COVID-19 and Its Effects on the Brain

Transcript

Intro: I’m Dr. Nathaniel Chin, and you’re listening to Dementia Matters, a podcast about Alzheimer's disease. Dementia Matters is a production of the Wisconsin Alzheimer's Disease Research Center. Our goal is to educate listeners on the latest news in Alzheimer's disease research and caregiver strategies. Thanks for joining us.

Dr. Nathaniel Chin: Welcome back to another episode of Dementia Matters’ special series previewing the 2022 Alzheimer’s Association International Conference, where we’re getting to know some of the conference presenters before the event starts on July 31st. If you’re interested in hearing more from the conference and the research being discussed, the AAIC is opening the plenary sessions to the public for free with registration. Register for these free talks before this Sunday at aaic.alz.org or at the link in the episode description. More than two years after the start of the pandemic, there is still so much we don’t know about COVID-19’s effects on the body. Recent studies have shown that 1 in 5 U.S. adults who were diagnosed with COVID-19 now deal with Long COVID, a condition where individuals report fatigue, cognitive issues, difficulty breathing, and other symptoms lasting at least three months after infection. With these reported effects on cognition and brain health, what else do we know about COVID’s impact on the brain? Joining us today is Dr. Heather Snyder, vice president of medical and scientific relations at the Alzheimer’s Association. Dr. Snyder will be leading a scientific session at AAIC called COVID-19 and the Brain: Data from Ongoing Studies Aimed to Better Understand the Neurological Sequelae on July 31. Welcome to Dementia Matters, Dr. Snyder.

Dr. Heather Snyder: Oh, thanks so much for having me.

Chin: So, Heather, how did you first get involved in the Alzheimer's Association and what's your role there?

Snyder: Yeah, great question. I joined the association a little over ten years ago on the science team. I came to the association really to work with Dr Maria Carrillo, our chief science officer, on our funding programs and the different ways that the Alzheimer's Association funds research. We have significantly increased our funding over the last several years and really diversified – continue to diversify our portfolio, the types of programs that we offer, increase the number of offerings in a given year. Today, we remain the world's largest funder of Alzheimer's and dementia science and we're funding nearly a thousand projects in 48 countries.

Chin: Well, that's incredible and the field is so large that we need that funding in order to really investigate all the many different things that can affect cognition, as well as Alzheimer's disease. So thank you for the work that you're doing on that.

Snyder: Well yeah, and I may just even comment that it's Alzheimer's and all dementia that we really look to support because of the intersection of so much of the underlying biology. I think we'll talk a little bit about that here today.

Chin: Well, I mean that's a perfect segue. There's so many different things that can affect the brain and that people are investigating. What drew you to understanding COVID-19 and the brain?

Snyder: Really at the very early days of the pandemic, in March of 2020, some of our collaborators and colleagues at the University of Texas–San Antonio – Dr, Sudha Seshadri and Dr. Gabriel De Erausquin – reached out and said that they were starting to bring together researchers that were looking at this linkage. Dr. De Erausquin had been doing some work over his career in trying to understand the impact of past pandemics, as well as looking at influenza and its influence or impact on the brain. I think that loss of taste and smell suggested that there could be a linkage, at least in the underlying biology, and so wanted to start thinking about that and asking those questions. That group really continued to meet and continues to meet today. It's the COVID-19 Consortium or Network. The Alzheimer's Association continues to support and bring that group together with the team at University of Texas–San Antonio.

Chin: So what do we know so far about COVID-19 and its impact on the brain and thinking ability?

Snyder: You know, the science is still emerging all of the time, but I do think we've seen this association of some individuals that do experience this memory changes, changes in their cognition, their thinking, their reasoning, for a prolonged period of time after COVID-19. But when we look at some of the underlying biology, we also see that some individuals have immune changes or certain kinds of Immune responses. Other individuals, we see changes in their blood-brain barrier, that barrier that protects their brain or protects our brains. Those biologies are also some of the changes that we see in individuals with Alzheimer's, so trying to understand or relate those biologies as what they may mean for long-term impact becomes a really important question. We also saw in some of the population data the comorbidities that we see in Alzheimer's and other dementia were some of the same comorbidities that were increasing an individual's risk for complications related to COVID-19. Looking at all of that, the umbrella of all of that together, it did suggest that we needed to be asking these questions and trying to understand what the linkage may be, if anything.

Chin: And you draw a very interesting similarity because in COVID-19 a person can lose their sense of smell and taste, but in neurodegenerative diseases you can also lose your sense of smell and taste. Why is that such a prominent feature? What is it about our sense of smell that is meaningful to the brain?

