Podcast – AAIC 2021 Round-up – Live Plenary

Adam Smith (Introduction / Voice Over):

Hello, and thank you for tuning in. In this very special recording, we’re sharing the AAIC highlights session that was recorded live, online and in Denver during the AAIC on Friday, the 13th of July. Session chairs, Percy Griffin and Rebecca Edelmayer, spoke to speakers Alexander Ehrenberg, Wagner Brum, Karen Dorsman, Maureen Okafor and Anna Volkmer to discuss their highlights from the week. Please bear with us as the sound quality is not always as great as we would like, but this was a live session and we’re very grateful to the Alzheimer’s Association and ISTAART for sharing the recording with us so that we can share it with you. We hope you enjoy the show.

Dr Percy Griffin:

Hello. My name is Percy Griffin.

Dr Rebecca Edelmayer:

And I’m Rebecca Edelmayer. Welcome.

Dr Percy Griffin:

And on behalf of the Alzheimer’s Association, it’s a pleasure to welcome you to the AAIC highlights session. We have seen a wealth of stellar research on display at AAIC, and in this session we will hear from a panel of five early career researchers regarding what their AAIC highlights have been. If you didn’t get to see any of the research that we mention, there’s no need to miss out with all the scientific sessions available on demand for 30 days.

Dr Percy Griffin:

We do have a lot to cover here today, so we’ll probably just start by introducing you to our panel of researchers. Joining us in person, here in Denver, is Alex Ehrenberg. Alex started at the University of Southern California Memory and Aging Center as a staff researcher in the lab of Professor Lea Grinberg in 2013. He now has dual roles as a researcher in the Grinberg Lab and as a PhD candidate at Berkeley’s Helen Wills Neuroscience Institute. Alex’s primary interests are in the evolution and life history factors that influence early patterns of selective vulnerability in neurodegenerative disease. And, he’s an executive committee member of the ISTAART Neuromodulatory Subcortical Systems, a special interest area of here.

Dr Rebecca Edelmayer:

And we’re also virtually joined by four other speakers. We have Wagner Brum on the line. He is a joint MD/PhD student between the Federal University of Rio Grande do Sul in Porto Alegre, Southern Brazil, and the University of Gothenburg in Sweden. His main research interest is understanding how fluid biomarkers can track Alzheimer’s disease clinical, biological progression, and how they can be implemented in clinical practice and trials. Wagner is passionate about connecting with the international research community, which has led him to join the ISTAART PIA to elevate early career researchers as the South America Executive Committee Representative. We also have Karen Dorsman on the line. She is a doctoral student in clinical psychology at the University of Texas Southwestern Medical Center in Dallas. And Karen is a dedicated volunteer community educator through the Alzheimer’s Association of Dallas and Northeast Texas chapter.

Dr Rebecca Edelmayer:

On the line we also have Maureen Okafor, a postdoctoral fellow at the Goizueta Alzheimer’s Disease Research Center in the Department of Neurology, Emory University School of Medicine in Atlanta, Georgia. Of current interest to her are the design and conduct of clinical research centered on cognitive aging, including vascular, metabolic and biomarker contributors to neurodegenerative diseases. She is a member of the Alzheimer’s Association ISTAART Clinical Trials Advancement and Methods PIA Executive Committee. And last but certainly not least, we do have on the line Anna Volkmer. She is a senior research fellow and lecturer at University College London. She leads research developing novel interventions for people with dementia, particularly rare dementias such as primary progressive aphasia. She is a senior speech and language therapist working at the National Hospital of Neurology and Neurosurgery, University College London Hospital.

Dr Rebecca Edelmayer:

We welcome you all. Thank you so much for joining us today.

Dr Percy Griffin:

Each panellist has a different research purpose. And together with them, we will be covering all of the different AAICs. It’s been quite different from previous years. We’re just going to open it up to the panel to what your experience has been.

Karen Dorsman:

I can go ahead and start. First, thank you for the invitation. This is truly an honour. Well, I’m biased but I’m really enjoying the hybrid mode, particularly because I’m able to back to those sessions if for some reason I was not able to catch. One of the big things is that when you’re in person, you really have to decide and prioritize which session you’re going to. But that’s not the case when it’s a hybrid and you can catch it later. But, what do the others think?

Dr Maureen Okafor:

I completely agree with you. And to just thank the AAIC and Alzheimer’s Association for having me on here for this conversation. I agree with you completely, Karen. I think that just having this be one of the largest get-togethers in conferences, especially in dementia science, being one of the first organizations to plan and execute a virtual space where people in person and remote can meet together and collaborate is wonderful. I’ve had a tremendous experience so far, so it’s been great.

Alexander Ehrenberg:

One of the things that’s been really nice, actually, is in the scientific sessions, usually they stick the Q and A sessions because we’re just pressed for time. And one of the things that’s changed this year is the Q and A sessions have all been at the end, and incorporating questions from both the virtual audience and in-person audience. And I actually think that it’s given rise to better discussions.

Dr Rebecca Edelmayer:

How about you, Wagner?

Wagner Brum:

Yeah. I’m really enjoying this hybrid format. I mean, the advantage to an in-person conference, of course you can watch the content on demand later and you don’t have to worry if you miss any sessions. But I think we really got to feel a little bit a part of the conference with the whole hybrid session when we could have our questions be mixed with those of people who are actually there. So, I think it was a really great format.

