The Long-Lasting Effects of Delirium: Tammy Hshieh, Ed Marcantonio, & Thiago Avelino-Silva

Eric 01:14

Welcome to the GeriPal Podcast. This is Eric Widera.

Alex 01:19

This is Alex Smith.

Eric 01:21

And Alex, today we’re going to be talking about the long-lasting effects of delirium, including its effect on dementia and cognitive impairment. Who do we have to talk about this topic with?

Alex 01:30

We are delighted to welcome Tammy Hshieh, who is a geriatrician at Beth Israel Deaconess Center in Boston, and she is first author of a JAMA Internal Medicine paper titled Rehospitalization and the Association of Postoperative Delirium with Cognitive Decline in Older Adults. Tammy, welcome to the GeriPal Podcast.

Tammy 01:53

Thank you. Happy to be here.

Alex 01:55

And we are delighted to welcome Ed Marcantonio, who is a geriatrician and section chief for research in the Division of General Medicine at Beth Israel Deaconess Medical Center in Boston and co-author on the study that we just mentioned that Tammy was first author on, also authored a 2017 paper in NEJM called Delirium in Hospitalized Older Adults and a 2025 commentary in JAMA Internal Medicine, Improving Delirium in Hospitalized Older Adults. And Ed was the fellowship director when I did my research fellowship at Beth Israel Deaconess Medical Center some time ago. Ed, welcome to the GeriPal Podcast.

Ed 02:34

Thank you so much, Alex and Eric, for inviting me. And perhaps I had some small role in starting GeriPal.

Alex 02:42

Absolutely. Yes. Ed was a major influence on me early in my research trajectory. Thank you, Ed. We’re also delighted to welcome back Thiago Avelino-Silva, who is a geriatrician and now newly minted faculty in the UCSF Division of Geriatrics and author of a commentary on Tammy’s paper. That commentary is titled Cognition After Postoperative Delirium: The Confusion Has Cleared, But All Is Not Well. Thiago, welcome back to GeriPal.

Thiago 03:14

Hey everyone. Thanks for having me too.

Eric 03:17

And we will have links to all of these articles in our show notes for this podcast. And before we get into this topic, who has a song request for Alex?

Thiago 03:27

I do.

Eric 03:28

What is the song?

Thiago 03:30

How about Where’s My Mind by the Fixies?

Eric 03:33

Why did you pick this song?

Thiago 03:36

Well, I think because that’s something that, you know, often patients have told me after they experience delirium, like, how scared they were and felt like they were losing their minds.

Eric 03:51

Perfect. Well, next week, let’s go.

Alex 03:54

We actually did this one in 2019, but if it’s been a while, sometimes I’ll play a song again. I know Eric loves this one because I think it’s one of his favorite movies, Fight Club. Here we go.

Alex 04:12

(singing)

Eric 04:50

Fight Club, such a good movie.

Alex 04:52

Such a good movie. Such a good final scene.

Thiago 04:56

Great sound track.

Alex 04:56

Everything’s collapsing. Yep. Yeah. Thank you, Thiago. Good choice.

Eric 05:01

So let’s talk about Where Is My Mind? Let’s talk about delirium. I’m going to start off with — I’m going to go back, what, a decade ago, nearly a decade ago, to Ed. You wrote a New England Journal review on delirium in hospitalized older adults, and you said delirium can be thought of as like an acute brain failure, a term that I loved, and as the final common pathway of multiple mechanisms similar to acute heart failure. Do you still think that way?

Ed 05:34

Yes. I still think that the acute brain failure analogy is good. I actually, in some ways, prefer now using kidney function instead of heart as another organ to think about.

Eric 05:50

Why is that?

Ed 05:51

So, you know, people with chronic kidney disease, which you could analogize to dementia, are at increased risk. for acute renal failure. And similarly, people with dementia are at increased risk for delirium. But also, people with no prior chronic kidney disease can get acute kidney failure. And that’s true in delirium too. People with healthy brains can get it.

