Podcast – AAIC 2019 Day One

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. I’m Adam Smith and today I’m hosting this special podcast recording from day one of the Alzheimer’s Association International Conference, which this year is taking place in Los Angeles. So we’ve got a little bit of sun and for the next four days we’re going to be making a podcast recording each day with different people and we’re going to be discussing both their presentations, the main topics of the day and what they’ve seen and heard that’s interested them. So we hope this will be particularly interesting for those that haven’t managed to make it out to the conference, but hopefully there’ll also be something for those that have, because there’s so many things to see here, you couldn’t possibly take in everything. So we hopefully… Even if you’re attending here, please, please have a listen too. So today I’m joined by James Quinn from Boston.

Dr James Quinn:

[inaudible 00:01:00]

Adam Smith:

Some of you’ll remember James recorded with us at the AAIC conference last year when you were in Manchester. So a bit of a big change for James, which we’ll come to in a minute. Sarah Gregory from Edinburgh, who… You’ve had a change of circumstances since last year too, in a good way. And Clare Walton from Alzheimer’s Society who’s also slightly had a change in circumstances this year, to be here. So thank you very much. Welcome to our panellists today. So if we can start by maybe a little round table, if you can introduce yourself and maybe talk a bit about your work. So Sarah, do you want to go first?

Sarah Gregory:

Yep. So I’m Sarah, I’m a part-time study coordinator at the university of Edinburgh coordinating the EPAD and Prevent studies and I have started a PhD at the end of last year, looking at stress in midlife as a risk factor for developing Alzheimer’s disease later. So using Prevent and EPAD data to model risk factors for that at the moment.

Adam Smith:

That’s quite handy, having access to that data-

Sarah Gregory:

Exactly. It’s very handy.

Adam Smith:

Particularly just right there.

Sarah Gregory:

Yeah. Perfect midlife cohorts to be looking at.

Adam Smith:

Is this work you were doing anyway?

Sarah Gregory:

Exactly.

Adam Smith:

And somebody figured, “Hold on a second, I could get a PhD out of my day job.”

Sarah Gregory:

Mm-hmm (affirmative). It all worked perfectly together.

Adam Smith:

Fantastic. Thanks for joining us, Sarah. James?

Dr James Quinn:

Yep. So I’ve recently moved to Massachusetts General Hospital in Boston and we’re looking at ways to basically look at developing new diagnostic biomarkers of Alzheimer’s disease and other forms of dementia and look into mechanisms of disease and also to look at potential therapeutic targets. So similar to the work I was doing during my PhD, but much, much more relevant to patients. So we are seeing patients on a day-to-day basis, well my boss is, and we’re trying to develop personalized medicine-based approaches. So I find it really fascinating over there.

Adam Smith:

That’s really exciting. And does that make you hot property as well? I mean to go from Manchester to Harvard, right? It just must be… You must be… Your mom must be really proud.

Dr James Quinn:

I think my mom is very proud. I had my graduation on Friday and I think it was a… Yeah, I think they really enjoyed that. So… But isn’t it… I don’t know. It’s a really good opportunity and I’m very grateful for that.

Adam Smith:

Fantastic. No, really congratulations.

Dr James Quinn:

Thank you.

Adam Smith:

And it’s nice to see some people going the other way, of course. We hope that we’ll make a good case through this podcast to attract people from the US to want to come and work in the UK as well, in a post-Brexit world. Okay. Thanks very much, James. And Clare?

Dr Clare Walton:

Hi. Yes, I’m Clare Walton. I work at the Alzheimer’s Society. I do research communications. I moved into that after doing a PhD in neuroscience and realising I was much better at talking about science than actually doing it myself. So I help the charity to communicate to generally the LA audience about what stuff we’re funding, but also what’s going on in the world of research. So that’s why I’m here. As Adam just mentioned, I have had a little change in that I just came back from maternity leave-

Adam Smith:

I didn’t mean to out you or anything.

Dr Clare Walton:

… so this is a really great conference for me to see what’s happened in the last year, have things moved on, what’s everyone excited about, what are they talking about, and to take that back to my colleagues.

Adam Smith:

Is this the first time you’ve been away for an extended period of time from your new…

Dr Clare Walton:

It is, yeah.

Adam Smith:

So you’re not-

Dr Clare Walton:

It’s the first time I’ve been away longer than a night.

Adam Smith:

Oh, no. And the time difference makes it quite tricky as well. You can only talk after like 4:00 in the afternoon.