Dr Rebecca Edelmayer:

How about you, Anna?

Dr Anna Volkmer:

I also wanted to add that it’s been wonderful being able to attend despite having clinical commitments during the COVID pandemic. Actually being able to fulfill my academic commitments and continue those things that I love whilst actually serving the patients that I see is a really wonderful opportunity. And I’m really grateful that the AAIC has done this online, this hybrid method again. It means that it’s feasible for us. Thank you.

Dr Rebecca Edelmayer:

I think our first discussion we want to do around biomarkers from clinical trials and clinical settings. And I think really where we want to start with is talking with Wagner and Maureen. And we know that biomarkers have been discussed at AAIC. They span from brain scans to blood tests, and have once again really been a hot topic. This week began with [inaudible 00:07:39] plenary on Monday, and is completing today with sessions focusing on how biomarkers can move from research settings into clinical practice. So, the development and optimism of biomarkers is really crucial, we think, for multiple sessions. And first, in order to approve that diagnosis, making it more timely and accurate, this is really a focus we know, Wagner, of your work. And second, in order to improve clinical trials with the appropriation of biomarkers into those trials, allowing for the assessment of the impact of the treatment on disease progression, and this is particularly a focus of Maureen’s work. So, Wagner and Maureen, would you be able to tell us a little bit more about your work and interest in this area?

Wagner Brum:

My research interest, I think I’ve been thinking about it in a broader sense, is to understand how we can use biomarkers to support better decisions. I mean, we have to make decisions all the time. In a clinical setting, we need to decide whether to see the patient or not. Or even in a research setting, once you study a disease and we might end up using biomarkers to define the root that constitutes the disease we want to study. So, I’m really curious to try to understand if we are making the best decisions to use these biomarkers. In this big biomarker theme, I think that considering what’s happening now in the field, I’m also very interested to understand how can we use more biomarkers? I mean, what biomarkers reflect, how they relate to your pathology, CSF biomarkers, and how they can ultimately be used in clinical practice for differential diagnosis against other non-AD dementias. And also, assessing the risk of future cognitive decline.

Dr Rebecca Edelmayer:

That’s great. Maureen, go ahead.

Dr Maureen Okafor:

Yeah. And my overall interest is in clinical trial design and conduct. I have a specific interest in vascular and biomarker contributors to neurodegenerative diseases, especially as it relates to Alzheimer’s disease and cognitive decline, cognitive aging. My more recent projects that I’ve done with my mentor, Dr Ihab Hajjar at Emory, focuses on repurposing drugs that look at, or at least that target different AD pathways. For instance, neuro-inflammation and the amyloid pathway. And just trying to see how we can use the knowledge and the drugs that we already have to funnel through to therapeutics for Alzheimer’s disease.

Dr Maureen Okafor:

Overall, I think I like to see how clinical trials can translate into a clinical practice and how we can use all the information and all the knowledge that we’re gaining conducting all of these trials into providing better care to patients.

Dr Rebecca Edelmayer:

Thanks, Maureen. Wagner, maybe just to follow up with you, I know that in preparation for us doing this session today you shared with us that a key question that you are on the lookout for to hopefully answer at AAIC was how close are we to new blood biomarkers in terms of them reaching clinical practice? And why is this such an important issue?

Wagner Brum:

We know that Alzheimer’s disease is the most prevalent cause of dementia, but we also know mainly from neuro path studies that Alzheimer’s disease rarely occurs alone, and several other brain diseases might be into play. I mean, considering the varied and underlying new pathologies, we really need biomarkers to understand what’s biologically going [inaudible 00:11:16] to the clinical syndrome of each patient, of the way each patient presents. If we have a patient with memory issues, 10 biomarkers tell us whether it might be something that Alzheimer’s disease might be contributing to. And of course, as we enter the new era of disease-modifying therapies it will become even more important to make sure that we are screening and pre-screening the right candidates for a disease-modifying treatment.

Wagner Brum:

And even aside the new era of disease-modifying treatment, having for instance a good differential diagnosis biomarker can be such an important tool to help physicians to make better and safer decisions. And for instance, avoiding the medications that might not be advised for a specific patient, and therefore avoid an iatrogenic cascade, which we know is so life-threatening for the elderly. So, I think that considering how relatively cheap and scalable are blood tests, they are really interesting to help us answer these questions.

Dr Rebecca Edelmayer:

Did you feel that coming to AAIC this year, that you have a better answer in how close we are to having these types of tools in the physician’s office?

Wagner Brum:

I think so, yes. And I mean, we had the new P-tau way of biomarkers in the blood last year. And I think so much has happened since then because we had different assays, different platforms, new [inaudible 00:12:53]. We have now a more deep understanding of what’s going on with these markers. But I mean, the conference more concentrated on the sessions and the challenges that we still have, so I separated. I still think that I think was important to highlight here. I think that for instance, starting with Monday, something that I think a lot of times about is what we consider about … Not only about, an AD biomarker. And I think there was a very nice session chaired by [Bill Vegas 00:13:22] and [Michael Scholl 00:13:24] on the ever-changing landscape of biomarkers. We have a very nice overview, from neuropath to imaging, to CSF and blood. And I think discussing what we understand as an AD biomarker is really crucial so we do not also limit it only to amyloid and tau biomarkers.