And the acute renal failure can vary greatly in severity to a mild creatinine bump all the way up to dialysis. And we see that in delirium too, and it recovers variably. Some people recover completely, and some people have long-lasting effects after an episode of acute kidney injury. So, I think there’s a lot of similarities between the two.

Eric 06:51

Let me ask about that, Thiago. When we think about delirium, do you think about it as like a transient You know, acute to subacute phenomenon, change in mental status, inattention, or what are the longer-lasting effects if there are longer-lasting effects?

Thiago 07:08

Yeah, I think the confusion, pun not intended, but I think the confusion is that I think both things happen. There are many elements or even cases when you can have a transient kind of episode with, you know, very little long-term consequences, but there are a number of patients that clearly have a different kind of trajectory and that, you know, have — do have long-term consequences and often don’t recover or don’t go back to their, you know, previous baseline.

Eric 07:43

Well, I’m going to play more out this, is it akin to acute renal failure or acute heart failure? In both of those, there are clear mechanisms that we have in our head of why somebody’s in acute renal failure. We can drill down to the pathophysiology of what’s going on. Is it the same for delirium?

Are we at a point with our medical knowledge we know exactly why somebody is becoming delirious, and if we can just avert that or treat that, they may recover? Still may not, but they hopefully may. I guess it’s like ATN, like, I know what’s causing this.

Thiago 08:23

Yeah. Another challenge is that delirium is multifactorial, and there are a number of different things usually going on. And also that relates to the mechanisms. You often have more than one mechanism underlying the delirium. But I think that Ed would be a great person to pitch in on the mechanisms and what he thinks might lead to these long-term consequences.

Ed 08:47

Sure. Well, just to say, you know, and maybe nephrologists will disagree with me, but in my opinion, the brain is a more complicated organ than the kidney. And it’s, you know, kind of protected in the CNS. So I think it’s a little harder to figure out what’s going on in the brain than in the kidney. But I would say in the past 10 years, we’ve learned a lot. We still need to learn a lot more, particularly about this link between the acute delirium and the long-term consequences.

I like to think of 2 main mechanisms. One is neurotransmitter dysfunction, which may be related to medications or other factors. But the other factor that may link with the long-term consequences is inflammation and neuroinflammation. And that’s increasingly recognized as an important mechanism in dementia too. There have actually been mouse models where they’ve done a surgical insult or other insult, and you see, you know, this big inflammatory blast in the mouse blood, but then they dissect the brain and that inflammation goes into the brain too.

So the brain becomes inflamed when the body becomes inflamed. And actually older, frailer people are at more risk of having the inflammation go into the brain than younger people, although it can happen to anyone. So I think we need to do more. We’ve not gotten to the point of therapeutics yet, although we may be close, but I think we, do have an important lead in that area.

Eric 10:38

Well, what’s the, what’s the close? What’s the lead? Do you have an inside scoop?

Ed 10:42

You’ll have to have me back another time, I think, to talk about that.

Alex 10:49

Can’t reveal it. We did, we did have a teaser on a recent podcast about hot new drugs, and one of them we covered were DORA, which are, what are they? Dual Orexin receptor antagonist, which is a medicine that may improve sleep architecture rather than, you know, all of the other sleep meds, which seem to make things worse rather than better. You’d think, oh, if I can help them sleep more, I’d make it better. But usually when you do that, you end up messing with sleep architecture and make the delirium worse in older adults. Tammy, any thoughts on anything we’ve said so far?

Tammy 11:26

Yeah. Well, I think clinically I still tell my patients exactly what had described like 10 years ago that this delirium phenomenon is brain failure. But this new generation of patients are a little bit different from my experience that they’re even more proactive about their health than the previous generations. And so, when I say that, you know, this is an acute brain failure, you know, we hope that you’ll snap out of it or we’ll help you get out of it, they have lots of questions that come afterwards of, What does this mean?

