Podcast – AAIC 2022 Day Two

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.

Dr Isabel Castanho:

Hello, welcome to the Dementia Researcher Podcast on location from the Alzheimer’s Association International Conference, or AAIC, in sunny San Diego. I’m Dr. Isabel Castanho, and today I have the pleasure of guest hosting the second of four show series being recorded each day at AAIC. As part of this series, we’re sharing highlights with fantastic early career researcher guests. Today, we’re going to cover the second day, although with so much pre-conference activity, you could argue this is day four. But to clarify, I’m talking about Monday. Before we start, let’s make some introductions. For those who don’t know me, I’m a research fellow at Beth Israel Deaconess Medical Center, or BIDMC Harvard Medical School in Boston, working with Dr. Winston Hyatt. In my current position, I’m investigating protective mechanisms to Alzheimer’s disease with a special interest in single cell and spatial transcriptomics. I am thrilled to be at AAIC in person this year for lots of reasons.

Dr Isabel Castanho:

One of them being because it always have a special place in my heart really after being an ISTAART student volunteer, now called ambassador, twice during my PhD. If you’re a student listening to this podcast, make sure to check how you can apply to become an ISTAART student ambassador next year. I guarantee that it is lots of fun and absolutely amazing for networking and for making friends for life. Let’s move on to our brilliant guests. I’m delighted to introduce three people who are entirely new to the show, Dr. Annalise Rahman-Filipiak, Dr. Bhargav Nallapu, and Dr. Connor Richardson. Hello, everyone.

Dr Annalise Rahman-Filipiak:

Hi.

Dr Bhargav Teja Nallapu:

Hello.

Dr Isabel Castanho:

Welcome. Annalise, tell us about yourself please.

Dr Annalise Rahman-Filipiak:

Well, first, thanks so much for inviting me. This is really exciting. So I am a clinical neuropsychologist and I work over at the University of Michigan with the research program on cognition and neuromodulation based interventions. I’m also an assistant professor with the Michigan Alzheimer’s Disease Research Center, and most of my work focuses on culturally informed biomarker disclosure practices, so basically thinking about how we communicate about biomarker results to diverse populations.

Dr Isabel Castanho:

Wow. That’s really interesting. Thank you. Bhargav, go ahead and introduce yourself please.

Dr Bhargav Teja Nallapu:

Yes. To begin with, thank you for having me here, and I’m really glad to be here. I’m Bhargav Nallapu and I’m post-doctoral researcher with Albert Einstein College of Medicine in department of neurology. I work with Dr. Rezarti and Dr. Lipton, and our team uses machine learning to understand the predictive power of biomarkers in terms of disease progression, or prognostic of NAD. And yes, I’m really excited to be in this conference and to be talking with you all.

Dr Isabel Castanho:

Thank you. Connor, let’s come to you.

Dr Connor Richardson:

Hi, I’m Connor. Again, thank you for having me. This is really exciting. I’m a post-doc at the University of Newcastle in the UK, and I work on the cognitive function and aging studies, which is a very large, multi-center population representative cohort of older people in the UK. I work with professor Fiona Matthews and we primarily look at modeling longitudinal risk of dementia across time in the UK at a population level. But we don’t just work with dementia. We look at a whole range of health outcomes for older people at the moment, as well as dementia. I’m also looking at loneliness and depression caused by the COVID-19 lockdowns.

Dr Isabel Castanho:

Wow. This is really interesting. I’m surrounded by brilliant scientists. So I’m actually going to break the ice for a little bit now by starting with asking you about Sunday’s welcome reception. This is a little bit of cheating because it’s not about Monday, but I had so much fun and I would like to hear if you guys had fun. For our listeners that were not there or here, the reception was California themed with several cities represented in different areas of the venue, and there were live statues that were absolutely incredible. I was particularly fascinated by the lady dressed as a water fountain who never lost character by one moment. And I think my actual favorite part of the night was the Hollywood area that had a red carpet with paparazzi taking photos of you and asking you questions about your new movie while you walked down the red carpet. That was so much fun. What about our guests? Did you enjoy Sunday’s reception?