Wagner Brum:

And too on Monday, we had the plenary with [Henrick 00:13:47], in which … Well, I think he gave a fantastic overview of where we stand with fluid biomarkers, of what has happened in CSF, in blood, what are the challenges. I think that maybe the things, the findings that I found more important and most novel, of course regarding what we have seen in the past year, on Tuesday in the plasma session we had some fantastic data from the Mayo Clinic presented by Dr Michelle Mielke. And I mean of course, people who develop the fluid biomarker assays want to ensure the assay was working. We want to know what the assay is measuring, what it reflects. People with biomarker cohorts want to know how it relates to PET and how it can be used for prognostic assessment. But people with population-based cohorts need to provide us with that window into real-world data.

Wagner Brum:

And in specialized cohorts, we became very used to seeing very high accuracy for detecting pathology and tracking disease progression. But for instance in the Mayo data with population-based cohort, we saw that P-tau might be as increased in Alzheimer’s disease as it is in chronic kidney disease, or in patients with previous stroke or myocardial infarction. And if we are to just look at how well these P-tau isoforms is detected in this Mayo Clinic broader studies’ pathology, we see AOCs of .7, which are a bit lower than what we were used to. And I mean, I think this is all just to highlight … I think we have done amazing work, and this is just highlighting how long is the road until we get there still. And this doesn’t make these biomarkers not a little less amazing, because they are the biomarkers that are going to change the way we see Alzheimer’s disease and we can do large scale. But it’s really nice to have this real-world data.

Wagner Brum:

And still, in this plasma session on Tuesday, regarding clinical application. Sebastian Palmqvist from the BioFINDER presented some of their data that they have been doing some fantastic work both on correlations with PET and also with individualized prognostic models. We have some really interesting data, and it’s also much in line with what Dr [Oscar Hansen 00:16:09] presented today in the session. And I think it’s so nice to see that these biomarkers are performing well in specialized cohort.

Wagner Brum:

And another interesting thing, considering that last year we had blood P-tau181 and 217, this year we had another biomarker coming in to play, blood P-tau231. We also had CSF data on that, some very nice results presented by Nikash Tere from Gothenburg. And some very interesting developments to see how this biomarker can also be a very dynamic and early biomarker. Much interesting to see how it was presented in line with GFAP as a new, also, biomarker, tracking very early changes in disease. These are my main highlights from the blood side.

Dr Rebecca Edelmayer:

Wow, that’s great to hear, Wagner, because it’s really remarkable, I think, how far we’ve come with blood plasma markers, I think, moving down the pipe. And I think there’s still a little bit more time where we’re going to see these readily available at the physician’s office, but a lot of global efforts going on worldwide. So, thank you for sharing those highlights with us.

Dr Rebecca Edelmayer:

I want to pivot now to Maureen. Maureen, I’d like to ask you a question. We heard in your introduction about the range of clinical trials that you’re really involved in. What have you personally been on the lookout for while attending AAIC this year?

Dr Maureen Okafor:

Oh, goodness. There has been a tremendous amount of information just in one week. I’ve been interested in seeing how we can streamline all of the knowledge, all of these research efforts that we’re putting into ADRD clinical trial design and pathology, and how we can use all of the knowledge that we have to better predict clinical trial success in the ADRD drug discovery. And not even just that, but across the different pathways that are tested across various trials.

Dr Maureen Okafor:

I think that I was looking out to see how we could use these diagnostic criteria, these different biomarkers, PET biomarkers, CSF, the new blood-based biomarkers, how we can translate those into use in clinical settings, how patients can walk into a clinic and be able to get tested for these things. How can we possibly utilize all of these biomarkers in clinical research setting? Are we able to reduce the number of lumbar punctures that we do by increasing blood-based biomarkers within our trials? We know for a fact, at least based on some of the posters that I saw and some of the presentations, that participants do provide some negative response with respect to performing lumbar puncture procedures, and sometimes those are stopgaps to having people participate, especially within certain underrepresented populations.

Dr Maureen Okafor:

And so moving from discovering new biomarkers, to validating them, to actually deciding on cutoffs for these biomarker levels and actually utilizing them in our research and in our clinical settings I think would be wonderful and would help to fast-track the process of getting us from doing research to actually reaping the gains of all the work that everyone’s doing in this.

Dr Rebecca Edelmayer:

Why is this such an important question for us, Maureen? Why do we need to solve this at this time?

Dr Maureen Okafor:

I mean, it’s obvious. I was at one of the presentations this morning, and we were talking about how there’s a yearly upsurge in the incidents of disease burden of Alzheimer’s disease. And not just Alzheimer’s disease, but other neurodegenerative diseases. I mean, the numbers are staggering. There are 6 million individuals who are 65 years or older who have Alzheimer’s disease right now. And it’s incredible to think that in 30 years, that number is going to double. And so I think that there is an urgent need for us to maximize on the time and the resources that we have. And I think that we need to invigorate the dementia science space. And I think that if we move from thinking about this as dementia science, which is long-term, and thinking of this as something that’s life-threatening to people, to families and to loved ones, then I think that it would help to integrate the space and create at least some sort of urgency.