What are the long-term impacts for me? What can we do as a family to get our loved ones better? So I think the field is changing both on the side of the research and what we are doing in our examination of delirium. But I think on the patient side and the families, they have a lot of questions and a lot of proactive desire to like understand the multifactorial aspects of delirium better on their —

Alex 12:22

Mm-hmm.

Tammy 12:23

Well, this is kind of exciting.

Alex 12:24

I love that.

Thiago 12:25

Yeah, that, that’s something that interests me a lot because it’s actually difficult to answer these questions oftentimes, right? Because there’s so much heterogeneity and variability on what, you know, can happen. And we only know these kind of averages of, you know, prognosis. So I definitely think that’s something that we should look more into.

Alex 12:47

But before, I know we want to get into the meat of Tammy’s study. Before, can I just ask about a couple of debates, controversies within the field? And sometimes controversies and debates within the field are really healthy and they move things forward, and sometimes they’re like roadblocks. They’re like, you know, internecine battles that just playing out for no particular — one that I view from afar, because this is not my primary area, is this conflict between neurologists who call this encephalopathy and geriatricians who call it delirium.

Is that a real issue that may limit progress in this field or not? And that’s number one. And then the number 2 is, you know, which screening tests should we use? And a lot of Europeans use one test and we tend to use the CAM more or a NuDesk, and they use, what is it, the 4AT, I think. Does that like, uh, do those battles matter? Are they healthy for the field? Are they unhealthy? I don’t know, Ed, maybe you could start with those issues.

Ed 13:47

Well, I’ll say, in terms of your first question on delirium versus encephalopathy, there was a consensus statement that came out in 2022 that had 10 different fields. I’m not sure if neurology was one of them, but it did clarify that delirium should be used for the clinical syndrome and encephalopathy used for actually the mechanism going on in the brain. And there are about 40 other synonyms for delirium out there too that are used, like acute confusional state, altered mental status, and so forth, and those should not be used.

So at least we’re down to delirium and encephalopathy with a slightly nuanced difference between the use of those 2 terms. In terms of the screening tools, you know, I’d say, you know, I have some vested interest in this because I’ve developed a couple of the screening tools myself, the 3D-CAM and the UV-CAM. And of course, I think that the ones that we’ve developed are the best. And, you know, they’re based on the CAM algorithm, which I think is a reproducible phenotype, which is really important. And if you’re doing like a CAM ICU, it’s useful to then use a CAM-based tool won awards. So, you know, part of me says, yes, there are definitely better ones than others.

But then I’ve also heard this analogy of cereal, which is that, you know, there you go to the supermarket and there are lots of different types of cereal out there, and someone comes out with a new cereal and people are not that upset about it because The more cereals there’s there, the more cereal that’s bought, and that’s better for the overall field of cereal. So you could think of the same thing for delirium screens.

You know, doing some screen is clearly better than doing no screen, and different people are going to have different preferences. So the more options, the more cereal boxes of delirium screens out there, the better.

Eric 16:02

Yeah, I mean, Thiago, do you agree?

Thiago 16:04

No, I agree. I was going to say that one thing is that I do think that everyone needs a delivery room screen. Not necessarily everyone needs serial. So I think it’s, you know, for us it’s even more important. Uh, but, but I agree that, you know, the one advantage of having all these different options is that you do have a lot of differences in, you know, the, you know, different settings have different needs and kind of patient characteristics.

You know, you might have places like in Brazil where literacy might be a limitation for some of the tests. So having, you know, different strategies to screen and test for delirium, I think, is important. But, you know, you should be definitely doing something about it wherever you work.

Eric 16:57

I heard one point of caution, and I would love your thoughts about this, is just doing delirium screens in the hospital for all older adults probably is actually a bad policy if you don’t do anything about it. Tammy, what do you think about that?

