Bird flu update; research into brain-related disorders: Upstate Medical University's HealthLink on Air for Sunday, Feb. 23, 2025

Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," an infectious disease doctor explains how concerned we should be about bird flu.

Elizabeth Asiago-Reddy, MD: ... We're in a place right now where we definitely need to be concerned, but we don't have, right now, an immediate threat to human health. ...

Host Amber Smith: A neuroscientist explores what brain connectivity reveals about dementia and other disorders.

Christopher Gaiteri, PhD: ... These are the points of contact between two cells. And so that's like a very important part in the brain because the brain's all about communication. And so we're studying the exact point where two cells meet when we study these dendritic spines. ...

And an exercise physiologist goes over the best exercises for seniors. All that, plus a visit from The Healing Muse, coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith. On this week's show, we'll explore what brain connectivity teaches us about dementia and other brain disorders. Then an exercise physiologist goes over the best exercises for seniors. But first, an update on bird flu.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." We've heard about bird flu in the news lately. So I'm checking in with Upstate's chief of an infectious disease for what's important to know about this virus. Dr. Elizabeth Asiago-Reddy is also an associate professor of medicine at Upstate.

Welcome back to "HealthLink on Air," Dr. Asiago-Reddy.

Elizabeth Asiago-Reddy, MD: Great to be here, Amber. Thank you.

Host Amber Smith: My overarching question is, how concerned do we need to be about bird flu?

Elizabeth Asiago-Reddy, MD: I think we're in a place right now where we definitely need to be concerned, but we don't have, right now, an immediate threat to human health. So I think an appropriate level of concern is occurring in terms of investigating what's going on in animals and trying to make sure that it doesn't impact humans.

Host Amber Smith: I know that we're sort of in the middle of the traditional influenza season. Are we testing people to see if it's influenza or if it might be bird flu?

Elizabeth Asiago-Reddy, MD: Yes. The way things are working right now -- and to a certain extent, it depends on which type of influenza test you take -- bird flu, it will test positive as an influenza A virus. And if you test at Upstate, for example, this will actually subtype the virus right away to let us know which influenza A virus it is.

If it is indeterminate, meaning that it's not one of the human influenza A viruses that we expect to see circulating, it will be sent to the New York State Wadsworth Laboratory for more detailed investigation. And at that point, they could determine if it was an avian influenza.

Host Amber Smith: But at this point it mostly infects wild birds, or caged birds, or...?

Elizabeth Asiago-Reddy, MD: It is impacting all sorts of birds at this point. So wild birds, by far and away, are the largest reservoir because we're not able to control them, and they are circulating across the globe. So they are really the reason why we have this ongoing situation with influenza on an annual basis anyway.

But the poultry and backyard flocks are being impacted by this because, of course, they come into contact with wild birds.

Host Amber Smith: What about other animals? I've heard of dairy cows and cats, right?

Elizabeth Asiago-Reddy, MD: Yeah, so dairy cows are really the biggest one that stand out. And this is something that's new. We haven't seen this level of infection in dairy cows in the past.

What we have seen in the past, and what's more typical, has been infection in pigs. You may remember swine flu from about 10 years ago or so. Pigs, we know for a long time they have certain receptors in their lung system that make them more susceptible to influenza viruses. And we didn't expect this quite as much in dairy animals.

So we're still figuring out why is this happening? Is there something about the virus that has changed that has made it more likely to infect dairy cows? And what does this mean moving forward? But what we have seen since last spring, spring of 2024, is that there has been a multi-state outbreak of an avian type of influenza virus.

So this is an H5N1 virus -- that's our typical avian influenza virus -- in dairy cattle. And multiple herds of dairy cattle have been impacted, and especially in California, but all across the Western United States in particular.

Host Amber Smith: I've heard of poultry and duck farms recently that had to euthanize all of their chickens and ducks because of bird flu. Are they having to euthanize cattle on dairy farms?

Elizabeth Asiago-Reddy, MD: They typically have not had to euthanize the cattle. But there is a lot of difficult management that needs to go on because these cattle now need to be separated from others so that they're not impacting the other cattle. So, bird flu among birds tend to spread almost immediately so that all members of the flock are immediately impacted.

The dairy cattle, there's been some cases where you can separate certain members of the herd out, so the herd, the entire herd, is not necessarily impacted, but it is significantly resulting in reduced milk production and listlessness, low energy, in the dairy cattle that are impacted. So it's having very significant economic impacts on those herds.

Host Amber Smith: Now what about cats? Do we know how the cats have gotten bird flu?

Elizabeth Asiago-Reddy, MD: Presumably by the same mechanism, although it has not been such a widespread problem to date, and especially, I think, because cats are more, they're not grouped together, so they may have sporadic interactions with birds, but we don't have herds of cats for the most part. So the potential for spread widely among cats, is much lower.