Dr Rebecca Edelmayer:

No, it’s great to hear that because we know there is urgency to continue to push forward for all of us, I think, Maureen. One of the things I actually was very curious about for you was in your work in this space even in just the past few years, have you seen advances and changes in trial design, where you’re incorporating more biomarkers into some of those drug development trials? That you’re seeing, that maybe are happening in your institution? And have you seen any additional advances that you’re taking away from you that you might like to incorporate from AAIC this year?

Dr Maureen Okafor:

Yes. I mean, there have definitely been advances. I think as Wagner said, there are always novel biomarkers being developed. And this is great. I think that we aren’t at the point, though, where we’re able to utilize these biomarkers, some even in research. I was excited to see a lot of the sessions with the AAIC this year talk about validation studies. So, even though we had new biomarkers this year that were presented, for instance the Monday session, the ever-changing landscape of Alzheimer’s disease biomarkers, kind of focused more on validating some of those biomarkers so that we could start to use them. I recall a session where there was discussion about who is the person, or what groups should lead the way or lead in that direction? Are the researchers the one to say, “These are the biomarkers to be used”? Or is this going to be a government-led situation? Or is this going to be one where there is some sort of a collaboration, similar to, say, the NIAAM Alzheimer’s Association Framework, the ATN?

Dr Maureen Okafor:

I think that we need to get to a point where there is some sort of collaboration and agreement on guidelines to use for biomarkers as well as cut-offs that we use not just in Alzheimer’s disease but in other neurodegenerative diseases, because we do understand that cut-offs differ based on the specific neurodegenerative disease, and sometimes even based off of different characteristics and features within a specific disease model.

Dr Maureen Okafor:

Today’s session on towards clinical application of PET was super interesting to me. I think it was a really great session to talk about how we can start to utilize tau PETs. Even though they’re expensive, but how to utilize those at least still within the research space for earlier diagnosis and treatment of Alzheimer’s disease.

Dr Maureen Okafor:

One of the speakers, I think, in this AAIC mentioned moving towards reporting quantitative AD biomarkers, and reporting those to participants, reporting those, rather than using terms like amyloid-positive, or amyloid-negative. So, these are at least the major highlights. I think that there is still a long way to go, but starting to think of ways in which we can translate the work that we currently have into our clinics, into our communities. I think that would be a good way to go just to get us moving ahead and moving forward.

Dr Rebecca Edelmayer:

Thank you, Maureen. That was fantastic to hear. And thank you, Wagner, for your updates and your highlights. I think it’s great to see all of the exciting things that you were able to catch up on at AAIC. I’m going to pass it over now to Percy so we can continue moving on.

Dr Percy Griffin:

Sure. And thank you all for your comments and talking about what you’ve seen. A lot of exciting science, but I want to pivot a little bit here because I know that an area that I think all of our panelists have an interest in today is understanding how we can address health disparities. Now, we’ve seen this discussed from multiple angles, and I know Anna is keeping a close eye on the clinical manifestations regarding how we can meet the needs of people with dementia in diverse languages and cultures. And also, Karen has been focusing on public health and dementia care regarding the latest in understanding differences in risk factors that may be drivers of health disparities.

Dr Percy Griffin:

I just want us to start with Anna here. Anna, can you tell us a little bit more about your work? What led to your interest in this area?

Dr Anna Volkmer:

Thank you, Percy. I work as a speech and language therapist in London, which is a very multicultural, as most of the world is now, very multicultural city. And I’ve been seeing people with dementia, clinically, for many, many years. Almost 20 years now. And most of those people that I see are multilingual, and yet the tools that we have available to us, the assessment tools, the psychometric tools, and the therapies, which are fairly minimal. This is a really novel area for speech and language therapists. So, the area of dementia, there isn’t a heap of research out there on the role of speech and language therapists in dementia. And what we have has mostly been developed for people who are monolingual, generally for people who are English speaking, and often from very white, middle class backgrounds. They’re the kind of tools that we’re dealing with.

Dr Anna Volkmer:

That’s the kind of research that’s been done, so when speech and language interventions have been developed, often the case studies … Because we’re really not able to do trials in this area yet. But where there has been small groups studies, they’ve often excluded people who are multilingual, who are from non-English speaking backgrounds, quite frequently. And that means that when we’re trying to plan interventions for people or plan to assess people, to diagnose their difficulties, it’s actually really tricky because we’re using tools that aren’t tailored to their needs. So, I really appreciated Maureen’s comment earlier, two of them, that actually this idea that dementia is an urgent issue that we need to consider not only for the people but for the people around that person.

Dr Anna Volkmer:

And often when I meet people, it’s the people and the places around that person who are saying, “What do we do? How do we communicate with our loved one now they have memory difficulties, cognitive difficulties, language difficulties?” And I specialize in developing interventions tailored to the needs of people mainly with language-led dementias, actually. So, dementias such as primary progressive aphasia associated with frontotemporal dementia and Alzheimer’s disease. And we’ve developed interventions that particularly try and meet the needs of people and their family members. So, we’re really looking at interventions about conversation, about quality of life and communication and social interaction. And so that’s been the main focus of my research.