Tammy 17:14

Oh, I definitely think that having a controversy is better than not. You know, even then, delirium is still kind of underdiagnosed. In the field. But definitely we do need to move in some ways beyond just all the different options for screening, which are great as like educational tools to think about the field. And, you know, what are we looking at now?

Are we looking more at dementia patients or delirium severity? Right. But you’re right. Once you find delirium, what do you do about it? That’s the most important part. And that’s what’s the most exciting to me too, is What do we do with all of these screening tools and what do we do when we find delirium on floors?

Alex 17:58

Does anyone know, you know, the new CMS Age-Friendly Health Initiative measures, which hospitals are incentivized to comply with, do they only require tracking delirium assessing or do they also require that you develop an action plan based on that assessment? Does anybody know? Not a fan.

Thiago 18:17

From what I recall, they only require that you measure it. They don’t require, you know, interventions related to it. Yeah.

Eric 18:26

Maybe we’ll have a link to our show on CMS age-friendly measures in the hospital setting, and you can actually pull up — I don’t remember it either. Maybe we can move on to Tammy’s article published in JAMA IM. Tammy, before we talk about your article, what did we know about the relationship between delirium and long-term cognitive function before your study?

Tammy 18:51

So we knew that delirium was associated with a lot of poor clinical outcomes, and we did know that there was a correlation between delirium and long-term cognitive impairment. We also know it’s kind of a vicious cycle of people who have dementia and other types of cognitive impairment are at higher risk for delirium in the hospital or in other settings. But I think what we added to the literature with the study was looking more specifically at whether or why delirium is associated with long-term cognitive impairment.

So in other words, is delirium a marker for frailty and comorbid illness, and that’s why it’s connected with long-term cognitive decline, or is it doing something to people’s brains and their cognition and causing the long-term cognitive impairment instead in its own right? So in 2023, we had our colleague Zach Kunicki had published a paper looking at the association between the two. What we wanted to do this time was to extend on that to see if it was a marker, delirium as a marker. Or was delirium more intertwined with long-term cognitive impairment?

Eric 20:05

And briefly, how did you actually try to tease that apart?

Tammy 20:09

So what we looked at was we looked at the correlation between delirium and long-term cognitive decline in our cohort of patients over a trajectory of 5 years. And we had developed a GCP, so kind of a global, a general cognitive performance score that we used to reassess patients at a number of time points in those 5 years. And then we looked at the patients and what else had happened to them during those 5 years to get a better sense of their cognition and their cognitive trajectory with and without these other things happening and with and without delirium.

Eric 20:48

And who was included in the cohort of patients?

Tammy 20:51

So, it was the SAGES study. It was a cohort of 560 patients in the greater Boston area. that were older and getting ready for elective surgery.

Eric 21:03

So, and then —

Alex 21:04

postoperative. Yeah. So, post-op delirium. What do we know about how post-op delirium might be different from, say, delirium on the medical wards?

Tammy 21:13

It’s a good question. We know that post-op delirium is because it’s operative, and especially in this cohort, it was elective patients. We had submitted these patients to a certain kind of trauma, right? caused them to have a sentinel event. And we were causing inflammation, we were causing neurotransmitter disruption. And so, in this cohort, you could say that in some ways it’s a little bit more controlled in the things and the variables we could look at. But they also have gone through something that’s a pretty big whack to the system.

Eric 21:49

Is this all types of surgery or just those with general anesthesia or?

Tammy 21:54

Yeah, it was all types of surgery, but major elective surgeries, and most of them were orthopedic surgeries.

Eric 22:00

Okay. And then you followed these people after their surgery. You saw what their cognition did post-surgery, right? And then you followed them up to 5 years.

Tammy 22:11

Up to 5 years, exactly, which is not often done in delirium research and cognitive research. Yeah.

Eric 22:18

And what did you find?