And so when a poultry farm has to cull all of their chickens, is that effective? Are they able to stop the flu that way? It is effective, but as you can imagine, it's very significant. You lose the entire flock of animals. So, it's very problematic. And in addition to the flock itself, nearby flocks also need to be assessed. So if you have farms that are next door, or down the road, et cetera, those also need to be tested and then made sure that it hasn't impacted them as well. And so it takes, this is obviously one of the things that we're seeing in terms of egg prices and reduced availability of eggs is the fact that entire flocks have had to be culled because of this avian influenza.

Host Amber Smith: This is Upstate's "Health link on Air" with your host, Amber Smith. I'm talking with Upstate infectious disease chief Dr. Elizabeth Asiago-Reddy about bird flu.

So how similar is bird flu, or different, is it from traditional influenza?

Elizabeth Asiago-Reddy, MD: What is the most important that makes it different is that it, right now, even though it has a limited capacity to infect humans, it has not developed the capacity to spread from one human to another.

So that is where we end up in a pandemic, or at least an epidemic situation, is when a person can become infected with an influenza virus and pass it on to another person. So avian influenza, as it stands right now, people who have very close contact either with a dairy cattle or with birds that are sick with this virus, can become infected. But they cannot pass -- as we've seen so far, and this is where we need to monitor closely -- they cannot pass it on to another person, even in their household, et cetera. So it strictly has evolved to infect and to be passed between the animals that we're seeing it infect at this point.

Otherwise, when we're talking about symptoms, these can be highly variable. So right now, there are a small number of cases. There have been about 50 cases that have been transmitted in the last year from dairy cattle to humans. Those cases have involved actually fairly mild symptoms, more on average milder than what we see from your typical influenza A that's circulating right now. So it's kind of flu-like symptoms, with feverish, kind of malaise, that type of thing. Actually, a number of these people have not even had fever. They've had congestion without fever, conjunctivitis, which is redness of the eyes, has been a prime feature of this particular strain of virus.

Now, there is another version of the H5N1 avian influenza virus that has recently been detected in a dairy herd in Nevada. That is a slightly different version than what we were seeing all throughout last year. And that version is responsible for the deaths of individuals. There was a woman in Louisiana who had a small backyard flock and who cared for a sick bird, and she ended up passing away. She was older than 65 years old. I don't have other details about her health history. And there was also a teenager in Canada who was impacted by bird flu who became very severely ill and required intensive care but has fully recovered.

Those two individuals both had this different strain of h5N1 than what we've been seeing throughout the rest of the year. That has happened this year, in 2025. So we are definitely keeping our eyes on that because even though we haven't seen a demonstration that that virus can be passed from person to person, the level of symptoms was more severe than with the one that we were seeing throughout 2024.

Host Amber Smith: And the seasonal flu vaccine that we got in the fall, that doesn't work against bird flu?

Elizabeth Asiago-Reddy, MD: Not specifically. I mean, there may be some degree of benefit, but it's not specifically targeted against these types. And the reason for that is because, the way that the vaccines are designed is on the hemagglutinin and neuraminidase proteins. And so that's what the H and the N stand for. Those are proteins within the influenza virus that are responsible for causing a lot of what makes you sick when you get the flu.

And so vaccines are designed to target the specific combination of hemagglutinin and neuraminidase that we expect to see in human influenza from year to year. So currently the vaccines that we have are protecting against H1N1 and H3N2, as well as an influenza B. So you can see there's some crossover there with the H5N1, but it's not a perfect match for H5N1. And you know, there would be no reason right now to do widespread vaccination of people against avian influenza because we're not seeing it in a widespread way in humans.

Because of the way these vaccines are made, the potential exists to make a vaccine relatively quickly, because we know the basic process of putting together a vaccine that involves these types of components.

Host Amber Smith: Well, let me ask you, because we're heading towards spring anyway, any advice for whether it's safe to have bird feeders in your backyard?

Elizabeth Asiago-Reddy, MD: So far the CDC (Centers for Disease Control and Prevention) has not recommended against bird feeders. And part of that is because bird feeders tend to attract a diverse array of birds, and they don't often actually reside in the bird feeder. So yes, they're potentially interacting with each other, but they're not actually living together. And so it doesn't seem like it's a very significant risk for, let's say, concentrating an epidemic of bird flu.

Also the general recommendation across the board is don't pick up dead birds that you see lying around, whether they were part of your own backyard flock or they were at your bird feeder, et cetera. That is a critical and pretty easy way of protecting yourself. Obviously if it's a wild bird, you're probably going to just ignore it or move it out of the way if you need to. If it's a member of a flock that you're raising, so let's say you have backyard chickens, and you, if that's the case, then you can actually Google. There are numbers where you should call to try to get assessed. So you can call your veterinarian. That's step one if you're not sure where else to call. And then from there they'll direct you toward testing and seeing whether there is actually a danger to the entire flock.