Dr Clare Walton:

Yeah, we’ve got a webcam in her cot and creepily last night I was just watching her sleep, which I know is really weird, but I was jet lagged. I was like, “Oh well, I’ll see what she’s doing.”

Adam Smith:

Stalking, yeah. No, that’s very sweet. And it’s great that you’re here and thank you very much to everybody that’s joined us today. So, you’ve all acclimatised now? You all arrived a few days ago? Nobody just arrived this morning?

Dr Clare Walton:

Last night, I arrived.

Adam Smith:

Last night? Oh, that’s pretty close.

Dr James Quinn:

Yesterday. Yeah, I’m feeling it, definitely.

Sarah Gregory:

Yeah. Friday. I think I arrived Friday. Yeah.

Adam Smith:

Friday? Yeah. So you’ve had the most time to adjust.

Sarah Gregory:

[crosstalk 00:04:49].

Adam Smith:

So yeah, I got here Friday too, just to have that little bit of time to adjust. Fantastic. So we’ve had the opening morning. This was quite an exciting opening morning, as ever. AAICs open with a bit of a bang and today was beatboxers, wasn’t it? Beatboxing-

Dr James Quinn:

Acapella. What more could you want?

Adam Smith:

Tunes that had California and Los Angeles in the title, which… They were really good, weren’t they?

Sarah Gregory:

Yeah. They were great, yeah.

Dr Clare Walton:

The only disappointment was, I really thought they were going to start rapping about amyloid. I was like, “Where are all the science references, and where’s rap?” But didn’t quite get there.

Adam Smith:

They squeezed LA in the front. I have to admit to being a little bit distracted myself because of course the Cricket World Cup Final with England and New Zealand was going on at exactly the same time. So I had my earphones in, if I’m honest.

Sarah Gregory:

I was watching the Wimbledon on my phone. Yeah.

Adam Smith:

You were? Well, the Wimbledon Final dragged on as well, so… And you had the Grand Prix as well. So for those of us or those of our listeners that are UK-based, I have to say it was a little bit exciting and a little bit distracting at the same time.

Adam Smith:

I did manage to see… Is it Harry Johns? Harry Johns’s talk at the start. He gave a really strong message of pointing out that it had been a hard year with the drug trial failures that we’ve seen, but not to be particularly disheartened. Although of course he singled out Biogen as being the one particularly disappointing one. And then of course just last week, the Generation’s Program out of the Banner Institute. And is it Novartis, the partner on that one? That’s also being cancelled now as well, which is… I haven’t understood… I haven’t learned why, yet. Have you had any… Clare, you’re probably the one to know at Society-

Dr Clare Walton:

I’ve only heard through the grapevine that, obviously futility, but actually the people who were on the drug seemed to be declining a little bit worse-

Adam Smith:

Oh no.

Dr Clare Walton:

… in the preliminary analysis. I don’t know. Obviously, there’s been a few base inhibitors that have been terminated, so I don’t know exactly which drug has shown which effects, but that’s kind of the word on the street.

Adam Smith:

So I mean, I only know this through my work on joint dementia research, but that was a population of people that’s been quite a hot area for research recently. Because you had the early study from Janssen looking in that same population of people recently. That stopped as well. And this trial, it’s more annoying than anything else. I suppose Clare, you must feel this being a… Clare? Sorry, Sarah, being a trial coordinator. Because that study has taken at least two, two and a half years to get set up in the UK? All those sites had to become genetic counsellors and there was so much working around the ethics to do with that because of the genetic elements to it. For then it to be… For the UK took so long to get it going, but it’s cancelled then so soon after getting up and running in the UK, must be so frustrating for those sites.

Sarah Gregory:

And for the patients, it is.

Adam Smith:

Yeah, absolutely. I mean, of course.

Sarah Gregory:

I think you have to try and take the good things out of it, that actually you’ve proven that you can do that genetic testing in the UK. You can disclose it to people and it doesn’t cause a lot of trauma to them. So you can take a good learning from it. But yeah, as a coordinator who’s had studies close, it’s telling your participants is terrible, and then you have to kind of re-evaluate what you’re doing.

Adam Smith:

And how you tell them as well. That’s important isn’t it? People finding out from the newspapers, before the trial’s told them, is awful. But I suppose, as you just rightly pointed out, there is some positives to take away from this, which Harry John makes a point of saying that what we learn from failures is just as important as what we learned from successes, and sharing that data was a key theme that he wants to highlight to push back, I think, on so many academics as well, about secrecy and journals, about making sure this data is all public and accessible. He also highlighted the importance of collaborations across diseases, which I know is a… We did a podcast on that. I feel like maybe we were ahead of the curve here. We did a podcast on that a year ago where we had people from Durham and Leeds who are working in heart disease and other areas, collaborating. So, important there.