Dr Annalise Rahman-Filipiak:

It was something else for sure. Not a reception that I’ve seen at some of the conferences I traditionally attended. This is my first AAIC in person. Nothing says Alzheimer’s disease research like a lady fanning herself in a cocktail glass. But yeah, it was amazing to see just the entertainment and the interactions. People really got into it.

Dr Bhargav Teja Nallapu:

Yes, it was really amazing. And I agree with you. One of my favorite parts was the paparazzi taking photos, and I’m glad that I got my niece excited. When I shared that, she thought, “Okay, this is how scientists are received.” So that’s great. So I got her excited to get [inaudible 00:05:25].

Dr Annalise Rahman-Filipiak:

Good PR for us.

Dr Connor Richardson:

Yeah, it was excellent. It was definitely the first kind of reception that I’ve ever been to at a conference. And it was awesome because you met people that very first day and then by the nighttime you’re dancing away with them, which was just excellent.

Dr Isabel Castanho:

Yeah. I’ve seen quite a few reception from AAIC. AAIC, I guess, goes a bit overboard with that, but it’s fun because it actually makes us interact with each other, meet other people, network. So it’s really, really fun. Okay. So back to work. All of today’s guests are presenting this year at AAIC. Connor, you presented on using machine learning for future ranking and classification. Do you want to tell us more about it?

Dr Connor Richardson:

Yeah. So what I presented today is really the first stages in following up a paper that myself and a group at Newcastle and Sheffield University collaborated with University of College, London. And I mentioned before where I work with the cognitive function aging studies. So as well as being a large population cohort that collects a lot of demographic data or in health data about participants. It also has quite a sizable brand bank. So we have about 600 brands in the [inaudible 00:06:43] brand bank. And what we published last year was updating our dementia risk models for new neuropathologies, which we’ve, over recent years, been able to stand in for which we couldn’t previously. We also identified a brand new pathology caused by serum amyloid protein, serum amyloid component P. So we wanted to try and again update our methodologies and try and move into this machine learning space.

Dr Connor Richardson:

So we tried to go a little bit against the grain of how machine learning’s normally done. So we took a different approach from trying to model as many different neuropathology variables as we can and see what happens. We took what we’d been working on from our classical epidemiological model into things that we knew had a robust risk profile for dementia and tried to put those six variables which we knew about, including the new one for SAP, into a machine learning model, and to really see whether this kind of machine learning approach tells us anything different or anything more than what our classical epidemiological models did. We found a couple of pretty cool findings. So we found that using things like decision trees, you get an idea of at what points certain neuro pathologies become more important than each other.

Dr Connor Richardson:

So we found that serum amyloid component P was quite important in differentiating dementia risk in people who had quite low [inaudible 00:08:16] staging, but we also found quite a few issues with it. We found that in comparison to using the epidemiological modeling we did before, just your normal logistic regression models, the machine learning didn’t really add a huge amount of information to what we had before. And actually, in certain neuropathologies where you have quite low numbers in the cohort, like Lewy bodies, it actually throws out some quite strange results. So it told us that Lewy bodies had the least importance of determining dementia risk, which is obviously not right if you have Lewy body dementia. I’ve had a lot of interesting discussions about whether people approach this kind of determining dementia risk from a statistical epidemiological point of view or a data science point of view, and both camps seem to have quite differing opinions on how these models work. But yeah, it’s been really interesting.

Dr Isabel Castanho:

Oh, interesting. Bhargav, I know you also do machine learning and you presented a poster on plasma based biomarkers and you’re also giving a lightning presentation on Wednesday. Want to tell us more about that work?