Host Amber Smith: Now, what about eating eggs? Is it safe to eat eggs from grocery stores or from farmer's markets?

Elizabeth Asiago-Reddy, MD: As we've seen thus far, it is safe to eat eggs, but that's why we cook eggs. OK, so, we should not be eating raw eggs across the board, period, for a number of different reasons, this being one of them. The virus is unlikely to really concentrate itself on eggs anyway. It would really have to be like a very fresh, raw egg for us to be able to get influenza virus from it because it would be expected to be on the outer surface of the egg. So eggs, no. The way that we're eating them, it's not really a concern.

Chicken, eating chickens that have been immediately slaughtered, that is really the potential risk that could occur. So people who are slaughtering their own chickens, buying chickens that are fresh slaughtered, then you want to take care to make sure you're washing all surfaces, washing your hands, fully cooking the chicken before you're eating it, and not consuming raw parts of the chicken or, particularly, chicken blood.

Host Amber Smith: What about raw milk?

Elizabeth Asiago-Reddy, MD: I'm glad you asked that question, because this has been a source of questions back and forth. I think there was recently a pretty big publication of lay press talking about some of the potential benefits associated with drinking raw milk. But the reality is, is that raw milk is a danger in this situation. This is definitely one of the reasons why we would recommend against drinking raw milk, amongst the potential for other pathogens as well, but absolutely this can be transmitted in raw milk.

Host Amber Smith: Now what about people who work on dairy or poultry farms? Are there any protective measures they should be or could be taking to protect themselves?

Elizabeth Asiago-Reddy, MD: Yes, and there are a lot of details on CDC websites that are available to review how to take care of yourself depending on the situation that you're in. So certainly your boss should be explaining what are the necessary steps based on the situation at hand.

If there has been any identification within a flock, then people are recommended to wear specific types of personal protective equipment to keep themselves safe, or the same thing if there has been recognition within a dairy herd. So that depends on what the recognition has been, what your specific role is in terms of how you interact with the animals, and again, all of this is available through the CDC as well as several agricultural organizations, on how to protect yourself and what would be recommended.

Host Amber Smith: How could this become more of a concern?

Elizabeth Asiago-Reddy, MD: So the concern that exists is that now that dairy herds have been exposed to this over a long period of time, the longer that this is living in any group of animals, the more likely it is that it could mutate, right?

That's just the same way it is with any kind of virus. So if we have more and more dairy herds that are impacted, and especially if we see sort of recirculation of the virus, like one of the things that's concerning is that this new version that made those two people so sick has been detected in cows who have already been exposed to the other version. So that's nerve wracking because it allows for the possibility of recombination and creation of new viruses that have new mechanisms of transmission. So all it has to do is take a step that allows a new mechanism of transmission that would allow it to transmit from human to human, and that's where we're in big trouble.

The more time it has circulating around in any given population, the more likely it is that something like that could happen. So that's what happened with swine flu, is that for whatever reason, the right combination occurred, and it was able to not only go from pigs to humans, but now from human to human.

I agree that we have reason to be concerned based on these dairy herds and what's happening. But we just don't know. It could be any random moment. And the way you can contrast it is influenza B. So influenza B only infects humans, and we see less illness, less change in illness for influenza B, and no real worldwide pandemics of influenza B because it's just a stable presence within the human population. It doesn't have as much opportunity to mutate as it does with an animal reservoir.

Host Amber Smith: Interesting. What about, is there seasonality to bird flu? Will things change or get better in the summer, in the warmer months, or not?

Elizabeth Asiago-Reddy, MD: Yes, there is seasonality, and all of the human flu that -- we think ultimately this probably all came from birds in the beginning, right? -- but yes, there is seasonality in terms of when things are worse. But that's the other thing that's concerning about the dairy herds, is that they've been perennially infected, because this hasn't really gone away since it was first identified about a year ago.

So the concern is, has this become endemic in some dairy herds, and what does that mean about the ability for it to mutate over time?

Host Amber Smith: Well, this has been very informative, and I appreciate you making time for this interview, Dr. Asiago-Reddy.

Elizabeth Asiago-Reddy, MD: Yes. Thank you very much.

Host Amber Smith: My guest has been Dr. Elizabeth Asiago-Reddy. She's an associate professor of medicine and chief of infectious disease at Upstate. I'm Amber Smith for Upstate's "HealthLink on Air."

Christopher Gaiteri, PhD: What are researchers learning about brain connectivity? Next on Upstate's "HealthLink on Air."

