a lot of older men, particularly. And I think, in that time, we have seen now, we’re talking about yesterday, half of the people here, more than half the people here win.

Robin Brisbourne:

It’s my second year in a row.

Adam Smith:

I really will be interested in seeing that breakdown of how many people are early 20’s to early 30’s, 40’s, 50’s. Anyway, thank you very much again for joining us, and really do consider this, if you’re an early career researcher. I say, well, let’s just move through this and talk about who… I was going to say hands up if you have been delivering a presentation. Yep, everybody’s got hands up. Lucy, have you been doing a talk or post anything?

Dr Lucy Stirland:

I’m giving a talk tomorrow, on Wednesday.

Adam Smith:

Oh, fantastic. Given that nobody will be hearing this until tomorrow, do you want to tell us what you’re presenting about?

Robin Brisbourne:

Sneak peek.

Dr Lucy Stirland:

Yes, sneak peek of what I’ll present. I have got a 15-minute slot in an epidemiology session at the end of the day tomorrow. I’m not sure how many people will be coming, but I don’t think it will be very big. My work…

Adam Smith:

You will be surprised. Everybody seems to be happy to stay until the end session, apart from on Sunday when they’re welcoming you.

Dr Lucy Stirland:

So my work is looking at people with multiple chronic conditions and amyloid on CSF. So I have used data from EPAD, which is the European Prevention of Alzheimer’s Dementia consortium and it’s the first 500 people’s data. So I have just done a cross-sectional analysis and looking at having multiple chronic conditions and CSF amyloid, and we found surprising results. So we know the end people with dementia, who have clinical dementia, if you look at population studies, the vast majority of those people will have more than two other conditions. So 82% of people with dementia have at least two other conditions. So we’re expecting that amyloid, probably be related to having multiple conditions. We expect it probably would be. But we actually found the opposite, so the more chronic conditions you had, the less likely you were to be amyloid positive and CSF.

Adam Smith:

So were there others, of pathologies involved in the opposite?

Dr Lucy Stirland:

So that’s what we suspect, but-

Adam Smith:

So other biomarker pathologies, so it’s that one.

Dr Lucy Stirland:

Yes, or it could be vascular. The limitations of doing cross-sectional research on this is just very much we can only say what we found and we can’t infer causality or anything else, but it did make us think, maybe multiple morbidity and amyloid, maybe amyloid doesn’t own that pathway between multiple morbidity and dementia and maybe the amyloid, we don’t know, is related to Alzheimer’s disease. But maybe the development into clinical dementia has more to do with other things, multiple morbidity, other pathologies. So interesting stuff.

Adam Smith:

It is.

Robin Brisbourne:

We should check out.

Adam Smith:

I’d like to think of what the implications of that are.

Dr Lucy Stirland:

Well, we can’t really say-

Dr Lucy Stirland:

We advise you to get as many conditions as you can to prevent [inaudible 00:09:28] positive.

Adam Smith:

Those are the conditions likely to have kind of had caused a low mortality rate. So if they’ve managed to live as long with the diabetes or the other conditions that they have-

Dr Lucy Stirland:

Yeah, it could be. And EPAD’s healthy volunteers… There’s always that difficulty that you’ve got people who are… People are excluded from the study if they had a really major physical health problem or any contraindication to having a lumbar puncture. So you end up with healthy volunteers and they are relatively young as well. The mean age is 66. So for people with dementia it’s pretty young.

Adam Smith:

So what are the most common kind of morbidity for people with dementia, because like diabetes and hearing loss.

Dr Lucy Stirland:

So in this cohort, the most common was hypertension and followed by cancers, but they’re probably historical, thyroid, depression, diabetes. But yes, and in the general population it’s often vascular things. So you wonder how much of it is to do with multiple pathologies.

Robin Brisbourne:

So that is interesting.

Adam Smith:

I was just going to say on that note, do you think that potentially looking at the sort of ATN framework that a lot of the newer generation marketers may infer a bit more information on the cohort?

Dr Lucy Stirland:

Yeah. So one of the previous studies that we… So that the work that I’m doing is in press as a paper as well. And one of the previous studies that we cited found that amyloid on new imaging and multiple morbidity would be associated if there was a Neurodegeneration marker as well. So it didn’t seem to be associated on its own, but when you start adding in other things, yes.