Dr Anna Volkmer:

But what I’m particularly interested in from this conference is the diversity of presentations. And I’m really glad there’s been such a diverse group of professionals and academics presenting, because often researchers who focus on interventions haven’t been so prevalent at these types of conferences. There hasn’t been so much research focused on this. And I’ve really enjoyed listening to people who’ve been doing this, but also listening to people who’ve been addressing the needs of people from hard to reach and multilingual backgrounds. There have been some really great sessions that have described some really creative approaches, and I think that’s actually really key for us to think much more creatively, and think about what people need with people. So, not think about what people need because we’re the clinicians and the academics, but actually work with people to see how we can address their needs in this area.

Dr Percy Griffin:

Thank you. Thank you for those comments, Anna. One other thing I wanted to ask is at AAIC, what advances have you seen towards the assessment and interventions being optimized for people from diverse languages and cultures?

Dr Anna Volkmer:

Thank you, Percy. That’s a great question. I want to highlight two particular sessions that I felt real highlights, really important sessions. There was one on Wednesday, so novel approaches and methodological issues in study of bilingualism and Alzheimer’s and related dementias. That was chaired by Tumar Spark and Miguel Rentería, but also there was a second session on Tuesday which was around novel approaches to diagnosing cognitive impairment in diverse languages and cultures.

Dr Anna Volkmer:

I’m going to start with the first one, actually, because this session had, I think, four presenters. But there was one particular presenter I want to comment on first. Dr Stephanie Grasso, who’s a speech and language researcher who focuses on developing interventions for people with language-led dementias. And she’s probably one of the first people who has developed an intervention and treated people across two different languages. She treated people with both the atypical Alzheimer’s language-led dementias, so logopenic variant PPA and also people with semantic variant PPA, most commonly associated with the frontotemporal dementias, of course. And she treated a group of people who spoke both English and Spanish, and then also within that group there were also people who spoke other languages including Farsi and English. And she looked at whether you could train them in one language, and whether the effect of doing so, training people on words in one language, could actually translate into their other language.

Dr Anna Volkmer:

And what she found was that if you train people on target words that are cognates, so by cognates I mean words that have a similar derivation in both languages. So for example, the word in French, [foreign language 00:31:58], means purse. So, there is a very similar derivation of those two words across French and English. If you selected a set of target cognates which have similar origins, you’re more likely to see translation into both languages. And you’re actually also likely to see that carryover being maintained for up to 12 months post the intervention being delivered. So, I think it’s huge, really. Not only are we able to improve a person’s ability to name words and use words but we can also demonstrate that that carries over to their other language, and that we can maintain that for up to 12 months.

Dr Anna Volkmer:

The other person I wanted to flag in this session was Avanti Paplica, and she was talking about multilingual patients that she works with in India. And I just thought this was so powerful. She talked about their being 26% of the Indian population is bilingual, which is around 255 million people. And they speak 122 major languages, so 22 are official, but about 1,500 other languages exist. And she is a neuropsychologist, and she was looking at how you assess people with dementia who speak multiple languages like this. And they’ve come up with a set of guidelines, and I just wanted to summarize a couple of them. And one of them was that you should assess people in the most proficient language they have.

Dr Anna Volkmer:

But the second one, the second recommendation, was that the examiner should be proficient in that target language, which I think is actually … And she flagged this in her presentation. That’s often the most difficult issue that we, as the professionals or academics, don’t speak all the languages that the people that we’re working with speak, which I found quite interesting.

Dr Anna Volkmer:

The other thing I wanted to mention from the Tuesday session on novel approaches to diagnosing cognitive impairments in diverse languages and cultures was a session that really stuck with me. And having worked in Australia myself, there was a speaker talked about how to reach the really hard to reach groups in Australia, the Indigenous and Aboriginal Australian people with dementia. And what they did was this absolutely fantastic, co-produced piece of work on educating people in those groups, in those hard to reach groups, about dementia. They worked with people to co-produce artwork, so they worked with people and their carers and their family members, and they produced these incredibly moving and beautiful artworks. And they integrated those artworks into their educational materials to convey to those groups what the impact of dementia is, what dementia is at all.

Dr Anna Volkmer:

So, to support the education and support for those groups because the artworks were considered so powerful, so valuable, so much part of their community and the way they communicate with each other. And I just wanted to finish with that as a highlight because I think that the co-production work that was done there, so actually asking people in that community what would be meaningful to them, was incredibly moving. But also, the most likely to have an impact on this group. So, coming back to that comment at the beginning, I think too often that we, as academics and professionals, assume that we know best. And actually, this is just a beautiful example of how they worked with the local hard to reach communities to produce something that was helpful and meaningful to that group.

Dr Percy Griffin:

Sure. Thank you so much for that, Anna. It’s great to see all the progress we’ve made in this space, and it’s great to see that this is part of the conversation of these days. I wanted to switch really quickly to Karen. And I know your research interests span environmental and social, cultural determinants of health across the lifespan which may help explain the differences in dementia risk among different populations. What factors have been on display this AAIC that you’ve seen that have piqued your interest?