Host Amber Smith: From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Neuroscientists have identified molecules, synapses and anatomy in the brain that give rise to cognitive function, but it's been a challenge to figure out how they all work together. Now, a team of neuroscientists, including a computational neuroscientist from Upstate, have assembled an unprecedented set of data showing that the brain's connectivity is influenced by specific proteins and molecular structures.

Dr. Christopher Gaiteri is here to explain. He's an associate professor of psychiatry and behavioral sciences at Upstate, and he's also an assistant professor in Rush University's Alzheimer's Disease Center.

Welcome back to "HealthLink on Air," Dr. Gaiteri.

Christopher Gaiteri, PhD: Hey Amber, it's a pleasure to be here. I'm really excited to talk about this study.

Host Amber Smith: Well, your work was featured in the journal Nature Neuroscience, and I understand it could lay the groundwork for major advances in the treatment or prevention of brain disorders, including Alzheimer's, dementia and mood disorders. Can you first talk about the 98 people who agreed to be part of the study?

Christopher Gaiteri, PhD: Yes. Most of those individuals were from the Chicago area, and half of them were somewhat unusual in that they're from the Religious Orders Study, so that's a study of monks, priests, nuns, brothers and sisters, and all of them have chosen to provide annual health information to us. They come in, and they'll take cognitive tests. And upon death, all of them donate their brains to science. The other half of the individuals were also from the Chicago area, but they were older adults who were not in a religious order.

Host Amber Smith: So men and women?

Christopher Gaiteri, PhD: Yes. About two thirds were female, but both sexes were there.

Host Amber Smith: So was it hard to find people willing to participate in a study like this, where they would commit to giving their brain to science after they died?

Christopher Gaiteri, PhD: It is hard, and we have people whose full-time job it is to find individuals who are willing to do this. It's a tremendous gift that these people are doing for society. And you might think that when we have -- you know, this subset of individuals in this study comes from a subset of thousands of individuals who've donated their brains -- and you might think that that sounds like a lot, maybe that's enough. But actually, when you're older, most brains have a mixture of several different pathologies in them. And so if you're looking for this exact combination of pathologies, by the time you really drill down to that, you might have two or three people. So that's really not enough to study.

So we're always looking for more. And even Alzheimer's disease, there's sort of several different mechanisms that can be at work in your brain. So it's not really like there's just one form of the disease. So for all of those reasons, it's really important to obtain more brains from people who are willing to do this.

Host Amber Smith: So the 98 people who were part of the study, were they all used in the study, or did you have to whittle down within that 98?

Christopher Gaiteri, PhD: We whittled down to the 98 people. So those 98 people were very unique because they had provided neuroimaging while they were alive and performing all of these cognitive tests.

And then after death we obtained their brains and a whole bunch of different measurements in their brain, so we have the same brain information from it while alive, and then a whole bunch of molecular levels after death. And so that paired data in these 98 people, that's what makes them really special.

Host Amber Smith: Well, I'd like to ask you about the various types of data that were collected by your colleagues at Rush University, University of Alabama, and Emory University. What is functional MRI neuroimaging, and what can it tell you?

Christopher Gaiteri, PhD: So you get fMRI signals out of the brain, based on the amount of oxygen that's being used in a particular part of the brain. Basically, the scanner picks up a different signal when the blood, when hemoglobin is oxygenated versus deoxygenated. And, and you might imagine if part of your brain is working harder, it's going to be using more oxygen. And so that's, that's what fMRI is essentially picking up.

As you're performing some tasks, some mental task in a scanner, we can be tracking "OK, this part of the brain is using more oxygen, versus doing some other task." But actually the people in this study were not doing any task. They were just in the scanner. They could think about whatever they wanted to think about. They had to remain awake. We made sure they remained awake. But the reason that that's useful is because if you're giving someone a task to do, especially this sort of older population, there's going to be some people for whom this task is trivial. There's going to be some people for whom it's actually too hard.

So you kind of have these floor and ceiling effects. And so what we do is we just gather what's called resting state data. And it turns out that if you just observe the brain at rest, with someone lying in the scanner, thinking about whatever they want to think about, that actually provides really useful data that relates to a whole variety of different diseases.

And the nice thing is, it doesn't have these sort of floor and ceiling effects that you might get if you were actually asking someone to do something specific while in the scanner. So that's sort of where the fMRI signal comes from. And again, it's just someone at rest in the scanner thinking about whatever they want to think about. That's what we're measuring.

Host Amber Smith: And then you end up matching that up somehow with the brain biopsy, which can only be done postmortem?

Christopher Gaiteri, PhD: Mm-hmm . Absolutely. And so that's a process of essentially following these people biannually with scans. So some of these people have come in several different times to be scanned, providing cognitive tests.

Once they pass away, we then quickly obtain tissue samples from their brain. Usually it's less than 12 hours after death, we have the brains. And your brain is actually, it's quite beautiful after death. The body really takes care of your brain and buffers it more than anything else in your body. It's your body trying to take care of your brain.