Tammy 22:21

So what we found was that it was interesting and kind of like we expected that patients who had been rehospitalized multiple times during those 5 years, their cognition did have a noticeable and statistically significant decline during that period. And so I should back up and define rehospitalizations as a measure that we were using to hopefully capture frailty and comorbid illness. It included rehospitalizations, rehospitalizations with ICU stays during those rehosp — rehospitalizations with post-acute care stays.

We used that as a marker. And so, we found that kind of like we were suspecting, the patients that had multiple bad things happen to them after the first elective surgery had the cognitive decline. But we also noticed that patients who had delirium during their first elective surgery procedure and hospitalization, they had a more significant cognitive decline in the 5 years afterwards. So with all of that information, then we wanted to know exactly what was going on between the rehosp and the delirium. And in our analysis, we found that the rehospitalizations actually didn’t mediate the trajectory of cognitive decline quite as much as the delirium did. So in

Eric 23:43

other words — What does that mean, didn’t mediate?

Tammy 23:46

Yeah. So delirium still has the strongest impact on long-term cognition than any of the other things that happened in those 5 years to those patients.

Eric 23:57

Well, let me go back to the first question about, I think I asked Thiago about, is delirium transient and are the effects on cognition transient? Did you notice that like everybody worsened, some groups worsened? Did, like, did they get back to baseline from their Cognitive function?

Tammy 24:14

So none of them actually got back to baseline for cognitive function if they had delirium. The patients who had multiple things happen to them afterwards, their cognition decline was even worse than those who didn’t have other things happen to them afterwards. And so it really kind of underscores the idea that delirium isn’t as transient as we used to say or we used to think.

Eric 24:41

Thiago, you wrote the editorial for this paper. Did the findings surprise you?

Thiago 24:46

No, the findings did not surprise me because probably because I would, I was like rooting for the findings because that’s what I think happens in a way. Like, I wasn’t rooting for people to get worse, but I do think that delirium, you know, independently, like in itself, leads to worsening of the cognition. And when we talk about this, there’s still a lot of pushback of people that, you know, believe that delirium is only kind of revealing underlying impairment and that it isn’t itself a driver of decline.

And I think studies like this, you know, which was like a great one, and kudos for Tammy and her co-authors for leading it. Really important to show the independent effects of delirium long-term on cognition. And it’s really cool in that if you think about it, if delirium is something that independently leads to cognitive decline, and we know that we can prevent delirium, then there is, you know, one cause of dementia that we could potentially prevent. Which, you know, a lot of times isn’t true.

Eric 26:06

Ed, what did you think about it? Does this kind of seal the idea that delirium does cause dementia rather than unmask it? Or maybe there’s like some shared mechanism that puts you at risk for both?

Ed 26:20

Yeah. So I’ll just say I’m glad that Thiago wasn’t surprised. I think the investigator team, was surprised by our results. Why is that? And just to restate them again, because it is a bit of a subtle message. So we knew from the previous Konicki paper, 2023, delirium was associated with faster cognitive decline.

Eric 26:46

Yeah.

Ed 26:46

So in this paper, we found delirium was associated with rehospitalization, and we kind of expected that. We found that rehospitalization was associated with cognitive decline, albeit a somewhat more transient cognitive decline. Then we, when we put them all together, we thought that those rehospitalizations would explain a good portion of the delirium-related cognitive decline, but it did not.

It was a trivial percentage of the cognitive decline from delirium explained by the rehospitalizations. Most of it was the independent direct effect of delirium on cognition. The delirium hospitalization cognition was a trivial part of that equation.

Eric 27:35

Yeah. That only potentially is one shared mechanism, which is hospitalization, which I guess you could make an argument that’s associated with frailty, but that’s kind of a stretch. Like there could be a lot of other things That maybe underlying mechanisms — did you account for all those things? Did you, or was it just hospitalizations that you were looking at, Tammy?

Tammy 28:03

So we looked at rehospitalizations, and then we also looked at what happened during those rehospitalizations, like the stays, to reflect not just the rehospitalization, but the severity of the rehospitalization. We also looked at post-acute care stays after rehospitalization. Because the thought was that that would capture functional decline or a functional reason that someone would be rehospitalized and is relatively frail.