Adam Smith:

And I’m a participant in prevent… So maybe I should vert. Has Prevent been around long enough, that you’ve seen people who went into it without memory problems, now having come for their follow-ups and having got one in the meantime?

Dr Lucy Stirland:

I don’t think that Prevent follow-up data are out yet. I don’t-

Thomas Doherty:

[crosstalk 00:11:25].

Adam Smith:

Is its two-year follow-up’s? It’s every two years, isn’t it?

Dr Lucy Stirland:

Yeah.

Adam Smith:

So I guess-

Dr Lucy Stirland:

I’ve only seen the date from the first one.

Adam Smith:

I’ve only had one follow-up and I think I was in the first year. So I guess, yes, but still early days.

Dr Lucy Stirland:

The Prevent follow-up date, is coming out later this year.

Adam Smith:

Fantastic. What about you? Tom you’ve been presenting as well.

Thomas Doherty:

Yes I had a poster on Sunday morning, so straight off right out the blockchain, the conference. My sort of research was based around a trial that I’m working on, so we had about 11,000 subjects, so quite a rich data set. And we were sort of interested in what the cognitive profile across the regions were. So it was literally name a country we were… We have a site there. So what we found actually is in North America, essentially West, the Western world. As you would expect with the prodromal sort of MCI population. The memory impairment on the episodic memory tasks that we used was a lot less impaired compared to the rest of the world significantly. So when we looked at the MMSE, the South America region was essentially the worst in ISLT, but they had the highest mean distributed MMSE score.

Thomas Doherty:

So a bit of a dichotomy. We’re not sure why that may be, but an interesting finding nonetheless. And then when we went to the CDR, so the primary endpoint in most clinical trials now. Japan and APAC, had the sort of lowest summit boxes which we think is indicating sort of cultural biases towards sort of that region in terms of subjects, not some of my subjects, but study partners tend to, it’s a very different mindset in terms of a lot of families feel the need to look after their own and not put a lot of pressure on a doctor. They think that they can deal with it a lot of the time. So they tend to, we think underestimate the impairment somewhat. Just to add to, this is not the recruited part-

Thomas Doherty:

This is not the enrolled population. This is just the screen population. So this includes screen fails and randomised patients. Although there was… We speaking to comments, it’s about the epidemiology, presentation also talked about American Asian communities having the lowest incident rate wasn’t it growing by quite a significant proportion.

Adam Smith:

That’s fantastic. Did you get a lot of interest? Was this-

Thomas Doherty:

Well, I had more interested on people asking me about the state of the base inhibitor fields. And why we’re still going and what our drugs different essentially. So that was quite interesting actually. It’s quite fun to essentially to battle away the questions with some science.

Adam Smith:

Well actually, what’s the state of the base inhibitor theory?

Thomas Doherty:

You want me to go there a little?

Adam Smith:

Yeah.

Thomas Doherty:

So for the listeners, so for those not familiar with sort of clinical trials and AD. Beta-secretase, is essentially one of the cleavage enzymes that we think is, plays a causal role in the accumulation of amyloid. So this compounds, this class of compounds essentially inhibit this cleavage. And essentially the premise of the hypothesis is it arrests the build-up of amyloid to a degree. So in terms of the other compounds that have failed, so I think there were six or seven compounds that have gone into phase three over the past four or five years. The one I’m working on, is the only one left. They have all stopped for different reasons, which I think is really important.

Thomas Doherty:

There’s a lot of different safety profiles, but across all of them. Needless to say, we have a completely clear safety profile. There is no worsening of cognition, which has been found on two of the other base inhibitors. We haven’t got any liver toxicity, in terms of skin rash or lymphocytes opinion. And there were two others that were stopped for futility early on. So we haven’t seen this. We’re basing the fact that they’re slightly different upon a number of factors. A lot of them hammer the target, so they reduce CSFA beta by up to 90%, whereas ours is a lot lower. And also the selectivity for base one and base two. So base two is essentially a lot of off target side effect profiles that we’ve seen with other compounds, which we haven’t seen with ours. The selectivity is another issue though, but we’ll be continuing until it’s finished. We’ve just been put into a three prevention trial in the US, to replace the other ones that have failed. So that’s always a positive sign, when the NIH is funding it, or… I can’t remember the acronym in the US but is similar, I think.