So there's an opportunity to get really accurate data from it even after death. And so again, to your initial question, though, these are the same people who did the scans and then also provided all of these molecular measurements after death.

Host Amber Smith: Now, there was a term in your paper I haven't heard before. What is a dendritic spine? And I'm not, maybe I'm not even saying that correctly.

Christopher Gaiteri, PhD: No, you nailed it. That's what it is. It's a dendritic spine. So, two words, dendritic and spine. Let's talk about the dendrite first. So when you information flows in your brain, it's gathered from the dendrites. These are these little extensions off of neurons. And, they'll gather information from other cells and kind of feed it up into the cell body where it's integrated and then sent out to other cells, where it's picked up by their dendrites. This is essentially how information flows among the cells of the brain.

And so on the dendrite, there's actually these little extensions. If you sort of zoom in, you can see them. There's thousands of these on any given dendrite. And these are the spines. These are the spines of the dendrites, or dendritic spines. And they come in all different shapes. It sort of looks like a forest of mushrooms. There's thin ones. There's ones that are actually called mushroom shaped. And these are the points of contact between two cells. And so that's like a very important part in the brain because the brain's all about communication. And so we're studying the exact point where two cells meet when we study these dendritic spines.

Actually you can ... these dendritic spines, they move. It's really cool. Over the course of hours to days, they can sort of get bigger or smaller or shrink up or form stronger or weaker contacts between different cells. And that's really how you actually substantiate your memory of the world is by these little tiny extensions between cells, the dendritic spines.

Host Amber Smith: So are the dendritic spines involved in the brain protein data that you were collecting?

Christopher Gaiteri, PhD: Yes. In particular, we found that a combination of protein levels and measuring the shapes of these spines was able to predict how statistically connected two different brain regions were. So that's, it's kind of cool because they're very different types of data.

So the dendritic spine data, our colleague Jeremy Herskowitz at Alabama uses microscopes and then actually maps out the three-dimensional structure of individual spines across tens of thousands of these things. So we have that data.

And then you have the abundance of protein, which is just a level more, sort of, more or less. And those two things together, we're able to predict how synchronized two different areas of the brain involved in Alzheimer's disease were. So really, if you think about it, that's three very different types of data that are actually shown to be in sync. You've got the correlations between two distant parts of the brain. You've got the dendritic spines, which is a structure, a cellular structure, and then you've got the protein levels that are coming from inside of a cell. All of those are sort of shown to be in sync by this study.

Host Amber Smith: This is Upstate's "HealthLink on Air" with your host, amber Smith. I'm talking with computational biologist Dr. Christopher Gaiteri about some innovative research into brain connectivity.

Can you describe what connectivity is and why it's important?

Christopher Gaiteri, PhD: Yes. There's a couple different types of connectivity that mean different things in terms of the brain. So the most straightforward one is structural connectivity, which is the kind of thing that we're actually measuring with dendridic spines. We're measuring essentially what is the physical strength of how two things are coupled together.

On the scale of the whole brain, sort of zooming out to the level of the whole brain, you can measure how many fibers, how many sort of cellular structures are connecting to different brain regions. So that's very much a concrete kind of measure of structural connectivity.

Christopher Gaiteri, PhD: FMRI, you can also measure statistical connectivity, which is basically just two brain regions over time, their activities going up and down. Is it going up and down in sync? That's functional connectivity. And so you don't necessarily know why they're in sync. There could be some other third brain region that maybe is synchronizing them together, but you can see that there's a statistical correlation.

So that's the other main type of connectivity that neuroscientists will talk about, is functional connectivity, which is more of a statistical construct versus structural connectivity. There are relationships between the two of them, but those are sort of the two main types that we talk about.

Host Amber Smith: Does functional or structural connectivity change as we age, like naturally? Do you expect to see changes in that?

Christopher Gaiteri, PhD: There's a ton of changes in connectivity as you develop. So if we're talking about before birth, right after birth, there's massive changes in connectivity.

Actually, you tend to lose a lot of synapses early on. It's not so much a matter of like gaining them as sort of pruning out ones that the brain doesn't need. But all through adolescence, there's massive changes in connectivity. A lot of them are related to global integration. Instead of different parts of your brain sort of being isolated, you're kind of developing this global brain network. And that continues up into the 20s. And then it sort of stabilizes until later in life.

Exactly how late depends on the person. But then you start to also see some neurodegenerative changes, which are generally not beneficial, whereas the connectivity changes in development as you're growing up are beneficial. So, there's definitely changes in connectivity. It's not necessarily, it depends on the individual.

The late-life changes in your brain connectivity are generally not as big as the ones that you see growing up. But there are some really severe cases though, where it might almost be on par with that.