Karen Dorsman:

Yeah. I believe that this year’s session reflect how much the field is considering the heterogeneity within the populations that are impacted by ADRD, and the multidimensionality of the risk factors. The session that Dr Anna Volkmer just highlighted, that was facilitated by the bilingualism on PAI, that was a fantastic session. So, if you didn’t catch it just please go back and look at it.

Karen Dorsman:

And I think three main things stood out for me this year. First, how the effort is still on understanding ADRD in groups that have been historically marginalized from aging research, such as Alaskan Native, American Indian or transgender people. It was really good to see that we are giving appropriate attention to these groups. And ADRD research has been historically conducted on racially homogenous groups, and now we know that the risk factors differ in diverse groups, so what we know may not necessarily apply to all populations. And that’s why it’s important that we pay attention to very different factors.

Karen Dorsman:

Today’s session on diversity in clinical trials is excellent, also, highlighting this, so please go check it out. And another main theme is how we are highlighting the role of risk factors that stem from structural issues, such as environmental, racism, air pollution, discrimination, neighbour scarcity. It’s crucial for understanding. And that translational piece that would strive to improve clinical care for those of us who do clinical care and research. And I’m hopeful that in the future years, we’ll see more work incorporating an intersectionality framework. Definitely, also check out Dr [Amy Kind’s 00:39:06] plenary from Monday, because that will give you just that start for the rest of the week.

Karen Dorsman:

And third, it was very encouraging to see that researchers are thinking about individual factors, such as social engagement or education from a life course perspective. We know that health experiences are not created in late life. Since we are born, since conception, since early childhood. It’s good that we are thinking, us researchers, about the individual factors but considering them in context. If you have some time to check out the prevention sessions, particularly the non-pharmacological piece, the posters also are very, very good in that area.

Dr Percy Griffin:

Thank you for that, Karen. I think Alex agrees with you on that. But I was also wondering if you could tell us more about why this is such an important question? And we all understand that, we all know that, but we want to hear it in your words, why do you think this is a critical question to address?

Karen Dorsman:

Yes. Because we’re learning more and more that the risk for dementia is compounded throughout our lives. It’s not something that just shows up when you’re in middle age. When we understand how socioeconomic disadvantage or low education or illiteracy, discrimination, affect cognitive health throughout our lives, then that’s when we have the opportunity to create a bigger impact. We want to understand and expand the biological view that we have of ADRDs to integrate it with social determinants of health, and how the biological mechanism through which these social determinants of health are expressed. So, we would collaborate with other disciplines, like public health, and we come to spaces like this, then we can help to develop policies that contribute to equity in cognitive health from a very young age. And the earlier we can detect those risk factors, the earlier we can intervene.

Karen Dorsman:

And it is also important because we’re realizing that we need to get more representative samples in order for us to answer these questions, partnering with the community, being really, truly partners with them in developing research that actually addresses their needs, and that we are all working together. I think the efforts must be coming from all levels, and that’s why I was really also excited to see the sessions chaired by Dr [Cerise Elliot 00:42:10] and Dr [Bernard 00:42:11] regarding funding, because we want to hear from diverse voices. We want to incorporate researchers who come from minoritized backgrounds. And for that, we need funding. So, it’s important that we get the knowledge so we can start getting a better pathway, understanding this. And I think it’s going to help us to shift the narrative and to be more bold and go beyond what we have traditionally done in research.

Dr Percy Griffin:

Thank you, yes. And thank you for that. AAIC, as a global meeting, have people from all over the world reporting on lots of different research. Really, we just wanted to hear what research findings you have found the most excited by, yeah.

Karen Dorsman:

Yes. I love the sessions on global perspectives. When learning from FINGERS LatAm or the [Diane 00:43:19] trials in Latin America was very interesting. Also, really I can’t highlight enough Dr Amy Kind’s plenary on Monday, and learning the recent grant that her and her team were awarded from the neighbourhood studies. And learning also how the neighbourhood disadvantages has been utilized beyond research, and how they’ve been able to facilitate this tool so other non-researchers use it for real life and public health applications have been really exciting. So, I will highlight-

Dr Rebecca Edelmayer:

Those sound like great highlights, Karen. Thank you so much. I want to make sure we have some time for Alex to talk here about some of the basic science and pathogenesis. And those are some big words for some people who maybe are tuning in who may not be scientists, so Alex, we know your research regards a lot of selector vulnerability in neuromodulatory subcortical systems. That’s a lot of big words. I was wondering if you could explain to us what that all means.

Alexander Ehrenberg:

Yeah. It’s a lot of syllables, for sure. We actually just in this past year started a professional in this area on neuromodulatory subcortical systems. So, we started to try to get NSS to catch on so we don’t have to say so many syllables. But it’s really interesting, this set of nuclei or cells in the brain that evolved 400-plus million years ago, before mammals even existed. And what’s really interesting is in a lot of tauopathies, including Alzheimer’s disease, they’re some of the first regions to be affected. But what I spend a lot of time thinking about is the role they play in just keeping us alive. These regions, again, evolved so early on that their basic role was to just regulate sleep and your ability to become aroused in stressful situations.