Dr Bhargav Teja Nallapu:

Yes. Sure. And actually, to start with, Connor gave a very good overview of the trade offs and the benefits of using machine learning in this field. And I, for myself, we focus on AD pathology and the data from biomarkers and cognitive assessments and we try to use machine learning to understand the progression or the predictive power of these biomarkers. But with keeping in mind that we are not looking for some best performing models with complicated machine learning behind them. At the end of the day, it’s the clinical relevance that we are looking at, especially when you talk about biomarkers and the different kind of complexities involved in plasma or CSF or MRI. So that’s what we are trying to understand what each of these contribute to our ability to understand the progression of disease. So that’s actually kind of work that I presented related to plasma based biomarkers.

Dr Bhargav Teja Nallapu:

And on the other hand, the lightning presentation is going to be on understanding the effect of alcohol on cognition. And why that is something that we felt was important to understand is because alcohol is one of the biggest modifiable risks in dementia. And moreover, we were actually observing the differences of effects probably in sex is differently or in the status of Abeta in their brain, different effects. So that’s one of the reasons we were interested in understanding these effects of alcohol consumption on cognition and in different sexes. So that’s the lightning presentation on Wednesday. So yes, it’d be great if you could attend that.

Dr Isabel Castanho:

Thank you for sharing. And before we started recording, you actually shared something on when you think about the best biomarkers, you actually take into consideration how easy it is for the participants or for people that you’re trying to use them on. Do you want to tell more about that?

Dr Bhargav Teja Nallapu:

Exactly. Thank you for raising the point, because that’s exactly our goal in this endeavor is not to come up with a complicated model that achieves some best performance. In fact, I started this work with a simple table that gives you an idea of, what is the ease of acquiring this biomarker data and what is the cost involved in it and what is the discomfort involved in it for a patient? And I’m trying to understand, how does this map to their contribution in our analysis and in models? How far is plasma getting compared to a neuropsych assessment or an MRI? We all know that PET scans can be very powerful to understand or MRI can be powerful, but the question is, okay, but how far can plasma get? When is it good enough?

Dr Annalise Rahman-Filipiak:

What’s the incremental predictive validity of that information over stuff we can acquire precisely easily?

Dr Bhargav Teja Nallapu:

Precisely. Yes. So that’s one of the important lines we are taking in doing this modeling work.

Dr Isabel Castanho:

I love that. Thank you. Thank you for going through that. Annalise, you are giving a presentation on Thursday. Want to share some more details with us and why our listeners should not miss it?

Dr Annalise Rahman-Filipiak:

Sure. So I am co-chairing and presenting in a session that will bring together some researchers from University of Michigan, University of Pittsburgh and University of Wisconsin, almost all of whom are early careers, so shout out to all of them, but we’re going to be talking broadly about considerations for PET biomarker disclosure. We all work together to some extent in the Advisory Group for Risk Evidence Education in Dementia, or AGREED, which is an international work group that incorporates stakeholders, patients, caregivers, clinicians, researchers, others, all who care about communication of results back to research participants or patients. And so we’re going to be talking a little bit about the steps that need to be taken for ethical and safe biomarker disclosure, the potential impact of that information in folks’ lives, how to incorporate diversity factors in the way that you do this. I know it is the last session of the conference, but change your travel plans, y’all. And come to it. That would be great.

Dr Isabel Castanho:

Thank you. That’s really interesting. Okay. Let’s get down to business on highlights from Monday. For those who are new to the format of these shows, we really just go around and talk about our favorite bits from the conference. As I’m hosting, I thought of starting by sharing one of mine first when I was preparing for this podcast. Unfortunately, I did not have much room to breathe yesterday because I stayed by my poster all day that turned out to be very popular, much more than I was expecting.

Dr Isabel Castanho:

So my highlight is going to be a bit biased since I did not get the chance to see many of the presentations I planned to see. I really enjoyed The Plenary, by Dr. Thomas Beach, who called our attention into the importance of definitions and classifications in neurodegenerative diseases and gave us a beautiful overview of neuropathologists throughout history, comorbidities, highlighted the good and bad sides of reductionisms. I really recommend his talk if you haven’t seen it yet. I know that I will re-watch it by taking advantage of the fact that it was recorded and it’s a hybrid format. What about our guests? What are your highlights from yesterday, Annalise?