Host Amber Smith: So does connectivity help you measure a person's cognition?

Christopher Gaiteri, PhD: We think that, actually, cognition in a lot of cases is essentially generated by connectivity, either the structural connectivity or some of these statistical connectivities that I talked about before. So that's, that's really our perspective is that essentially cognition is given rise to by the way that your brain and your cells are connected. So, yeah, I think there's a very close connection between those two things.

Host Amber Smith: What's important to know about synchrony?

Christopher Gaiteri, PhD: Synchrony between two brain regions relates to how much information you can actually transfer between them. And synchrony's also important for building up connections. So a lot of times in the brain if you see processes that are synchronous, they tend to become stronger and stronger, more strongly connected to each other. So those are sort of two main things to keep in mind about synchrony.

Host Amber Smith: Now let's talk about proteins. How many proteins influence the brain's connectivity?

Christopher Gaiteri, PhD: So in this study we found about 300 different proteins were related to the strength of functional connectivity between two brain regions. And, you might say, OK, is that a lot more than we thought? Is that less than we thought? How does that change?

And the thing is, until this study, there hasn't actually been a really definitive human study of how many proteins are involved in the connectivity of the brain. There's definitely been excellent attempts to measure this, but what we're doing here is we're actually saying in real living humans as opposed to, for instance, dead mice, this is how many proteins that we can actually observe being related to changes in functional connectivity.

And that's really important because in a lot of clinical studies from whatever disease you'll see that, OK, in our patient cohort, people with ADHD or whatever the particular condition of interest is, we notice that there's altered connectivity between these two brain regions.

That's great. That's useful. But, if we're trying to develop drugs for whatever this condition is, it's very difficult to connect those changes in connectivity to molecular levels. And molecular levels are what you're going to develop the drug for, right? So in this study that we did, that's part of why it's, I think, quite important is because we don't only show variation in functional connectivity, but we're actually relating that variation to molecular levels, which is a much more actionable thing than this sort of, just the beautiful connectivity of the brain is one thing, but we're trying to tie it to something that's more actionable, which is molecular levels. So I think that broadly across diseases, that ability is, going to be useful.

Host Amber Smith: Which molecular structures are involved with the proteins?

Christopher Gaiteri, PhD: In particular, we found that the dendritic spines were very helpful in improving our ability to predict changes in functional connectivity, in addition to the protein levels. So essentially, you could count up how many of each particular class of dendritic spine shape was in a particular brain, and that would actually help you to predict how connected different brain regions were with each other. So that's the thing, the dendritic spines, that improved our predictions.

Host Amber Smith: Upstate's "Health Link on Air" has to take a short break. Please stay tuned for more about Dr. Christopher Gaiteri's research.

Thanks for listening to Upstate's "HealthLink on Air." Now, back to our conversation about Dr. Christopher Gaiteri's research.

So how could the results of this study be used to help with Alzheimer's or dementia or mood disorders?

Christopher Gaiteri, PhD: Well, the two brain regions where we gathered the protein data in this study were picked because they're related to resilience to Alzheimer's disease. Resilience is this idea that really comes from examining brains where we found that there are older people whose brains are loaded with Alzheimer's proteins, but cognitively they were fine until death. So in a way, that's kind of what you want to be, right? If you have to have some Alzheimer's proteins, you don't want to be affected by it. Like, you want to be resilient.

And so in studying the brain that we found that the structure of these two brain regions we studied in this study were involved in resilience to Alzheimer's disease. So this study's kind of intrinsically couched in terms of Alzheimer's disease. So we're doing more work currently to tie it specifically to Alzheimer's disease. And in particular, what we're trying to do is, it's fairly easy to obtain a brain scan. It's non-invasive, right? But for studying Alzheimer's disease, developing drugs, you would like to know what are the actual molecular levels in this person's brain? Because given those molecular levels, I might think that this clinical trial makes more sense for this person, and this other clinical trial makes more sense for another person.

So I think we can actually do that, and that's one thing that we're working on now with this dataset is, given the brain scan, what are the molecular levels in this person's brain? We can predict that fairly accurately. And that's the sort of thing that could be used for sending people to one clinical trial or another.

Host Amber Smith: Now, how typical of the general population do you think the religious people in your study are likely to be? Should we consider it a representative sample?

Christopher Gaiteri, PhD: That's an excellent question. There's similarities and differences.So for instance, having a purpose in life is associated with living longer, being healthier in various regards, having slower cognitive design (functioning), and individuals in these religious orders tend to score higher in terms of their purpose in life. So, in that sense, they are not entirely representative of the population. They tend to be more educated, and education is another thing that's been shown to be associated with more resilience to the effect of Alzheimer's disease. You get it later than people who have fewer years of education.