Alexander Ehrenberg:

If you’re thinking about life history factors and how they’re influencing individuals, it’s a really great place to look at. And there’s reasons both stemming from evolutionary histories as well as life course histories why these regions might actually be affected. Of interest, one region called locus coeruleus that is … Some people call it the fight or flight nucleus. Has actually degenerated in PTSD as well, so it’s tightly engaged by anxiety and stressors. I’m actually really glad that I was right after Karen at this, but Karen and I used to work together. And a lot of how I think about some of these things come from her and her mentor at UCSF, Serggio Lanata. Where it’s, I think, a crime that we don’t really understand how a lot of these social and behavioral factors influence individuals biologically.

Alexander Ehrenberg:

First thing I wrote down about sessions was Dr Kind’s presentation, actually, which maybe isn’t the basic science pathogenesis track but it, for sure, I think is key for trying to understand how variation in social behavior and factors influence biology at a really tight level. And I think in a lot of public discussion, especially in the last year, about health disparities, it’s treated as kind of this ambiguous, wishy-washy thing. But it’s actually affecting biology and it’s affecting your risk for certain diseases at a really tight molecular level. So, my research is focused on that, specifically in these regions that are so involved with just how you experience the world around you.

Alexander Ehrenberg:

When these regions die off, it’s not necessarily affecting things like cognition. However, there were some nice talks at AAIC about how they do affect cognition. But some of the early signs of degeneration are things like anxiety, depression, sleep dysfunction. I’ve been really encouraged that there’s been more focus on those things, because they are a part of the disease process. It’s not some ethereal thing, but I think sometimes it’s talked about in that context. Hopefully, yeah. In lay terms, that’s a lot of what I focus on. And I just really think it’s important that we get at the underlying mechanisms for some of these things.

Alexander Ehrenberg:

Of course, non-pharmaceutical interventions are a great way to deal with them too. I think if we can actually understand it’s a great, economically advantaged way to address disease, because it might just be things like helping improve access to resources in neighbourhoods that we maybe could identify through some of the tools that Dr Kind talked about in that amazing plenary.

Dr Rebecca Edelmayer:

Alex, I think you hit upon some of the important reasons why we really need to study this. And I’m gathering from what you just said, it’s not only going to potentially impact people living with dementia but also their caregivers because of quality of life, and even that responsibility through giving could be relieved a bit would have … What stood out to you at AAIC that you were most excited about?

Alexander Ehrenberg:

Yeah, I mean this, I think, is my sixth or seventh AAIC. And the first one I was at, there was, like, two posters on degeneration in the locus coeruleus, one of which was mine. And now, it’s like there’s so many cool ones, and there’s so many people thinking about these issues. I mean, if you’re looking through the poster session, just look for stuff on the locus coeruleus and hypothalamus. There’s stuff about post-mortem series and evaluating how early these regions are degenerating. There’s been really cool biomarkers recently. We’re now getting better and better and measuring things like the locus coeruleus in vivo, which wasn’t really possible until a while ago. But there are a number of groups working on that, so I would encourage anyone to just look through these sessions. And it’s ranging from people thinking about psychiatric symptoms, through biomarkers, through basic science and neuropathology.

Alexander Ehrenberg:

There was also another talk yesterday, or session chaired by Mark Hammond. I mean, it wasn’t actually really about the neuromodulatory subcortical system, but it was about advanced in single-cell omics approaches, which is really a new world that I think basic scientists are starting to wrap our heads around. The plenary on it, there’s a bunch of posters on it. And what’s really exciting about that is that there’s a lot of heterogeneity in the brain. And that heterogeneity underlies selective vulnerability, but we haven’t really had a great way to investigate on a cell by cell basis, especially in humans, until really the past couple of years. And for me, studying these early subcortical systems, we want to know why those cells are the ones to die off early on. And I’m just really excited I have tools to look at that now.

Alexander Ehrenberg:

Actually right now, there’s another session happening, a talk that’s co-chaired by Dr [Lake Ember 00:51:04], Dr [Heidi Jacobs 00:51:05], who chairs for our executive committee for that professional interest area. And it’s looking at how degeneration in neurological systems, specifically [inaudible 00:51:17] impact of amyloid deposition. There is several papers and animal literature that actually show that not only are there behavioral effects of degeneration of [inaudible 00:51:29], but it affects underlying neurophysiology in a way that makes the rest of the brain more vulnerable to disease. And now, we have great work that is starting to look at that.

Alexander Ehrenberg:

So, right after this session I’m probably going to go and look at that on demand, and then I would encourage people to do that with me because I really want to hear their thoughts. And then the last thing I’ll mention too is the main symptoms that at least I conceptually relate to degeneration of those patients are neuropsychiatric symptoms. And there was a couple of great talks yesterday about both treatment and diagnostic criteria for those that, I think, become really important if we’re trying to longitudinally evaluate patient populations in a way that allows us to get at some of those behavioral symptoms that actually might be manifestations of the same disease process as would be causing memory issues, just in a different region that would instead maybe cause depression. And we need to be a little bit more sensitive to some of those changes. So, I really loved those talks as well. They weren’t really talking about molecular biology or anything like that but it’s, I think, super informative for people who are thinking about molecular biology to understand that psychiatric and social behavioral perspective.

Dr Rebecca Edelmayer:

That’s right.

Dr Percy Griffin:

Thank you. Thanks for that.