Dr Annalise Rahman-Filipiak:

In line with what we’ve been talking about, I think a lot of these complex modeling and computational modeling, machine learning approaches have the opportunity to use large data sets. I think a problem of some of those large data sets is a lack of representation from underserved and underrepresented communities. So I was really excited to attend the featured research symposium that talked about the crisis of under-representation in ADRD studies. Just such a rich, amazing presentation. And I think they balanced contextual information, historical information with really tangible current recommendations very well.

Dr Annalise Rahman-Filipiak:

So some of the folks that I want to highlight from there, Kylie Smith is a historian in nursing, I think, at Emory, and she started that featured research symposium really highlighting the historical context. I think many of us know about some of the more obvious and egregious ethical atrocities that have been enacted upon the Black community, things like Tuskegee, but she presented some really nice data that was drawn from primary data, historical data from asylums in the South, the American South, just showing racialized diagnostic procedures and how that really colors the data that we have today, the way we diagnose different individuals and what we quote unquote know about race differences in different diagnostic categories within dementia. So I think she presented that information beautifully.

Dr Annalise Rahman-Filipiak:

And then within that presentation as well, there were some really great tangible recommendations from people like Dr. Jackson, so Jonathan Jackson, from Jen Langer, who is at U Pitt, and from a few other folks there about really empirically supported strategies for engaging underserved communities. So they presented relational organizing strategy, which really comes from the political space, and just reflecting on how that is such an important, but time consuming and effort consuming practice and how really, what that points to is that we need to be budgeting that time and energy and effort into our timelines, into our grants, into our tenure plans, all of those things, if we really want to do this well.

Dr Annalise Rahman-Filipiak:

There were some other speakers, so Jason Flatt and Crystal Kittle, who were from University of Nevada, Las Vegas, and they presented some really great data and suggestions about sexual and gender minority populations, and really thinking about how intersectional identities can influence your cumulative risk for Alzheimer’s disease, but also the way that you experience that diagnosis, the way you provide care, the burden. So one take home that I thought was really powerful from Crystal’s presentation was this idea that caregivers who are sexual and gender minorities are, over time, navigating their own identities and maybe the conflicts that they might have had with their parents that they’re now taking care of, and at the same time, experiencing the well known discrimination, implicit and explicit, around healthcare for those individuals. So I just thought it was an incredibly comprehensive and powerful set of talks. I really appreciated it.

Dr Isabel Castanho:

Wow. Thank you for giving us so many details. Hopefully our listeners will check all those talks. What about you, Bhargav? Anything that you found particularly fascinating yesterday?

Dr Bhargav Teja Nallapu:

Definitely a bunch of them. Actually, before that, I really would like to thank Annalise for highlighting those talks and the work. Because on one side, we are aware that one of the underlying themes of this conference, we have been hearing about more diversity that is needed in this research, but what Annalise highlighted just now is not only the diversity in the clinical research we are doing, but the importance of educating these demographics. And I think that’s one of the crucial things that you also pointed out that was there in many of these talks. So I find it really amazing. And then for myself, I found a couple of them really interesting at a high level, particularly the research on plasma biomarkers. There was a hybrid symposium that was in the morning, which was titled The Road to Clinical Implementation of Plasma Biomarkers, which I believe all of us are really excited and interested to know more about.

Dr Bhargav Teja Nallapu:

And all four of them, there was Dr. Charlotte Tenneson and Dr. Oscar Hansen, and one of the very interesting studies actually involving Colombian cohorts that was presented by Dr. Yaki Kiros. And then finally, it was Douglas Glasco, Dr. Douglas Glasco who highlighted the standardization, even in the process of taking plasma research and plasma biomarkers on the way to clinical applications, Dr. Douglas Glasco highlighted the importance of standardizing these and importance of having some risk score predictions. I thought the whole session was amazing to begin with. And then on the other side, since my background is machine learning, I was also looking out for different exciting works on that front. What I found interesting was a round of oral sessions where it was mostly concentrating on identifying subtypes within the AD pathologists, which I found interesting because we all know how heterogeneous AD pathology is.