Adam Smith:

Put it on the track as well for being fast-tracked if-

Thomas Doherty:

I think so. Yeah. But that’s in preclinical, whereas the prodromal trials that I’m working on, they’re still being funded solely by Hayes and Biogen. But that’s as brief as I can be, I think.

Adam Smith:

You know what? I think that’s interesting. I mean, obviously most of our listeners are really good researchers, but I think we know that they keep an eye on the news even if this isn’t their field, because we do have everybody that works from care in dementia and these are questions that they’re, dealing with, with people living with dementia every day. So being able to answer questions about where we’re at with drug trials and things are interesting.

Thomas Doherty:

It’s still worth putting them into a drug trial.

Adam Smith:

And you can do that via joint dementia research in the UK-

Thomas Doherty:

[crosstalk 00:17:12].

Adam Smith:

Or in trauma actually in the US or, or the various other cohorts around the world. Thank you very much Tom. So the morning sessions, I didn’t make as I was busy doing emails and getting this podcast out there. But this morning was emerging concepts and I think there was a session on infection and something on early detection. So Robin you went to the infection discussion.

Robin Brisbourne:

I did. I went to the infection discussion and it was really interesting. I always see this as quite a contentious topic in the dementia research community. So I work in the press team at Alzheimer’s Research UK and every so often the press will get wind of this sort of issue. And then we are tasked with trying to say something sensible about it. And the same people appear commenting on these stories and people do seem to have some quite invested views on this topic. But it was very civil debate, very good natured. And I find that I believe whoever the last person wants to tell me something. It’s all sounds very plausible.

Robin Brisbourne:

So what are the two sides of the argument? Well, essentially that infections, whether they be bacterial, viral or fungal infections, somehow seed amyloid deposition in the brain. And there’s this idea that a beta is actually a mechanism, not as much as this functionless by-product of misprocessing, but it actually has a function in terms of entrapping infections in the brain. And there’s some pretty, no… Pretty good associative data, now I think where, things like the herpes virus is colocalized with amyloid deposition in the brain. So I think there is some quite strong circumstantial evidence, but there are many different reasons why that might be the case. And those alternative views were put forward by the opposing side.

Adam Smith:

Did anyone say anything about the gum disease hypothesis?

Robin Brisbourne:

Oh yeah.

Adam Smith:

Or context on-

Robin Brisbourne:

Gingivitis?

Adam Smith:

Yeah.

Robin Brisbourne:

It actually mostly focused on herpes, but there was some mention of gum disease in the session. And I understand that this is more to come on that tomorrow, posted on that-

Adam Smith:

Special insider.

Robin Brisbourne:

Tomorrow and that would be awful, 20 years on line, you just find gum disease is the-

Adam Smith:

[inaudible 00:19:47].

Robin Brisbourne:

Main cause of Alzheimer’s. Absolutely. I feel that-

Thomas Doherty:

When was my told.

Robin Brisbourne:

I’m sounding ridiculous, but-

Adam Smith:

Stranger things have happened. That sounds good. Thanks Robyn. Tom, what did you go through this morning?

Thomas Doherty:

Yeah, sure. So I went to a session on early detection and diagnosis. So it was looking at sort of more preclinical prodromal endpoints in cognition. So there’s a really interesting talk by Phillip Shelton’s about one of the cohorts they have in Amsterdam, looking at the ATN framework, but looking from a clinical care points of view. So they had about 700 subjects in total, that he presented data on and of those 18% had a subjective cognitive decline. No sorry, they all had some form of subjective cognitive decline, but 18% of them had AD positive biomarkers, so A+. And then TRN regardless of wherever they were. And what he showed as well was in terms of all comers to the memory clinic, they are great cost to them. And to be quite commended, I think that they essentially put everyone through a PET scan, and CSF.