Adam Smith:

And what else was he making a point about? About being non-political? About not… Obviously, if you’ve got to get your funding in from somewhere, not aligning yourself too much politically and… They got more funding as well, didn’t they?

Sarah Gregory:

Mm-hmm (affirmative).

Adam Smith:

I can’t remember already. Was it 420 or 42 million more every year? Anyway-

Dr Clare Walton:

I missed the details. I think that was right when the cricket finished and I was like, “Oh, there’s just too many things.”

Adam Smith:

Did anybody-

Dr James Quinn:

[inaudible 00:09:20].

Adam Smith:

Yeah. Is there anything… Did I miss anything, do you think, from Harry’s bit there? Then Maria Carrillo did her piece as well. She spent a lot of time talking about that Accelerating Medicines Partnership. I get a sense that you might be more in the know… I’m not going to suddenly put you on the spot, Clare, but we’ve got stuff like that in the UK, haven’t we?

Dr Clare Walton:

Sorry, I can’t remember exactly what… It was an industry partnership?

Adam Smith:

Yeah, it was, and looking for early drug targets and things like that, wasn’t it? That’s okay.

Dr Clare Walton:

I think I missed the details of that one.

Adam Smith:

But I know that she… I mean, obviously, you’d expect that she’d be ahead of the curve, but she pointed out that she thought the strong topics for this week were going to be around DNA damage, stress granules… Stress granules? Sounds like something you can wash away, put in your washing machine. It’s a bit… She did say granules, right?

Dr Clare Walton:

Yeah. I think her point was really acknowledging the failures that we’ve had and saying the community is a bit downhearted at the moment but there’s loads of really emerging areas, and highlighting the ones that the conference has chosen to pick out. I don’t know how they choose some over others, but I’ve not heard about stress granules yet. So I’m really excited to go and find out why they seem to be a hot topic in dementia.

Dr James Quinn:

Yeah, because that was what the DNA damage thing was on, because I went to that this afternoon and that was one of the emerging topics of the conference. So I’m assuming that stress granules and lifestyle and modifiable risk factors are also kind of emerging topics that we’ve got coming up-

Adam Smith:

Yeah, exactly. That was the other point she picked up on.

Dr James Quinn:

… coming out of the conference.

Adam Smith:

So does that mean… Interesting, because you said you were doing patient-specific treatment.

Dr James Quinn:

Mm-hmm (affirmative).

Adam Smith:

Is that targeting specific treatments deficiencies, where looking at stress granules is something you can factor into that?

Dr James Quinn:

Yeah, I think when we talk about precision medicine, we are really trying to look at identifying a different panel of biomarkers. We’re looking at 40, 50 proteins in a patient to see whether treating them with six different drugs… Because there’s a metabolic, there’s a cardiovascular, there’s so many different areas that lead into dementia. Really trying to look at each one of those and seeing, if we treat all of them with lots of different drugs, is that having a bit more of a benefit to a patient? So instead of just testing one Alzheimer’s drug, it’s testing multiple different drugs.

Adam Smith:

And in combination?

Dr James Quinn:

In combinations, yeah, which is a lot easier to do when you use each patient as the control. So my boss, Steven Arnold, he’s doing a presentation on that, Tuesday morning, I think, all about using a patient as their own control. So, putting them on the drug for six weeks, taking them off the drug, putting them on the drug, taking them off, and then using that as kind of its own study. So that’s where you could really look at using multiple drugs.

Dr Clare Walton:

Has that kind of approach been used in other conditions before?

Dr James Quinn:

From what I know, it’s been used quite heavily in cancer research, but less so in the dementia field and it’s something that he and others are really trying to push a lot more. But obviously, a pharma company is not going to want to do that because it’s very expensive. But from a research point of view, it could be really interesting.

Dr Clare Walton:

Yeah, but I’m just thinking, the baseline decline in dementia is so slow that it would be hard to know how much improvement you’re seeing. If you don’t know what the trajectory of that individual was beforehand… It’s probably a little bit different to something like cancer, where we’ve got such robust biomarkers and we can see if we’re seeing an immediate response from the drug. I just… I’d be interested to know, kind of from a methodological point of view, how it works.