Dr Bhargav Teja Nallapu:

And then when you’re using these methods to identify these subtypes and understand how they’re differing in terms of progression or in terms of their imaging atrophy in the brain, that I found to be a very promising direction. Because like I mentioned before, one of the challenges of using machine learning is the explainability of it. That is the most important thing we need to concentrate on when we are trying to apply that in a clinical context. And when I saw this set of talks, in fact, one of my colleagues, Dr. Kellen Peterson, presented one of the methods on that and researchers from the Amsterdam Alzheimer’s Department, I think it was led by Dr. [inaudible 00:21:07]. And I also heard actually, she gave a very great talk on digital biomarkers and my supervisor pointed out, Mr. Darko Azati, pointed out that he was really impressed by the pipeline of digital biomarkers they have.

Dr Bhargav Teja Nallapu:

So this whole field is super exciting for me, one, because I’m from that background. And two, I also think if it’s done in the right way with the correct clinical implications and relevance [inaudible 00:21:35] into it, I think it’s a very promising method that’s going to come out for the field. And last, I would like to highlight one other interesting thing I saw in the poster sessions, which I did not think of before coming to the conference, is the care side of this. So we are all talking about the scientific research side of this, but I found it really interesting that there was a section of posters which were concentrating on the patient care after diagnosis and I found it really pleasing to see that, okay, this is also a very crucial aspect, and I was happy to see many posters on that front.

Dr Isabel Castanho:

Right. Yeah. Actually, on the first day on Sunday at lunch, I ended up sitting in the same table as a participant from ADNE, and that was fascinating to hear about her side. So different to care, but even it was so nice for me to see participants here with us and sharing their concerns and their feedback. That was really amazing. So thank you.

Dr Bhargav Teja Nallapu:

Exactly. That’s what we want, right? A patient-centric research that ultimately, it’s them that we want to benefit from.

Dr Isabel Castanho:

Exactly.

Dr Annalise Rahman-Filipiak:

Yeah. It keeps us very grounded in aligning our priorities with those of patients, of caregivers, of others in the community.

Dr Connor Richardson:

Yeah. When I studied for my PhD actually, I was funded by the Alzheimer Society in the UK, and they do a similar, a much smaller scale conference to this, but it’s quite unique in that half the people they invite are researchers. The other half of people they invite are their volunteer teams. So you go to the conference, you meet all the volunteers who raised the money and it’s an amazing experience because you realize how close it is to the people, how much it matters to people.T he first few times I went, it was actually a little bit emotional because you meet people and they’re thanking you and they’re like, “Thank you so much for what you do.” And like you say, it’s totally grounding and you think, “Oh my goodness, what I do is nothing compared to the things you’ve been through.”

Dr Annalise Rahman-Filipiak:

I also think it sometimes highlights for me how our training really lacks communication to the lay community and training in that aspect. I think we’re really good at giving scientific talks and writing academic papers and that kind of thing but we often don’t take the time to train effectively on lay communication. One of the reasons why podcasts like this are so important, but it’s great to go out there and do some of these community talks or just interact with your participants to share your results and find out that the real question is, how does this impact my life on a day to day or the lives of those in my community? So I think that’s really pushed me to think more critically about how to do that.

Dr Isabel Castanho:

I agree. And I share your thoughts, Connor. My PhD was also funded by the Alzheimer’s Society. I did it at the University of Exeter. And I actually share shared in the past with the Alzheimer’s Association, how even Alzheimer’s Research UK also usually does this at the conference. And for me, that’s such a big highlight of the conference when I hear someone that experienced dementia at some level, either them personally or someone close to them. And I agree, Annalise, that actually I keep saying it actually takes us out of our day to day challenges with experiments and grants and papers and reminds us why we’re doing this, and it’s so great.