Thomas Doherty:

And of all comers to the memory clinic, 49% were amyloid positive. But interestingly, that still means the majority of the people coming do not have Alzheimer’s pathology. So, kind of tying in with what you were saying Lucy, about sort of comorbidities, just there is just such a wide spectrum, if you look in the sort of clinical community care centres.

Adam Smith:

Fantastic. Anybody got any questions on that one? Come on everybody, come on, think of a question. There was stone faces off at the end. We talked about this yesterday. Really don’t be shy. Fantastic.

Robin Brisbourne:

Exactly. Did you come to our conference, Adam? Did you come to our early detection debate at our conference, quite similar session.

Adam Smith:

I don’t think I did. I didn’t buy a ticket.

Robin Brisbourne:

Or we didn’t let you in?

Adam Smith:

No, I was allowed to come, but I was only allowed to sit outside and talk about Dementia Research [inaudible 00:22:01].

Robin Brisbourne:

Oh, right, I think as you kind of mentioned because-

Adam Smith:

I didn’t have the right colour of your lanyard.

Thomas Doherty:

Yes, yes. Security would have turned you away.

Robin Brisbourne:

Just go with that one. Put me on the spot there. We can move on to that. Well I did sit through a podcast and we’re going to talk about my career next one, but don’t question me on that one either.

Adam Smith:

But there was questions that the audience raised about the utility of early detection when we don’t have… Until your work is done on your base inhibitor, we don’t have effective treatments. Did that topic come up at all during the discussion?

Thomas Doherty:

Not actually. It is a fair point to be honest, and what is the point in telling people that they have an incurable disease.

Adam Smith:

Well, we talked about it yesterday. So there’s the potential for the combinations of biomarkers to then allow you to predict earlier, which is fantastic because then it generates a group of people for you to maybe involve in your research studies or that you can target more or that you can follow through. But in terms of until you’ve got something to offer those people by way of a treatment it’s great, but that work then has to run in parallel with the efforts to prevent or treat.

Thomas Doherty:

Yeah, definitely. And I think there’s definitely a quite a wide breadth of options for people. Even if they do have an early diagnosis, there’s plenty out there in the scientific community for them to be getting involved in that can potentially help.

Robin Brisbourne:

And also in here and now take more of an interest in what you can do to slow cognitive decline through lifestyle changes [inaudible 00:23:34] immediate-

Thomas Doherty:

Definitely.

Adam Smith:

So I was talking to somebody earlier who was doing some… They’d done some research in Canada, looking at exercise programs in rural communities in Canada and they were presenting to suggest that improving physical activity post diagnosis actually seemed to give you a better quality of life and potentially delay the onset of the symptom.

Robin Brisbourne:

What’s the tagline, is what’s good for your heart. It’s good for your brain, essentially.

Adam Smith:

You know what I mean? These are the same things we should all be doing now, sat around the table to avoid heart disease and diabetes and everything else. Anyway. So let’s move on to the two sessions that were in the big room, Which was Shane Liddelow from NYU was collecting the grin. Oh, here we go. Inge Grundke-Iqbal Award, for that was talking about his labs work on microglia and astrocytes, which was fascinating. I mean, he was engaging wasn’t he? I think he’s been everybody’s… I’ve read this on Twitter, he was everybody’s favourite speaker today.

Robin Brisbourne:

That’s how you hold a room.

Adam Smith:

How well do you reckon his?

Thomas Doherty:

He must be early 40s, late 30s.

Robin Brisbourne:

Yeah, 30s, Australian, quite dynamic, quite… Did things the right width, thanked all his team right at the start, not at the end.

Thomas Doherty:

Very self-deprecating as well, which he was always funny in a big audience, I think.

Adam Smith:

Yeah, he was really good. So he didn’t present a specific thing, that because I think he was accepting his award. He was presenting more about the work that they’ve been doing, but he did come on at the end to say what he thought the questions were that they could be answering through astrocytes.

Robin Brisbourne:

A lot of I don’t knows.

Adam Smith:

So who wants to talk about his talk first? Anybody?