So yeah, there are definitely differences between these people. For the purposes of this study, we tried to statistically control for all of those. And the other half of the individuals, were just sort of drawn from the general population, albeit the population that was willing to donate their brains to science. So again, there may be some special things about them too.

Host Amber Smith: Well, can you tell us about the data set, because I understand you're making it available to other scientists to use.

Christopher Gaiteri, PhD: Yes, yes. It's a huge data set. It is freely available. And many other aspects of it, too, are freely available to any researcher. And these individuals who've all donated their brains to science, their data is used in several hundred papers, actually. So they're having a huge impact.

Host Amber Smith: Is it a spreadsheet, or are there biological samples that you share? How does it exist?

Christopher Gaiteri, PhD: It's so big it's going to break Excel. It's not a spreadsheet, but it's definitely addressable with any sort of programming language. And there are also biological samples. So most of the brains are still available. We don't use up all of them. So if you want to run a study, and you're interested in a particular brain region, and you need it on hundreds of people, that's totally available. So it's a huge resource.

Host Amber Smith: So you think this is already inspiring scientists. Would it inspire them to collect similar data from other areas of the country, maybe, or from other populations?

Christopher Gaiteri, PhD: That would be great. And we do have, there are additional studies,in particular trying to get data from African American and Hispanic populations as well, because those are sort of underrepresented in the data that we have currently.

And I do hope it inspires other people to collect such data. If you're trying to get the exact data we're talking about here today, though, which is the, the fMRI plus the brainomics, that really unusual combination of data, that would probably take another decade to acquire. If you wanted it faster, we're talking about a hundred million dollars. So I would definitely make use of the brains that are already available for this.

There is one similar project -- you're talking about inspiration -- there's a similar or a related project, at least, called the Living Brain Project. In that one, people with typically really severe Parkinson's disease who are getting brain surgery allow scientists to take a small sample of their brains sort of en route to where they're going anyway, surgically. So in that case you do have brain data coupled to people who are actually still alive.

So that's, I guess, another sort of similar study. And that's the only study in the whole world that I'm aware of, that has any sort of similar data. Although in that case, they're mainly Parkinson's disease because almost no healthy person would ever volunteer for this. So it's sort of difficult to have the comparison data. Whereas in the dataset that we've gathered, there's both healthy and diseased individuals. So you, you can make those comparisons.

Host Amber Smith: It really is a unique set of data.

Christopher Gaiteri, PhD: Yeah, I was so excited. I remember the moment I heard about this data several years ago. I thought, this is awesome. I need to do something with this. So, yeah, it's really unique.

Host Amber Smith: You're listening to Upstate's "Health Link on Air" with your host Amber Smith. I'm talking with computational biologist, Dr. Christopher Gaiteri about some innovative research into brain connectivity.

So what sorts of research do you anticipate other scientists may want to do using this data set?

Christopher Gaiteri, PhD: Well, one thing that we're doing, so I anticipate other people would want to do it, is looking at how brain dynamics relate to molecular levels. And you might think that, how is that different from what we did before? Actually as we're talking now, there's a certain set of brain regions that will be active in each of our brains.

And then when you go to your next task and you do something different, you go get coffee, there's going to be a different set of brain regions that'll be co-activated. And actually, even as we're talking, second to second, there's different sets of brain regions that become active, more or less active. And it's been shown that your brain's ability to shift between those different types of networks is actually really related to cognitive functions. So when I say brain dynamics, that's what I'm talking about, the ability to shift between these different networks of co-activated brain regions. So we're sort of taking that perspective on this data as well.

I want to see ... There's something about, for instance, how rapidly someone can flip between different brain networks that relates to their protein level. So if I had to guess what someone's going to do next, that's what we're doing next. So that would be my guess.

Host Amber Smith: Some of the other Alzheimer's research I've read about, they talk about tau and tangles, and I don't hear you talking about any of that. Is that not thought to have a role in Alzheimer's, or does it play a different role that relates to this in some way?

Christopher Gaiteri, PhD: So about a third of the individuals in this study have Alzheimer's disease, and that's clinically confirmed Alzheimer's disease. So the pathologists have gone into their brains, examined slices, and they see those proteins, tau and amyloid proteins that you're talking about. So they definitely have it.

Another third of the people have those proteins, but actually were cognitively fine. So those are the resilient people. So we're talking about two thirds of the people in this study having those proteins. So those proteins are definitely evident in the brains that we're studying.

There wasn't exactly room to incorporate that into this study as well, but that's something that we're also working on currently, is incorporating those proteins.

Host Amber Smith: I was going to ask if there's additional research you and your team may do with this data set, but that's maybe one thing?