So we thought that rehospitalizations were a good measure to use because it kind of captures a multifactorial reason for someone to be at higher risk, I think, for delirium, poor outcomes, frailty, comorbid illness. And we did also look at, you know, the trials and comorbidity and how many people had some kind of cognitive impairment to begin with. But the thing that we wanted to look at was some measure for frailty and comorbid illness to kind of answer this question of, is delirium just a marker for frailty or is it something more than that?

Eric 29:11

And then if we think there’s a causative component here with delirium, I’m going to go back to the mechanism question. What do you think the mechanism is?

Ed 29:21

Well, I’ll start. So we purposefully picked an elective surgery cohort so that we could completely characterize the participants before they had the surgery. So they had detailed cognitive testing, some had neuroimaging, blood tests, and so forth. And then they came in for their surgery, and we studied them for delirium. So, it would be hard to do a similar study in medical patients where obviously the hospitalization is unplanned.

And as noted, I think, in the editorial, many of the patients are delirious by the time they reach the hospital. So, it’s difficult to get a baseline. But certainly, the Surgical insult can cause an inflammatory cascade that can lead to effects on the brain. The patients are also getting a lot of medications perioperatively that can affect the brain. Postoperatively, many continue to get opioids or other medications that can affect the brain. So, I think it’s a combination of, again, delirium tends to be a multifactorial

Eric 30:38

Yeah.

Ed 30:39

Syndrome. So lots of different etiologies. What causes the ongoing is harder to know.

Thiago 30:48

Yeah. There’s been like increasing number of studies on like the vascular components of delirium. Do you think those might, you know, play a role into the long-term effects as well?

Ed 31:01

Yeah. So as part of the SAGES study, which was a program project, In addition to the core epidemiological clinical study, there have been biomarker studies. There are also neuroimaging studies, and there is evidence that people with preexisting cortical atrophy and other brain evidence of brain pathology are at increased risk of both delirium and also the long-term cognitive decline after the delirium.

Eric 31:36

So even in this cohort, there may have been some underlying brain pathology going on that put them at risk for developing delirium. We may not have picked it up on the cognitive testing, but it may have been there. And then it further unmasked this underlying —

Alex 31:51

Back to unmasking.

Eric 31:53

Neuropathology.

Alex 31:54

I thought we were going away from unmasking.

Eric 31:56

I don’t know.

Alex 31:57

I’m just trying to keep it straight.

Thiago 32:00

Yeah, but, but I mean, I think, again, I think that, you know, all these things do happen. It’s not one or the other. Right. It depends on like the severity on the, you know, this interplay of vulnerability and the severity of the insults that you get, right? So you might have some underlying pathology, a lot of it that, you know, just, you know, that, that would make it very vulnerable to inflammation and, you know, to the consequences of inflammation.

And then you could have healthier brains that, you know, could still be affected if you have a lot of inflammation and have, you know, damaging effects from that inflammation in the long term too.

Eric 32:45

Yeah. And the long term, I’m going to go back to the kidney analogy. Is it like you developed acute kidney injury, you’ve knocked off now a couple of those nephrons, So, you never get back to your GFR despite actually looking like you’ve fully recovered. Is that the thought here?

Tammy 33:04

I like that idea because I often think about reserve and resilience for our patients. And so, we don’t really know necessarily what we’re working with at the beginning, how much reserve a patient might have or their brain might have. But kind of like the kidneys, once you have an insult, you tap into that reserve. And the more you tap into it, if you’re unlucky, the more depleted you become and the more, I guess, unmasking of the vulnerability of the brain.

Alex 33:31

Yeah. Yeah. A couple of meta thoughts that have come up along the way. One is in terms of the postoperative opioid use we did have on, again, on that episode on hot new drugs, there’s a sodium channel blocker that was studied in what, bunionectomy and Hernia surgery, some other —

Eric 33:51

Liposuction.