Thomas Doherty:

I mean, I’m not a microglia expert. I don’t think the right teams or seminars but that’s-

Adam Smith:

Just in case, because knowing that not many of our podcast listeners might necessarily also know what microglia is, even though we did do a podcast on microglia a few weeks ago, I did take a little photograph of somebody posted that, it explains it. So unless somebody wants to have a go at explaining what microglia are. God, we’re so thick aren’t we? I can read out what-

Thomas Doherty:

It’s just the immune response in your brain essentially. There are cells that support homeostasis of neurons. I think what… God, I’ve forgotten his name. Who was the guy? Liddelow?

Robin Brisbourne:

Yeah, Shane.

Thomas Doherty:

Shane Liddelow.

Thomas Doherty:

Liddelow, yes. And he was talking primarily about astrocytes for sure. It’s another type of immune cells in the brain. And how that interacted with the pathology of Alzheimer’s, I think. Is kind of the rough idea. But I see you’ve got your phone up.

Adam Smith:

No, it’s all right. Because I might struggle with some of the pronunciations as well.

Thomas Doherty:

But the idea essentially is that they react to Alzheimer’s brain changes and that can actually contribute to take and speed up the pathological decline, I think.

Adam Smith:

So really engaging speaker, held the room, presented very much like a TEDx. This was-

Thomas Doherty:

Very much though.

Adam Smith:

This was like a Ted talk.

Thomas Doherty:

The slides went down and just kept going, couldn’t stop him.

Adam Smith:

That’s right. And the slides were interesting. They weren’t just bullet points or graphs you couldn’t read or pictures that well, highlights or something.

Thomas Doherty:

Kind of academic scene to choose to use.

Adam Smith:

So he ended by highlighting what he thought was some unanswered questions. And I do you know what though, having listened to that microglia podcast that I was there while it was being recorded and having… Because microglia was a big topic at your conference, Robin AI UK this year as well.

Robin Brisbourne:

How would you know, you weren’t let him.

Adam Smith:

But I talked to… I know that there are people at Edinburgh particularly are looking at microglia through the DRI, they’re looking at that. And I get a sense of that there are a lot of questions in this. People are convinced that this is particularly important, but there are a lot of questions and that’s what Shane highlighted. So his questions that he highlighted were what is a reactive astrocytes and that they’re still finding out, but they know that there are at least two different types.

Adam Smith:

What are the molecular triggers or functional consequences, what features distinguish a reactive astrocyte from a non-reactive, and they think they’ve got a good idea, but they’re hampered by not having very good resting versus reactive astrocyte cultures. Cultures was important as well. Then he talked, at the start about the importance of…

Thomas Doherty:

He seems like he spent a number of years trying to perfect that and actually going back through the literature, which is kind of quite a key point I think, I took away from that, was he was still quoting research from the ’70s in his plenary. Which kind of speaks to sort of…

Robin Brisbourne:

That willingness to combat.

Thomas Doherty:

The long to longevity. And actually looking through the literature even at his sort of seniority.

Adam Smith:

Actually it’s funny enough when we were talking about collaborations were sort of talking to somebody about this yesterday, wouldn’t it be great if you just picked a third of the people that from this conference and sent them off to an entirely different disease area conference, just for a year. Does half a year of going to conferences from completely different disease areas just to maybe inspire you or start to make some of those connections that we otherwise don’t. Instead of going to a conference that’s full of people like you researching things that you’re looking at. Duplicating effort when you could go off and just spread your way.

Robin Brisbourne:

You’re going to fund it, are you?

Adam Smith:

Maybe ARUK would like to… Either think about that.

Robin Brisbourne:

We wouldn’t like to make any commitments right now, but we do have interdisciplinary research grants to try and address this very issue. Get people from outside the field working on dementia, more plugs to follow that.

Adam Smith:

And I think that’s a really great idea. And you lead that. I think nobody else is doing that at the moment, are they?

Robin Brisbourne:

I’m not sure, but we certainly do.

Adam Smith:

I had one more question at the end. Is Astroglioses…

Robin Brisbourne:

Gliosis.

Thomas Doherty:

Gliosis.

Adam Smith:

Astrogliosis an all on non-process or a graduated one. And is that a good thing or a bad thing? He also ended by giving some advice, didn’t he? Just to early career researchers and other PIs, which was a bit of a takeaway.