Christopher Gaiteri, PhD: Yes, that is one thing. And another thing that we're doing that's maybe slightly less mainstream, but becoming more mainstream, is we want to tie these effects that we're seeing to a particular type of cell, like a really specific type of cell. Not just a neuron or oligodendrocyte or a microglia -- those are broad classes of cells -- but like really drill down within those. What type of cell might be responsible for this?

And the reason for caring about that is because if you can do that, then you can essentially focus in on that cell. You can grow it in a dish and do experiments on it. And it's much more, more rapid. And so we can essentially count up how many cells of each type are in the brain of each of these people because their brains are still around. We still have access to their brains. We can do this. It's just sort of held up by the fact that it's fairly expensive. It's about $4,000 per sample to do this.

And you want to do it in a couple hundred people in a couple brain regions. So you're well into the millions of dollars at that point. But, these people who've shared their brains and been neuro imaged are so rare. I think they could really be a Rosetta Stone that's going to be useful for a variety of diseases. So I think it's really important to continue investing and, and measuring data in these exact set of brains.

Host Amber Smith: Is there a theory that Alzheimer's starts with one cell?

Christopher Gaiteri, PhD: That is a very interesting hypothesis. You could name it after yourself if you want to. It's always up for grabs. There is a question about, like, what is the first cell that's going to sort of flip into an Alzheimer's state, and is that cell going to then influence other cells that it's connected to and induce those to flip into an Alzheimer's state? Or is it, for some individuals, more of a issue of genetic destiny, and there's these internal molecular aging clocks, and at some point the clock rolls over to a certain number, and it flips a switch and a whole bunch of cells begin to have issues?

Or is it that in perhaps a buildup of different exposures, environmental exposures begins to initiate this in a broad variety of cells? Or maybe there's something about the activity of a particular cell type. It just gets utilized by a way, sort of a high wear item in the brain, and it essentially becomes the first target of Alzheimer's disease.

So, if you want to join me in Alzheimer's research, we can try to figure this out. It's possible that it starts somewhere, and we're very interested in those earliest transitions towards Alzheimer's disease. So I like the way you think about this, but I think that's kind of an open question.

Host Amber Smith: Well, it's clearly very fascinating research, and I really appreciate you making time for this interview, Dr. Gaiteri.

Christopher Gaiteri, PhD: Oh, it's been such a pleasure to speak with you. Thank you.

Host Amber Smith: My guest has been Dr. Christopher Gaiteri, a computational biologist and associate professor of psychiatry and behavioral sciences at Upstate. I'm Amber Smith for Upstate's "Health Link on Air."

Here's some expert advice from exercise physiologist Carol Sames from Upstate Medical University. What exercises do you recommend for seniors?

Carol Sames, PhD: So generally, I usually, when I talk to seniors, I say, what do you enjoy doing? Because this is a lifestyle change. So you don't want to have people engaged in an activity they're not interested in. Not surprisingly, most seniors engage in walking. It doesn't require any types of equipment. It's fairly straightforward. Of course, you need to have a place to walk. But here in Central New York, we do have a lot of wonderful places that we can go. Winter's a little bit more challenging, but a couple of the malls will have indoor facilities that you can walk in early in the morning before they get busy.

But if somebody says something like, I really enjoy yoga, or I really enjoy my water aerobics class, wonderful. If somebody says I have a stationary bike that I've been using to hang my clothes on, but I'm going to use it now, wonderful. The whole idea is that I want to be consistent, that I want to try to achieve the activity guidelines. And so whatever that activity is, great. If you want to mix it up, wonderful.

Host Amber Smith: You've been listening to exercise physiologist Carol Sames from Upstate Medical University.

And now, Deirdre Neilen, editor of Upstate Medical University's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: Lane Falcon's poems can be found in American Poetry Journal, New York Quarterly, and Rust & Moth. Her poem "Escape from Cincinnati" describes a mother's awareness of the paradox contained in fentanyl, a drug that can ease her son's pain as he is suffering in the hospital, yet a drug that is killing and addicting the city's inhabitants.

"Escape from Cincinnati"

I still haven't gone back to that place -- the vacuousness

I felt while they dripped fentanyl into my son's bloodstream

after his second reconstruction surgery. How I'd go

on a panicked run every day in a city where opioids reigned

where a man fell to his knees, a woman froze under the overpass.

In the waiting room, a grandmother cried, her daughter

just dead from overdose, her grandson just waking

from general anesthesia. How messed up it felt

that night when I begged the nurse to hurry

and give my son more drugs, enough to sustain him, dull his pain

and mine, his pupils blooming with fear when he started to wake.

How small a measure they lent. How small the graces we get

when we're rowing in grief.

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York.

If you missed any of today's show or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org.

Upstate's "HealthLink on Air" is produced by Jim Howe, with sound engineering by Bill Broeckel and graphic design by Dan Cameron.

This is your host, Amber Smith, thanking you for listening.