Snyder: I think, I mean, if you think about our brains, our brains are responsible. It's the control center – right? – of everything that we do including tasting and smelling. In Alzheimer's, as the disease continues to press, I mean it is a fatal disease and ultimately even the ability of remembering how to swallow, what food tastes like – those are things that get lost as the disease progresses.

Chin: Has the impact changed as the COVID-19 virus has changed or as vaccinations have been introduced to the population?

Snyder: Great question, and certainly something that folks are asking right now. Looking at the data, I mean I think, as the variants change and there are new variants, what are their potential impact on the brain, individuals that perhaps are vaccinated with a certain type of vaccine versus another, what does that look like? Those are questions that are being looked at but we just don't have the information yet.

Chin: It's interesting because things are just so early in this. This is such a novel process that has really challenged science and researchers. I think it's hard for people to hear that we just don't know yet, but that is the point of science – to investigate these new things that may be impacting something that's been around for a long time, like Alzheimer's Disease or dementia.

Snyder: Yeah, I mean, I think there have been hints in the literature particularly there was a large study that came out of NYU that looked at individuals that had been hospitalized in the ICU, comparing those that had the continued memory changes or changes in their cognition compared to those that did not. They saw that those individuals that had the memory changes actually also had some of the biomarkers, some of those biological changes that were associated with Alzheimer's, but we don't know the before. So we don't know, did these individuals already have underlying biology that was changed before and this exacerbated it, or that we're just detecting it now. I think there's a lot of questions that remain. It is to your point – exactly, that's what science is. That's what discussion is. I mean, I’m personally really excited and looking forward to AAIC this year, that dialogue and that discussion, that sharing of information. The COVID Consortium, this network of individuals that we bring together, that's really the goal. It's sharing information. It's sharing learning. It's sharing how we collect information so that we really can do some of these shared analyses and say what is that impact in this population, in this age. We're just scratching the surface, but it is very clear that there are important questions that we've got to be asking.

Chin: Can you explain to our listeners what exactly is long COVID and how does it relate to things like brain fog that you hear people describe?

Snyder: Yeah, I mean, I think long COVID is is really an encompassing term, at least it seems to be as it emerges, that is not just changes in cognition but there are individuals that have changes in cardiovascular function, pulmonary function and on other overall biologies or functions that – systems’ functions that we're seeing change and that's all encompass within that long COVID. The brain fog that people are referring to or that we hear people refer to, that's really that changes in memory that individuals – or changes in cognition that individuals are experiencing, persistent change that is measurable. And so I think the exact definition of what defines that “brain fog”, that's still a big question, but this report of individuals, that's measurable in seeing this change I think is something that we saw last year at AAIC and we'll see some new data coming out this year as well.

Chin: Based on what we know so far, is there any relationship between COVID-19 and the actual pathology the brain changes of Alzheimer's disease?

Snyder: There have been a couple groups that have looked at this association. I think a lot of it ties to the immune response and to the immune related changes that we see in individuals, that their COVID response and how their immune system is changing, how that seems to influence some of the downstream biology. That seems to be some of the links in the underlying mechanistic association between the two, although there's still a lot of questions that we don't know and that we need to understand.

Chin: And now going from cells to much bigger human beings.

Snyder: Well yeah, and the complex of the vasculature and the systems of how all of that fits in, because we do know that COVID-19, there were some impacts in some of the vascular changes. We know that that's also important, so how that ties in with the underlying immune response somehow and the models that we should be using. I think there's a lot of questions but we're making headway in trying to ask those questions and look at different models and understand some of those associations at least.

Chin: And why do people with Alzheimer's disease or other forms of dementia, why do they get COVID-19 at higher rates or die from it at higher rates?

Snyder: Yeah, so I mean there've been a couple studies that have looked at, particularly, claims data and have suggested and have seen this increased association that individuals with dementia were more likely to contract COVID-19 and have the complications including death than individuals without dementia. There is a big question as to why, and if that's biological or if that is situational. I don't know that we know. Particularly in some of those early  early months, we did see an increase in terms of residential care and in different types of community living situations where you may see an increased number of individuals that were living in close proximity together where we saw higher rates of risk of mortality-related outcomes. So whether – if that is the reason or if it's something related to the underlying biology, I think we don't know yet.

Chin: And I'll say that the Alzheimer's Association 2022 Annual Report – which is a fantastic document, very long and lengthy, well researched – they have a very nice section on COVID-19 and mortality rates and potential reasons as to why or at least what the numbers show. And again, it’s so early in this process to truly understand but clearly there's some sort of signal. It's just a matter of figuring out what. I feel like a lot of our conversation so far is really asking a lot of questions that need to be better understood in research. So my next question for you is what does the research community need to do to better understand COVID-19 and cognition and what are the areas that we should be focusing on?