Dr Connor Richardson:

Yeah. Well, I think if I could just jump at one of my highlights from yesterday, I completely agree with Annalise. I thought the under-representation in dementia research was just an outstanding symposium. And there was something Jonathan Jackson said that really stood out to me and it adds to what we’re taught about now is that as researchers, we know so much about this one niche thing that we study and sometimes you lose sight of the broader aspect of it. As a biostatistician myself and working on these large population cohorts, we say all the time, “This cohort’s representative.” And in some ways, in a lot of ways, it is. In other ways, it’s probably not. And I think sometimes, you feel, as a biostatistician, that you’ve got to take account of everything.

Dr Connor Richardson:

And what Jonathan said was, “Well, you don’t because you’re trained as a statistician. You’re not trained in the historical perspectives of why there’s so many inequities, why these inequities exist, and you shouldn’t be expected to know all that.” And I think one of the important things he said was that we really need to broaden the team and you shouldn’t be a biostatistician that has an expertise in how to approach ethnic minorities. We should be broadened how to say, “Well, we need someone who is an expert in these things and bring them into the team and they can advise on these things.” There shouldn’t be an expectation of, well, you need to understand everything, because we can’t understand everything. You need people to advise on these things. But I thought that symposium on the whole was just fantastic.

Dr Connor Richardson:

And Jason Flatt’s from the University of Nevada, I thought’s, talk was amazing. And I just thought it was so refreshing because he spent a long time talking about the terminology that we use for sexual and gender minorities. I’m a gay man myself and I just thought, “Oh my God, I am so uneducated.” This is the community that I’m a part of. I never think about these things. And there’s so much that you don’t think about. And I just thought it was so refreshing to hear someone explain things like terminology and how we talk about these groups in such a calm and reflective way because it’s all over the media at the moment. These discussions get so hot and it can cause so much hurt to people and it was just so refreshing to hear someone describe it in such a calm, collected way.

Dr Annalise Rahman-Filipiak:

Can I add a comment to that?

Dr Connor Richardson:

Yeah.

Dr Annalise Rahman-Filipiak:

I think what you’re saying is so important, because even in reflecting in my own journey in research, language is so important and I think it’s also a huge barrier for people. Not knowing the correct terminology in this space where it is really hot and it’s a tough climate, some people just avoid it. They avoid studying those populations, talking about those populations because they don’t know how to talk about it effectively. I think, as you said, Jason’s presentation and others were so great at taking the time to go through that. I think he actually has a… There’s a follow up symposium. I think it’s 14.6A. If I’m remembering correctly, it’s tomorrow afternoon, where they said they’d be going through some of that in more detail. So preview for tomorrow.

Dr Connor Richardson:

Yeah. Even just the science behind it was just stuff that I didn’t even know. I had no idea how much higher prevalence of dementia is in LGBT and transgender communities. You think of it in the abstract of, all minorities have issues in the specific issues in how they approach care and being underrepresented by health services, but I’ve never really thought about in the specifics. It was really eye opening, and like I said, just something I’d never thought of. And I think that’s what it’s all about really is you come here expecting to sit in something about plasma based biomarkers and you get your mind completely opened up to whole broader issues and it’s just fantastic.

Dr Isabel Castanho:

Thank you, Connor. Okay. That is all we have time for today unfortunately. This has been a blast. It was a real pleasure to host these brilliant scientists. You can find bios and Twitter links for today’s guests, including myself, on the dementia researcher website at dementiaresearcher.nihr.ac.uk. I would like to thank our guests, Dr. Annalise Rahman-Filipiak, Dr. Bhargav Nallapu, and Dr. Connor Richardson. Thank you so much for being here today with you.

Dr Bhargav Teja Nallapu:

Thank you.

Dr Isabel Castanho:

And I would like to thank Dementia Researcher for inviting me to host today’s podcast episode. Thank you for the opportunity. It was a real pleasure to have a chat with our fabulous guests today. To our listeners, please remember to subscribe and come back tomorrow for more reflections from day three of the conference. You will also find a massive amount of information on social media using #AAIC22. So A-I-C-C two, and you can also go to alz.org/aaic for more information. Thank you, and see you around.

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.

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