Robin Brisbourne:

It was the biggest cheer of the week, I think from that-

Thomas Doherty:

Wasn’t it?

Robin Brisbourne:

He was very uplifting actually.

Adam Smith:

I think he’ll be a person to watch in future. And I’ve made a note, his name on Twitter is Liddelow@ L-I-D-D-E-L-O-W-S-A. So @LiddelowSA. I hope he appreciates the big plug we’ve just given him, but well done. If you do happen to be listening, Shane, well done, congratulations on your award and we really enjoyed your talk. The next talk was Rachel Whitmer from UC Davis School of Medicine talking about epidemiology. And I’m going to come to you now, Lucy. In fact, can I just sit-

Dr Lucy Stirland:

That was well.

Adam Smith:

Lucy over to you. Tell us about…

Dr Lucy Stirland:

So Rachel Whitmer, the title of her talk was The Epidemiology of Diversity and Dementia. And she was… I think is can, quite good for plenary. It was just giving a summary of what is out there and what the important issues are and diversity rather than presenting brand new findings on a specific topic. And I thought she did a great job of making it accessible, but then I’m an epidemiologist, so it’s accessible to me. So she’s part of a team at UC Davis that focus on trying to reduce inequities in brain ageing research. So and looking at making sure that demographics are represented in different studies.

Dr Lucy Stirland:

And I think a lot of the main areas where she was talking about was ethnicity and race. And really making sure that in their studies, they focus on adjusting for that or making sure that people from different races and ethnicity are included. Because quite often, White Caucasian is the default and things are, as you said earlier the rates of dementia are much lower in what they call Asian-Americans, which I think we would probably call Southeast Asians and much higher in African-Americans. But is that to do with where they’ve been picked up and the trajectory? Is it to do with other issues like early life factors. So she had lots of compelling things to say about the powers of inclusion.

Thomas Doherty:

I think when you get to sort of the early age for Alzheimer’s vasectomy, a very family orientated approach to whether you’re going to seek advice or not per se. But you weren’t there.

Adam Smith:

I mean she wasn’t presenting any particular research, was she?

Dr Lucy Stirland:

Yeah.

Adam Smith:

It was more about the field at the moment, although I picked up on four particular points she made, which was African-Americans at a higher rate of dementia but no fast declined. And could that be explained through the recruitment or study design or is it the disease? That 190,000 lives of Americans could be saved if they had the same dementia rates just Asian-Americans. Slightly adding up the numbers there, but that is to suggest, then I guess the Asian Americans had a lower rates. Although again, this is epidemiology, that could be cause, they’re not regular diagnosing in that community. You mentioned before that they’re quite good at hiding the symptoms-

Thomas Doherty:

Yeah, they’re not going to approach the doctor.

Adam Smith:

And covering, family members covering for each other. I suppose there’s lots of explanations. And my colleagues hate me for this because I’m really good at picking up on that, “Yes. But what about this? What about that?” I’m awful for that. What else did she say, that 9.6 times more common of a… You were 9.6 times more likely to develop AD if you were born in a high risk stroke state. By state I assume she means states that have more stroke people, have strokes.

Thomas Doherty:

Not as in a state of stroke.

Adam Smith:

No. The States that have got bad reputations for having stroke, which I guess could be for lots of…

Thomas Doherty:

Dietary reasons, you’ve got to say that.

Adam Smith:

Although even in the UK stroke rates of just for those, because things like we’re better at quickly prescribing, busting drugs and having the centres better located to people responding to these things more. So I don’t know if it classes as a stroke, if you initially report the symptoms but then treat it quickly. I don’t know. One for our NHS colleagues-

Robin Brisbourne:

I should have some liquor because of Lucy, who is an SPR. Are you an SPR?

Dr Lucy Stirland:

Yes. No, I think it would still count as a stroke even if it was caught quickly. But it might be that the long term consequences are better managed so people still have strokes but recover more quickly or-

Adam Smith:

What smoking isn’t it? The stopping smoking has made a massive difference, to smoking cessation rates and there’s probably an ICD-10 code for the start and the end. Anyway, so that was fantastic. She had some takeaways at the end that they were a bit vaguer, I’ve got up here if you, if you didn’t if you didn’t write-

Dr Lucy Stirland:

What I like, the thing she said at the beginning about epidemiology. So she to them-

Adam Smith:

Oh, yes. Go on.