Dr James Quinn:

Yeah. So I think, from a methodological point of view, you use the biomarkers that you know already track the disease. So, well, to some extent, you’d obviously have your tau, your amyloid beta ones in there, which we know kind of map up with cognitive decline in a certain way, and then we can then use those plus others that have been used in other disorders, that have been showing really promising… Is it like, for example, a marker of inflammation, how that then responds to different drugs. So I think it’s one of those, it’s definitely something that’s an emerging topic and it’ll probably be interesting to see if it is an emerging topic next year at the conference, where you’re saying, “Okay, we’re looking at lots of different areas of a person’s disease profile and then really trying to track that down in more detail.”

Adam Smith:

Fascinating. I realise, of course, I did skip past asking you about your own presentations, but I’m going to adjust the program round and we’ll come to that at the end. The other talk after Maria about the main themes was Marilyn Albert did the main plenary today. Did you all see that? Did you stick around for…

Sarah Gregory:

Yep.

Adam Smith:

So that was using… She had different longitudinal cohorts and then they were applying combinations of biomarkers, which I found really fascinating, really well presented in a way that even I… I’m not scientific in that way, but I could understand. Particularly, I thought it was when she was talking about NPTX2 combined with a pTau and how you could see five years on that they could predict to increase prediction rates from 71% to 89%, which is obviously… Even I understand those numbers are better. What did you pick up from that? Was there anything to highlight from that talk that you think might be of interest to people?

Dr Clare Walton:

I didn’t really pick up the specifics in that way. Much more that, well, I guess, one of the things I found really interesting was, she kind of started the talk with the consensus in the field is that it’s a long prodromal phase that lasts decades and people, several decades before really having dementia, do have some subjective symptoms and obviously have the pathology. But even that part I questioned because I think, yes I understand how well-documented that is, but I think it’s kind of a consensus in the US very much. But in the UK, speaking to clinicians, I just think there’s a lot more uncertainty about how much we push that kind of prodromal preclinical diagnosis and whether it has any value. So I thought that was just a really interesting kind of geographic comparison that just the opening kind of “let me set the scene” line that she gave was very US-centric, and I think it’s not actually the same across the world that we necessarily frame the problem in the same way.

Adam Smith:

Although the cohorts weren’t all US, were they? There was an Australian cohort in there as well. Was that the only outside…

Sarah Gregory:

I think that was the only outside-US one.

Dr Clare Walton:

Yeah, that…

Adam Smith:

That was the only non-US cohort in that population. What about you, James? Did you [crosstalk 00:15:59]?

Dr James Quinn:

Yeah, I think the few things she pulled out at the end was that really wanting to predict at a patient individual level, which kind of matches up with what I was saying before about this personalised medicine-based approach, to really select patients into the clinical trials that they are going to do best in, which I think is a really interesting approach.

Dr James Quinn:

The other thing I found fascinating was around just where she was looking at tau deposits in patient brains, and showing that you get them at 30 years old, and that kind of blew my mind a little bit. And that they can start… The percentage increases as time goes on in the general population. And then the similar stuff around the amyloid and how that changes from diffuse plaques into neurotic plaques as age progresses, and the need to identify new biomarkers to improve prediction.

Dr James Quinn:

They talked about NPTX2, which is something we’re looking at in our lab. It was really interesting. And then the need to identify blood-based biomarkers as a really easy way of tracking disease instead of having to use CSF in order to treat patients as early as possible. Which is definitely the message coming out of the US, moreso. There’s obviously a big argument to be had around early diagnosis. How actually important is it? Because if we need to start treating patients in their thirties with these tau-targeting therapeutics, that’s a debate for another kind of…

Adam Smith:

Well, particularly if they’ve moved on to more of the lifestyle factors. I mean, I know there’s evidence already about different lifestyle factors having… But if you could start to actually put some real statistics to say, “Right, okay, smoking contributes this many percent,” rather than, “It’s this much. It’s this much.” I think having those early biomarkers might persuade that change of behaviour. Because this is a problem, isn’t it? We know that smoking, eating badly and not exercising are going to contribute to Alzheimer’s and heart disease and diabetes and all the other things, and people still do it. So I guess having more evidence helps.

Dr Clare Walton:

Although, one of the studies that’s been picked up by the newspapers today, that was presented, is from the University of Exeter, led by David Llewellyn and that’s showing that… It was a big study with 200,000 people from the UK Biobank and they were looking at the interplay of genetic risk factors and lifestyle risk factors. And they were showing that even in people who have the highest genetic predisposition, I think they looked at about 20 genes, even in those people, those that followed the healthiest lifestyle could reduce their risk by about 30%, about a third. So I think it’s starting to show that you can almost offset some of that genetic risk by making healthy lifestyle choices.