Dr Rebecca Edelmayer:

I mean, I think it was like we’ve gone through so much. I think I’ve also heard each one of you maybe put a plug in for each one of your professional interest areas as you’ve been talking along here, and maybe we’ll do one last, rapid round question for each of you. It’ll be a test for you and your executive planning, maybe. I’ll let Percy give the last question for the day.

Dr Percy Griffin:

Yeah. As Rebecca mentioned, sounds like you’re all ISTAART members, you’re all part of professional organizations. So, how do you all plan to continue these discussions year-round? Because AAIC is, what? Five, six days. However long it is. But we need to have these conversations more, so what are your plans for that? And really quickly, because we’re almost running out of time. Just reflect. We could start with Wagner.

Wagner Brum:

Yeah, yeah. Of course, I’m ready. And I planned it better than my previous talk. I’ll be faster now. But I’m going to do some promo for the PIA I’m most involved in right now. There’s a new PIA called the Professional Interest Area, Celebrate Early Career Researcher. The whole goal of the PIA is to connect early career researchers throughout the year and try to maintain this networking conference atmosphere the whole year long. And pretty soon, we’ll have a global survey out to understand what are the challenges of ECRs in dementia science around the world. So, join ISTAART, join the ECR PIA, and answer the survey that will be out very soon.

Dr Percy Griffin:

For sure. Thank you, Wagner. I think we’ll move to Anna next.

Dr Anna Volkmer:

Thank you. I’m just going to echo what Wagner said, actually. I’m going to try and invite more speech and language therapy clinical academics and speech and language researchers to join ISTAART so that we can have more presence at these type of events. Because I think we could really helpfully collaborate with other professionals that way, the more of us there are, that then that helps us work together to move this field forward.

Dr Percy Griffin:

Thank you. And I’m going to throw a curve ball and ask Alex now.

Alexander Ehrenberg:

Yeah. Also, I’m a co-student chair for the neuromodulatory subcortical systems PIA, NSS PIA. One of the lovely features of that PIA is it’s very multi-disciplinary, so we have people working on biomarkers, neuropsychologists, basic scientists, and we’re starting to plan out a series of webinars on even things like basic neuroanatomy of the region. We’re going to try to collaborate with ISTAART leadership and the Alzheimer’s Association to put together those educational materials. And maybe even make them accessible to young, K through 12 students who are interested in the brain. And we’ll probably emphasize the role of neurodegenerative diseases in the region as well, but I think it’s just valuable to create educational resources for that. We have the experts in our field.

Dr Percy Griffin:

Can we hear from Maureen?

Dr Maureen Okafor:

Yes, of course. I’m going to just follow with Wagner and shamelessly plug in for the CTAM PIA. I’m a member of the executive committee for the CTAM PIA, and it’s the clinical trials advancements and methods. And even though AAIC is going to be ending today, there is going to be a lot more sessions and a lot more educational gatherings and webinars in the coming weeks. So, starting off with a session that we’re going to be having. It’s an educational workshop called … And we’ll be presenting perspectives on adaptive trials and future trial design. This is on August the 11th, I think, and it’s at nine o’clock in the morning, Eastern Standard Time, I think. And we’re also going to be having the CTAM PIA scientific session and business meeting, September the 8th. And we’re going to be presenting I think two topics, just focused on remote assessments in clinical trials, especially now that a lot of participants are … We’re kind of being innovative in how we collect clinical trial data in this setting.

Dr Maureen Okafor:

The CTAM PIA has recently started a journal club, and so we’ll be trying to do those two or three times in a year. So, we’re having early career researchers who are interested in presenting journal works, articles. You can reach out to me, just search for Maureen Okafor on the AAIC website.

Dr Percy Griffin:

Sure. Thank you. And finally, Karen?

Karen Dorsman:

I think, like my colleagues said, join the PIA. I’m part of the diversity and disparity, and I sometimes join the bilingualism PIA. I mean, they’re fantastic. You can get that interdisciplinary collaboration. Another way is if you are on Twitter, join the academic Twitter world and always have these conversations over tweets. It also helps synthesize information, so that has been really helpful. Give back, right? As researchers, we want to give back and we want to connect and really hear from the communities that we serve and we work with so we can help those conversations at all levels, with our colleagues, with the communities, and all of this global community.

Dr Rebecca Edelmayer:

That was amazing, Karen. Thanks for that ending. I think you said it better than Percy or I could. I think keep connecting with each other, keep connecting with your communities. I want to just, myself, I think on behalf of the association and on behalf of Percy, I want to thank all of you for joining us today. This has been an amazing session. This is the first time we’ve done this before, and I just want to say it’s been great and we plan to continue to try to create these opportunities in the future because it’s so wonderful to hear from you all what you’ve found more intriguing at AAIC and what you’re going to try to push forward for the future. So, thank you so much for attending. Thank you to all online, and we hope to see you next year at AAIC. Bye-bye.

Dr Percy Griffin:

Bye-bye.

Adam Smith (Introduction / Voice Over):

Thank you very much for listening. I hope you enjoyed that just as much as we did. What fantastic insights into their own work, and the sessions they’ve seen across the week. Thank you very much to the Alzheimer’s Association for very kindly sharing the recording with us and giving us permission to share it with you. Remember, you can still access the conference content for 30 days at Alz.org/AAIC.