Dr Lucy Stirland:

She had some key messages. I was disappointed she didn’t put the slide up, again at the end, but she thought that life course science was essential. So looking at factors across the life course, not just in later life. And pointed out that understanding brain health is as important as dementia and neurodegeneration. And actually seeing it more about health. She called epidemiology, the basic science of public health, which I quite liked and said it was more than simple counting, which made me feel better about my PhD, which I think is just fancy counting.

Adam Smith:

We expect to see that in a slide from Lucy soon. Brilliant. Thank you very much for talking about those mini sessions. We’re at, we’ve got over half an hour now, so we’ve only got a little bit of time left, but I will go around now and just ask if there’s any other particular talks or presentations you’ve seen today that you wanted to mention. How about you, Robin?

Robin Brisbourne:

Nothing today that really stands out, but I did go to a good one about precision medicine yesterday, I think it was and that really caught my interest. So you can have these metabolic subtype of Alzheimer’s and the inflammation subtype and a depressive subtype. And there might be targeted treatments for those particular subtypes. It’s quite beguiling idea. I don’t know if the science is really there yet, but you can imagine that it could have big implications for treatment. And that’s what James Quinn, for those who listened to Sundays, Mondays, day one’s podcast, James Quinn sort of was having, that’s the area of work where he’s gone off to Harvard to look at that, is precision medicine and tailoring drugs and combinations of drugs to individual people and trailing them for short periods of time and then moving on and in individuals rather than applying this to cohorts or groups. Which is quite an expensive, I guess, long way around going to it.

Adam Smith:

Hey, it’s a good idea. Thanks, Robin. How about you Lucy?

Dr Lucy Stirland:

I actually saw an interesting poster that related to things that were talked about in the epidemiology diversity talk. It was from Kaarin Anstey. So it was, I think a collaboration between Australian and Newcastle researchers, and they’d done a meta-analysis of systematic reviews of risk factors for dementia. And they have these two maps of the world with different colours on, about which areas were underrepresented. And so looking at, even in systematic reviews, which you think are great, we’ve looked at all the all the research that’s out there and synthesized all. Actually if that research only takes place in the UK, Europe, America, they’re still missing out, Asia, Africa was just red on both of the pictures. So there was very little research. And then Australasia as well. So I thought that was really interesting to look. And then they listed each of the risk factors and said these are limitations in the research of each risk factor. Which would be really, really good for directing future research in the area.

Adam Smith:

I don’t know, you can see that. There was just so many posters on there. Honestly, you get your steps in walking up and down the poster boards. There’s over 500 posters each day and trying to find time, I think all you can do is go through the list and make your… Or you whip around with your camera phone, right?

Thomas Doherty:

Yeah, exactly.

Adam Smith:

And take photos. And look at them on the plane on the way home.

Thomas Doherty:

If you ever present, you need to make sure the title is snappy, is presented right, otherwise people would just walk past.

Adam Smith:

And I’m sure lots of our RCL, because we’ve done sessions on talking about poster design before but there’s some YouTube videos going around and I’ve seen on social media of how to design a new style poster where you put your takeaway messaging-

Thomas Doherty:

Straight in the middle.

Adam Smith:

Big fat letters in middle, maybe with a code for scanning and then your notes down the side.

Thomas Doherty:

[crosstalk 00:38:29].

Adam Smith:

There are some people have really used that style here.

Thomas Doherty:

Always emphasise your conclusions. That’s a mind buzzer.

Adam Smith:

Do you know what? They stand out from the crowd and if you can do something that at least let somebody who’s got 20 seconds to read your post to take a message away and snap a picture. That’s a good.

Robin Brisbourne:

I think the biggest innovation in posters is the proliferation of the fabric posts which are usually on the floor next to the poster boards. Not actually on the board.

Thomas Doherty:

So it used to be, go to an airport for a conference like this, you can see all the researchers because they’ve all got big poster Jeeves, but now they just blend into to crowd there.

Robin Brisbourne:

Well and the various insights because the poster boards at this conference are huge. And so you’re told to bring a landscape, but people can bring in people a portrait.