Alex 33:52

Liposuction, right? Probably not a big part of SAGE’s study, but it is good that potentially we’ll have non-opioid medications for pain, and then hopefully we’ll be able to spare older adults some of those medications and try and reduce at least one of those factors in the mix that are deliriogenic. The other is like, boy, if you could go back in time and do this study again with unlimited resources, I’m sure there are all sorts of things you could do.

And vis-à-vis the kidney analogy, You know, in kidney disease you could do like kidney biopsies, right? We don’t typically do brain biopsies, but boy, wouldn’t it be interesting? That’s one of the limitations and the challenges in this area. But did occur to me that you might have wanted to like go back and do more like people when they like eFrailty, right? Like which we, your colleagues have developed, right? We’ve had several of your colleagues on talking about the eFrailty and the compendium of frailty calculators.

Rehospitalization is not one of them to my knowledge, but there are certainly many other measures of frailty out there. I would guess that if you could redo this study from the outset today, you’d probably incorporate one of those measures. Is that right? I see you shaking your head, Tammy.

Tammy 35:05

That’s right. I’m trying to think back because this was a project that took like 4 years, I think, Ed, in the making. And we did so many iterations because SAGES has such an amazing amount of data, but we had to eventually kind of pick and choose which ones we use. So in the beginning, we were hoping to look for all new diagnoses that happened to patients in those 5 years, any new cancer diagnoses, new dementia diagnoses. We were hoping for heart failure exacerbation data.

There was a lot that we were kind of going through to try to incorporate into this because delirium is so multifactorial. Cognitive decline is so multifactorial. So, if we had all the resources and all the statistical, like, willpower available, I think we would have loved to, like, incorporate some of that information about new diagnoses and maybe even, like, psychosocial, socioeconomic, other factors. It would have been really neat to look at all of those things. Yeah.

Ed 36:09

Just to say, we didn’t do the frailty study. Actually. So yeah, we did measure both the FRIED phenotype and the frailty index, and we published it in JAGS about a year ago.

Alex 36:28

Oh, great. I should know that. Yeah. Good.

Ed 36:31

Where we found that frailty was associated with delirium and people who were more frail had a higher risk of delirium, but it was not a huge effect. It was statistically significant, but this is total recall. It was about a doubling or slightly less than doubling of effect in frail versus robust, and the pre-frail groups were kind of in between.

Alex 37:01

And did SAGES measure frailty longitudinally?

Ed 37:04

We did.

Alex 37:05

You did great.

Ed 37:06

We haven’t done much with that yet. Oh, it’s a great dataset. Many papers still forthcoming.

Alex 37:13

Seems like there’s an opportunity there, right?

Eric 37:16

All right. I got a question for Iago. You mentioned delirium is preventable. I’m just hearing all this data. How preventable is it? Is it a never event or do we think like maybe we can prevent a little bit of it?

Thiago 37:31

You know, Sharon’s and Ed’s groups are really leaders in delirium prevention. And I guess overall, the numbers usually suggest that you can, you know, prevent from about a third to 40% of the cases. The one caveat to that is a lot of patients already are already admitted to the hospital with delirium. So maybe half to two-thirds of the patients, medical patients at least, who experience delirium already have it when they arrived at the hospital.

So, these cases, we are kind of obliged to focus more on recovery and management. But of those patients who do have incident delirium, then, you know, we could prevent about a little over a third of them, at least.

Eric 38:19

In addition to like a hospital elder life program, are there other key things since your New England Journal review ad that that we should be doing for delirium prevention? Well,

Ed 38:30

I’ll just say that going back to a very early study that I did, also published in JAGS, we found that proactive geriatric consultation for surgical patients had a similar effect for prevention of delirium.

Eric 38:49

And that also included, if memory is correct, you looked at medications in that

Ed 38:54

Yes, definitely.