Adam Smith:

That was… Actually, maybe you can answer the question because I thought this through. What are the genetic risk factors? Because there isn’t… I mean, other than APOE-4, there isn’t an Alzheimer’s gene, is there? So are these genetic risk factors in relation to weight or different health conditions and they contribute to it?

Dr Clare Walton:

So there has been about 20 genes linked to Alzheimer’s disease from GWAS studies, genetic-wide association studies. So they took out the ones that… the rare familial inherited forms of…

Adam Smith:

Right, right. I understand.

Dr Clare Walton:

So they took out those genes that are known to cause dementia in rare cases and they were just using the risk genes. But there is a panel of about 20 genes that have been linked to Alzheimer’s.

Adam Smith:

So linked-

Dr Clare Walton:

And so they use those.

Adam Smith:

And they were the ones that they looked at from the Biobank?

Dr Clare Walton:

Yeah. We don’t necessarily know how much each one of those genes, what their individual risk would be, but they kind of just looked at how many of these genes did you have, and the more you had, the higher your score.

Adam Smith:

Yeah, collectively. Actually they made a point there about you, I’m sorry James, highlighting about the amyloid deposits in younger populations. So I’m going to come to Sarah now, because Sarah, you probably have a good sense of quite a lot of cohorts that… Because that’s one of the things that EPAD does, is bring together cohorts, doesn’t it?

Sarah Gregory:

Yeah. So in EPAD we’ve recruited from other research cohort studies, and then EPAD in itself is a cohort study as well. So there’s just under 2000 people now across Europe in EPAD and we have biomarkers on all of them. So we’ve got amyloid and tau from spinal fluid for everyone and we’ve got future biomarkers that we’re looking at.

Adam Smith:

So how young do you go on your amyloids?

Sarah Gregory:

So in EPAD we go down to 50, and in Prevent some of our participants provide us with lumbar punctures and some do PET scans and that goes down to age 40. So I think as that data… That’s all open access data as well. So as that becomes available, I think that’s going to really add to what was being talked about in today’s plenary session.

Adam Smith:

So, good cohort for you to get your hands on there, James. You can make use of that. Okay, fantastic. So that was Marilyn Albert and she was from the Mayo Clinic because… She was from the Mayo, wasn’t she?

Sarah Gregory:

Just got it here. No, she was from John Hopkins.

Adam Smith:

John Hopkins, yes. Johns Hopkins, you’re right. Okay. So we touched on Exeter there. Is there anything else to say about their presentation today? I think we’ve covered that, haven’t we? Exeter have got quite a few talks, actually. I think there’s a bunch of posters as well. There seems to be quite a large contingent from Exeter presenting over the conference. So what else did you see? Let’s come to you first of all, Sarah. What did you see today, over and above the ones we’ve talked about?

Sarah Gregory:

So I’m going to pick out a couple of the posters I saw, because I’ve been on the EPAD booth this afternoon. So I was mainly in the poster sessions after the plenary. So one was kind of following on from that, looking at physical activity and amyloid in midlife. So the first author is Marta Milà-Alomà. So she’s from Barcelonaβeta and was looking at the ALPHA cohort, which is kind of a sister cohort of Prevent under the Tribeca organisation. And she found that levels of physical activity over 150 minutes a week were associated with a lower amyloid burden on PET, but mainly in men rather than in women, which was quite an interesting finding. So yeah, I thought that one was really interesting, that in their midlife cohort, which is 45 to 75, they’re again finding that physical activity at a moderate level is associated with a lower risk of having amyloid on your PET scan.

Sarah Gregory:

And then another one which was from Inserm in the University of Paris, so [inaudible 00:22:23]. Sorry if I said that wrong. It was looking at visit-to-visit blood pressure changes, so within the person variability, and people who had more variability between their visits had worse cognitive decline and a higher risk of incident dementia. I’m quite interested in looking at variability within the stress biomarkers that we’ve got within Prevent as well to see, does variability within that person actually have a bigger impact, rather than having very, very high blood pressure, very low? Is it the variability that’s a risk? So I’m interested in translating some of those to what we’re looking at within the cortisol data that we’ve got as well.