Snyder: Yeah, I mean I think we've highlighted a few of them already. It's what's the mechanistic relationship that might be associated. Is there kind of that synergistic relationship if individuals are already having some of those underlying biologies or the underpinnings that we see in Alzheimer's? Is that exacerbated with COVID-19? Trying to understand that from a timing relationship in an individual as well, but also I think going even more deeper is, why does somebody have the type of response that they may have? What does that do in terms of impacting their risk or or impacting some of the underlying biology as well at that time? Is that just in that moment? Is that reversible? Does that change? Does that impact risk? And then looking at some of the population data, as well, and trying to understand is there genetic factors that may be a play? Do we see differences in underlying genetic risk factors or genes that are associated with increased risk in Alzheimer's? Do we see changes in outcomes related to the presence and absence of those given genes or those risk genes? So those are, I think, just some of the questions but then I would underscore for anybody that is going through or experiencing long COVID, in particular with some of the changes in memory and function, having interventions and understanding what might be interventions that may also help or benefit those individuals is also an incredibly important area.

Chin: Now I don't want you to have to steal your thunder for your actual session, but if you could share with us some of the key highlights from your scientific session that will be on July 31st?

Snyder: I think what we look forward to seeing this year is looking at the studies that have continued to follow individuals or asking some of the new questions. I think we'll see, hopefully, some of that data being presented at AAIC at the COVID-19 and The Brain session on Sunday. I think it's Sunday afternoon – mid-morning, as well.

Chin: Do you think COVID-19 and its impact on cognition, will this open up more research into understanding infections in brain health?

Snyder: Yeah that's a great point and, you know, I do think the pandemic is an unwelcome link or opportunity to look at that association. There have been studies that have suggested or looked at different viruses and looked at different infections. There are implications and what they may mean in terms of impacting a person's risk. They've been very difficult to really study in terms of going beyond an association and look at any sort of cause and effect, if there is any. The pandemic has offered that type of window – again certainly an unwelcome one – but that if we have an opportunity to ask these questions now as we're in this moment. I think that's really what the Alzheimer's Association's Consortium was poised to do. It's come together. We created a common way of collecting data and information and following individuals over time and how you adapt that into your community or into your situation, in your country, around the world, with the opportunity to come back and share data to hopefully get us further in being able to ask and answer some of those questions.

Chin: Well, to end, what other scientific sessions or plenary presentations are you looking forward to specifically at AAIC 2022?

Snyder: Oh, there's so much that’s going to be throughout the entire week. I know there's a session that's looking at Multicomponent Lifestyle Interventions, behavioral interventions, thinking about risk reduction strategies. I think it’s on Monday afternoon that I'm really looking forward to. There's a session on Sunday morning that's really looking at some of the neuroimmune mechanisms and thinking about one of kind of that cell to cell, very specific mechanism of the immune biology and trying to understand what that might mean and also how that can translate into thinking about diagnosis or detection or different biomarkers. So those are two that I'm looking forward to, but I'm also really looking forward to some of the equity and health disparity sessions that I think are on Monday and Tuesday in particular. Some of the plenary speakers and, of course, hearing Dr. Francisco Lopera this week will be really exciting. I always learn so much from listening to him.

Chin: Well with that, thank you, Dr. Heather Snyder for being on this Dementia Matters special series with AAIC 2022. I certainly hope to have you on in the future.

Snyder: Absolutely! Thank you so much for having us and maybe we can touch base after AAIC and the different things that have come out of the meeting. Thank you.

Outro: Thanks for listening to Dementia Matters. Be sure to follow us on Apple Podcasts, Spotify, Google Podcasts, or wherever you get your podcasts to be notified about upcoming episodes. You can also listen to our show by asking your smart speaker to play the Dementia Matters podcast. And please rate us on your favorite podcast app -- it helps other people find our show and lets us know how we are doing. Dementia Matters is brought to you by the Wisconsin Alzheimer's Disease Research Center. The Wisconsin Alzheimer's Disease Research Center combines academic, clinical, and research expertise from the University of Wisconsin School of Medicine and Public Health and the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. It receives funding from private university, state, and national sources, including a grant from the National Institutes of Health for Alzheimer's Disease Centers. This episode of Dementia Matters was produced by Rebecca Wasieleski and edited by Caoilfhinn Rauwerdink. Our musical jingle is "Cases to Rest" by Blue Dot Sessions. To learn more about the Wisconsin Alzheimer's Disease Research Center and Dementia Matters, check out our website at adrc.wisc.edu. You can also follow our Facebook page at Wisconsin Alzheimer’s Disease Research Center and our Twitter @wisconsinadrc. If you have any questions or comments, email us at dementiamatters@medicine.wisc.edu. Thanks for listening.