Eric 38:55

Prior to, I suppose, the Hospital to Life program.

Ed 38:58

Right. I think there’s a medication component, at least in terms of sleep hygiene, preventing sleeping meds and help.

Eric 39:07

On-farm sleep hygiene and help.

Ed 39:09

Right, right. So yeah, meds are always important in any setting, I would say. I see evidence. It’s very hard to say that the delirium rates are coming down slightly over time in well-done studies. The incidence are somewhat lower now than they were maybe 20 years ago, and some of that, I think, does relate to just better overall care of older adults in the hospital. But that’s not to say we don’t have a lot of room for further improvement.

Eric 39:45

Any other big updates as far as managing delirium once it happens.

Thiago 39:52

I think that it’s not that there are like new things, but I think that we still are not doing the things that we know we should be doing. I think that’s more the focus, right?

Eric 40:04

Promoting sleep, hydration, looking at their meds.

Thiago 40:09

Controlling pain, engaging family and care partners. All these things that, you know, are really Not that, you know, these are all low cost, you know, should be fairly easily done, and we still don’t do them. So we don’t have a magic pill to prevent delirium or to treat it, but there are a number of things that we know that work. So that’s what we should be doing.

Alex 40:35

And despite what I said about exciting hot new drugs, those studies are very early, not ready for primetime use. And I think the main point for me from Tammy’s study is that You know, this elevates the importance of assessing delirium because of the long-term consequences on cognition. And to me, we’re at a really exciting time because we have these CMS, you know, healthy aging initiatives that I think, I hope, are really going to boost hospitals’ attention to this important factor.

And if we measure it, then the next step is we can do something about it. We can study, we can learn, we can improve care further on a national level for people with delirium. So to me, this is really the beginning of an exciting time, and it would be great to see studies that follow people long-term with different treatment strategies for delirium, prevention strategies for delirium, and show an impact on long-term cognition. That’s where we need to head as a field. I see Ed nodding and Tammy nodding their heads. Yes. Thiago nodding their head. Yeah.

Thiago 41:41

Very well put for a non-delirium researcher.

Eric 41:47

Well, maybe before we end, real quick lightning round, since Alex got to say that, like one thing you think should happen if you had a magic wand, what happened next? Could be research, could be clinical work around delirium prevention or treatment. Thiago?

Thiago 42:05

I would like people to start believing the mounting evidence that delirium is an independent cause of cognitive decline. I think that would move a lot of things in the field.

Eric 42:16

Tammy?

Tammy 42:18

I think I would like — I think I sound like a Luddite or something, but I would like people to think about the low-tech but high-touch things that we can do to prevent delirium. I think we’re still kind of focused on running after the next big thing, AI or whatever, but I think there’s so many things we can do already for delirium. That is low-tech but high-touch and can make a huge difference.

Eric 42:41

Wonderful. Ed, finish us off.

Ed 42:44

Yeah, I agree with both Thiago and Tammy and would just say that I think for still too many people, delirium is a behavioral disturbance that basically disrupts the unit and is a nuisance for everyone. And we just need to get rid of it. And I think really changing that mindset to know this is acute brain failure. This is a brain that’s at risk. We got to take this seriously. We got to figure out what’s going on and we have to put a treatment plan in place. And that may be a long-term treatment plan for some people.

Eric 43:23

Wonderfully said. Alex, with your feet on the, in the sky and your head on the ground.

Alex 43:28

Feet in the air and your head on the ground. Feet in the air, head on your ground. Here’s a little bit more.

Alex 43:40

With your feet in the air and your head on the ground,

Alex 43:49

(singing)

Eric 44:19

Tammy, Thiago, Ed, thank you for joining us on this podcast. Thank you.

Tammy 44:23

Thank you. This was fun.

Ed 44:25

Thank you.

Eric 44:26

And thank you to all of our listeners for your continued support.

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