Adam Smith:

Interesting. There’s been a lot of posters actually. I did manage to have a little look around myself. There was a whole section on registers and recruitment and things like that, but that was quite interesting because we haven’t presented on joint dementia research JC here, but they’ve done some of the same things we have and we’d have slightly better results than they’d had. So I’m going to make a point of seeing and finding out what they’d done differently that we’ve had more success.

Sarah Gregory:

There was quite a lot here this year about engaging with people who don’t typically engage with the registers, I noticed. So a lot about how do you engage with ethnic minorities on registers. That was a really interesting one on using peer-to-peer videos, so getting people from the communities you wanted to engage with appearing in a video so that people are actually seeing people like them as part of research. And that seemed to work quite well, whereas other outreach programs weren’t engaging in the same way. Because yeah, that’s like we find we have a very heavily Caucasian population on any registry we have.

Adam Smith:

Over the first session I met Astrid Suchy-Dicey, who I’ve actually persuaded to join tomorrow’s podcast, and she’s at Washington looking at exactly the same thing as well about indigenous and hard-to-reach populations’ engagement, not just in research but also just in the dementia carers as well. What about you James?

Dr James Quinn:

I really focused on just going to the talks today, but I did go to this really interesting emerging concepts seminar series that was on this afternoon called “Them’s the brakes. DNA damage drives ageing and dementia.” It was fascinating. There was four presenters and the one thing I really liked about it, there was no questions during it and they just went back-to-back-to-back-to-back and then they did questions at the end. It was quite a nice way of doing it because it actually meant the speakers kept to time, which is always a rare one.

Dr James Quinn:

So, I’ll quickly name the four presenters. I’m going to really do a bad job with this first guy’s name, but it’s Jan from Erasmus University. I’m not going to attempt his surname. Then there’s Bess Frost, San Antonio in Texas. Leonard [McKee 00:25:02] who is at University of California, which is in San Francisco. And then there was Karl Herrup who is part of the Alzheimer’s Disease Research Centre in Pittsburgh and essentially that, as I summarised in a tweet earlier today, in two lines, DNA is constantly damaged in all cell types and aging is an accumulation of unrepaired DNA. DNA damage occurs at an individual level. Alzheimer’s disease may occur at an individual cell level. So what they’re trying to say is that each cell is kind of having its own story and that’s what they really want to try and unpick in a little bit more detail, which I found quite fascinating as a kind of idea that you’re not looking at the whole brain, you’re looking at each cell, what is happening to that cell.

Dr James Quinn:

Each cell has a different type of Alzheimer’s disease kind of thing. It was a very interesting idea-

Dr Clare Walton:

It makes the problem sound a little bit [crosstalk 00:25:55].

Dr James Quinn:

Yeah, it does. But yeah, and they were like, “All of the answers and all the treatments are right here. We just need to work out what on earth they are.” So it was quite fascinating. It really opened up more questions than really gave answers and they…

Dr James Quinn:

Yeah, there was a lot of quite generic things, looking at DNA damage, how that can drive neurodegeneration in different models. But they did show this fantastic video about dietary restriction and that’s potential role in preventing neurodegeneration. They had this, it was an end of one experiment, but this little girl, I can’t remember her name for the life of me, but what they were showing is that she had this gene mutation that caused her to get lots of DNA damage. It was like seven years old, struggling like to do any kind of speech movement, everything, and then they gave her dietary restriction and she got better. Obviously this is not a full clinical trial, so please don’t try doing this at home, but there was some really interesting preliminary work that I think needs some further evidence base. And it got a lot of interest in the room, but that was my kind of-

Dr Clare Walton:

There’s quite a lot of work on dietary restriction and aging, but not then drawing it to neurodegeneration. So I guess maybe we need to bring that research community into the conference next year.

Dr James Quinn:

Yes. I think that’s a very sensible idea, because what they’re basically saying is that DNA damage is causing aging or it’s kind of become part and parcel with it, but that dietary restriction can prevent that DNA damage. So there’s the kind of hypothesis that they were suggesting.

Dr James Quinn:

And it was interesting, you got a lot of like… I said interesting so many times, but lots of interest from the people in the room as well. So yeah, I had a lot of questions, more questions than answers leaving it, but I think that’s what conferences are for.

Adam Smith:

Did you ask them? Did you stand… Did you take the mic?

Dr James Quinn:

Well, I ran away to get a coffee, but you know, it was one of those… Because I think a lot of my questions are around, “Oh, can we look at potential biomarkers of DNA damage?” I don’t know if any of those exist, but I think that’s something could be really important.