Thomas Doherty:

You can see that people haven’t read the dimensions. It’s overlapping [crosstalk 00:39:09].

Robin Brisbourne:

It’s just little tiny ones that’s fitting in, are the ones that are-

Thomas Doherty:

I think because PowerPoint presentation prints it out as well as [inaudible 00:39:15].

Robin Brisbourne:

And just pinned up. Maybe they lost their poster. It got…

Adam Smith:

What about you Tom? Last but not least, what did you see today.

Thomas Doherty:

It’s all right. It’s another one from this morning session. So there was a really nice presentation I thought on what’s the new sort of cognitive endpoint of King’s college cohort. It’s not very snappy title, I might say, but it’s called the Integrated Cognitive Assessment. Now this is essentially animal semantic recognition task, where you’re displayed an image for a hundred milliseconds followed by a few distractors. Then you’re asked to recall whether you saw an animal or it wasn’t an animal. So this is kind of used really widely, the marker, ADAS-Cog, MMSE as well, I think. Sorry.

Thomas Doherty:

And they’ve essentially shown that this activates the same regions as the early deposition of tau. Now they have, it’s all very preliminary data, but I think it shows real promise in actually looking at an endpoint that might be on PEMA clinical trials that on here again, for the tau antibodies that are coming through. I think it could show some real promise because when they look to the ROC curves or MCI, they combined it with an EEG measure and it was about 0.89, I think it was. So not bad in terms of sort of a first in line diagnostic, I think.

Adam Smith:

And the genetic challenge has been so often, is translating that into something, a tool that can actually be used and which is where we fall down all too often.

Thomas Doherty:

Where exactly. They are actually a company as well. I think it was the professors at Kings, but is part of the ring.

Adam Smith:

So there’ll be a spin out.

Thomas Doherty:

Cognitivity I think is-

Robin Brisbourne:

Cognitivity.

Thomas Doherty:

Cognitivity, there you go.

Adam Smith:

Oh, well that’s good. We see spin-outs come up into something meaningful. It’s just a shame. Be nice. If it wasn’t a spin out then it could be free and it’s more likely to be picked up and adopted then, isn’t it? I think we’re out of our time there. Thank you very much for everybody. If anybody wants to contact you, are you all on social media, on Twitter? So Robin, what’s your Twitter name? Let’s go with you first.

Robin Brisbourne:

@RobinBrisbourne.

Adam Smith:

@RobinBrisbourne. Born as in from the Manor Bourne. B-O-U-R-N-E.

Robin Brisbourne:

Exactly right.

Adam Smith:

Fantastic. Lucy.

Dr Lucy Stirland:

I’m @Stirlandia. S-T-I-R-L-A-N-D-I-A.

Adam Smith:

Fantastic.

Thomas Doherty:

I’m @TomDoherty89. And that’s Doherty without a C.

Adam Smith:

Doherty89. Is that because you were born in 1989?

Thomas Doherty:

It was. Is that depressing a little bit?

Adam Smith:

And @BetterResearch.

Robin Brisbourne:

Obviously, you still got more grey hair in your head.

Adam Smith:

Okay. Thank you very much. I’d like to thank our panellists Robin, Lucy and Tom. Do you all have big plans for this evening? Is there a party going on that I’ve not invited to?

Robin Brisbourne:

There’s a Novartis dinner, but I am going out with a client.

Adam Smith:

Novartis tonight. That sounds like good free food. I could go for some of that.

Robin Brisbourne:

See that.

Adam Smith:

Brilliant. Thanks Robin. We’re going to call a time on that podcast today. Please remember to subscribe and leave a review on our podcast through SoundCloud, iTunes, and Spotify. Tell your friends and colleagues. We’ll be back here tomorrow to record our fourth and final podcast from the AAIC here in Los Angeles. But in the meantime, if you want to see more reflections on the conference and get the views of other people attending, check out their official hashtag, which is AAIC 19. Thank you very much everybody again, and we’ll be back tomorrow.

Dr Lucy Stirland:

Thanks Adam.

Robin Brisbourne:

Thank you very much, cheers.

Voice Over:

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

END


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