Adam Smith:

So do you know what? And that is something we absolutely… All the sessions, I’ve been to today, the only people asking questions have been more senior people. I think the early-

Dr James Quinn:

I did ask a question this morning though. I’m just saying…

Adam Smith:

Well done. Okay. Good. Because early career researchers, I think they have lots of questions written down and then a little bit too shy or worried about looking silly by asking a wrong question and don’t actually stand up to put those through. And that’s noticeable here because once again, I said this last year, compared to coming to this conference seven, eight years ago, the number of early career researchers here compared to more senior people is hugely outnumbering now, I’d say. Young people under the age of 40 and early career researchers here is massive compared to the older people. It’s not just older people. I’m picking on age there, that sounds bad. More senior people. And I think it’s through funding like Alzheimer’s Society’s increased funding and through Alzheimer’s Association here, that’s brought all this new generation of researchers and new ideas, like from James and Sarah as well, who are bringing these things that we haven’t thought about before.

Dr Clare Walton:

But I think you’re right. Early career researchers are definitely really well-represented on the program and I find that really encouraging when it’s not professors presenting their PhD students’ work, it’s the PhD students. But I think the culture around the questions, it’s just a bit intimidating. These are huge rooms and there’s so many people and the pace of the talks are so fast that if you are earlier in your career and you haven’t been to five of these conferences and you don’t know all the context, you just feel a bit out of your depth sometimes. And that’s something we probably need to change.

Adam Smith:

You could use a fake name at the start. But if you get it wrong, it’s like, “God, that person from…”

Sarah Gregory:

I went to the R&D forum and they had an app and you just submitted it. Obviously there’s so many rooms there that it’s difficult, but you just submitted it on there. So it meant that even if you didn’t want to get up in front of everyone, you could still get your question asked, which was quite a nice way around it, I thought.

Adam Smith:

Yeah, that’s a good idea.

Dr James Quinn:

There’s been some nice studies that have shown that if an early career goes up first, a lot of other early careers will then feel it’s okay to go up. And it’s the same with the sex of the person going up as well. Like men asking majority of the questions. If a woman goes up first, more women ask questions. And I’ve been to conferences where, I remember Tara Spires-Jones doing this once at a conference, she was like, “The first question is going to be from an early career researcher. I’m not accepting one from a professor.” And I think sometimes someone doing that makes it so, “Okay. I should think of a question now.” I mean, it puts you on the spot a little bit, but I think that opens up the room a lot better.

Adam Smith:

So we could throw that challenge out there for anybody that’s here at the AIC conference over the next three days. Early career researchers, come on, be brave, stand up, ask that first question.

Dr James Quinn:

And I did it and I didn’t fall apart and-

Sarah Gregory:

You survived.

Dr James Quinn:

Yeah, I survived and the guy, I met him last year and he came up to me after and said, “Oh, that was a good question.” And it helps a lot because it can help build those networks a little bit.

Adam Smith:

Absolutely does and I think, as we talk about all the time, these conferences are a fantastic opportunity to network and meet people and don’t be afraid, talk to people, do approach speakers afterwards. And it’s not just this conference, of course, it’s all the other ones that we see too. So I missed earlier. We’ve got a couple of minutes left. Sarah, are you presenting this week? Your own work? What are you-

Sarah Gregory:

I have a poster on Tuesday. So it’s some work I did with Actinogen who are in Australia, a pharmaceutical company, and it was just prior to my PhD. So we were looking at 11β-hydroxysteroid dehydrogenase type 1 inhibitors, which is a drug class that acts to reduce the change from cortisone, which is inactive, to cortisol. And so we were doing a systematic review to see what areas in animals has this been studied and in what areas in humans. And the main findings of it were that, mainly from within animals, Alzheimer’s is a big area of interest for these inhibitors. Obesity, diabetes and metabolic diseases are really big areas and they’ve moved to human trials as well, as have some of the Alzheimer’s drugs. And psychiatric disorders, particularly depression and anxiety. So I think it’s a really interesting area to look at, in terms of what I’m interested in my PhD, that it could be relevant for treating Alzheimer’s disease, but it also could be relevant for some of the diseases that we know are risk practice outside of this disease as well. So yeah, I think there’s a potential there to explore them as preventative.

Adam Smith:

So have you already presented that or is that for-

Sarah Gregory:

It’s on Tuesday.

Adam Smith:

That’s on Tuesday?

Sarah Gregory:

Yep.

Adam Smith:

And sorry, did you say-

Sarah Gregory:

It’s a poster.

Adam Smith:

It’s a poster. So what’s your poster number?

Sarah Gregory:

I think it’s number three. It’s in the therapeutics, so it’s one of the very first [crosstalk 00:32:38].

Adam Smith:

Okay. So make a point of going and seeing Sarah’s poster on Tuesday, if you’re here at the conference. And James?

Dr James Quinn:

I just found the photo of my poster presentation number, just because I thought you’d ask. But yeah, I’m presenting a poster on my research for my PhD, so hopefully it’ll be my last time doing that. But it’s been nice to kind of put that to bed a little bit and hopefully more work is going on in my old lab, but… So yeah, my title is Proteolytic Cleavage of Tau in Corticobasal Degeneration and Progressive Supranuclear Palsy Pathogenesis. So these is basically looking at one of the post-translation modifications of tau in two of these quite rare forms of dementia. And I will be presenting that on Wednesday. My poster number is 524 and I will be around all day. So feel free to come and take a look if you are here at the conference and you’re listening to this podcast. If not, I’m very sorry, but yeah, ask me on Twitter and I’ll be able to send it to you.

Adam Smith:

Well we’ll talk to that. I was going to… Sorry. Clare, how about… You’re not presenting?

Dr Clare Walton:

No, no, I’m not presenting but I just wanted to say, Alzheimer’s Association, Alzheimer’s Society and several other funders are having a reception for early career researchers on Wednesday evening, 6:00 til 8:00 at the InterContinental Hotel. So any early career researchers listening to this, come along and come and meet us.

Adam Smith:

Wednesday, 6:00 til 8:00?

Dr Clare Walton:

Wednesday, 6:00 til 8:00 at the InterContinental.

Adam Smith:

Can I give you some leaflets as well on our podcast and website, to get everyone to come to…

Dr Clare Walton:

Of course. Yeah.

Adam Smith:

Because we list all the… We should say at our website, we have all the funding opportunities from Alzheimer’s Society and Alzheimer’s Research UK and other charities. Not just UK-based research funding opportunities either, but from elsewhere around the world, is listed on our website at dementiaresearcher.nihr.ac.uk.

Adam Smith:

Well, thank you very much everybody. That’s all we’ve got time for. And if I’m honest, we’re keen to wrap up because tonight’s the welcome evening, which is at the Universal Studios and we’re all excited to go to Universal Studios.

Sarah Gregory:

Definitely excited.

Dr Clare Walton:

The Harry Potter ride, definitely.

Sarah Gregory:

Harry Potter. That’s all I’ve heard all day, Harry Potter.

Dr Clare Walton:

Yeah.

Adam Smith:

That’s riding a broomstick. But honestly, do you know, is it a scary ride? Because I’m not big on scary rides.

Dr Clare Walton:

To be fair, that’s why I want to do that one. Because I think there’s a Jaws one and I’m not keen on that. But Harry Potter, how scary can it be?

Adam Smith:

I don’t know. If it’s roller coaster burst, I’m not really into it. But if it’s kind of, “Woo-hoo. Look VR, isn’t it wonderful to embrace it?” then I’m all up for that. But I’m not…

Sarah Gregory:

I think there’s a show that you can watch at 9:15-

Adam Smith:

There’s a show?

Dr Clare Walton:

That’s about your level of excitement, Adam.

Adam Smith:

Oh my, there’s a show.

Dr Clare Walton:

You can go to bed early and…

Adam Smith:

With the kids.

Sarah Gregory:

It’s a dark arts show, though.

Adam Smith:

Oh, okay. Well I’m not going to confess to having brought my wand with me, but… So, thank you very much to our panellists, Sarah, James and Clare. Listeners can get in touch with all our panellists today via Twitter. So Sarah, what’s your Twitter address?

Sarah Gregory:

@gregorysarah.

Adam Smith:

James?

Dr James Quinn:

@tweetwithquinn, but I’m going to plug our new lab Twitter, which is ACTRU, so that’s actru_MGH as well.

Adam Smith:

Okay. Clare?

Dr Clare Walton:

@cawalton.

Adam Smith:

Fantastic. Okay, so again, time to end this podcast. Thank you very much for joining us today. We’ll be back tomorrow as well with more panellists talking about day two. Please remember to subscribe and leave a review on our podcast through SoundCloud, iTunes, and on Spotify. And again, I think you can probably pick up on more of the conference highlights, looking on Twitter using the hashtag AAIC 19. We’ll give you more of a view and we’ll be back tomorrow with day two. Thank you very much.

Voice Over:

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

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