Delirium and Dementia: Plenary Preview with Dr. Sharon Inouye

Sharon Inouye, PhD
Sharon Inouye, PhD

AAIC Special Series Part 4:

Research into delirium, a condition where older adults experience acute confusional states during hospitalizations, and its connections to dementia have led to  numerous advancements in hospital care and treatments. Dr. Sharon Inouye joins the podcast to discuss how our understanding of delirium has changed over the past 30 years and previews her upcoming AAIC plenary talk about the intersection of delirium and dementia.

Guest: Sharon Inouye, PhD, director, Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, professor, Harvard Medical School

Show Notes

AAIC is the world’s largest forum for the dementia research community. Register for the plenary events, which are free to the public with registration, at the AAIC website.

Learn more about Dr. Inouye at her bio on the Marcus Institute for Aging Research website.

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Dr. Sharon Inouye Excerpt: The biggest thing in delirium is that delirium really is a thing, right? It's now a thing. It's an accepted field. It's an important area of investigation. It has DSM-5 and ICD criteria. It has tools to recognize it. So delirium really is a thing and we couldn't say that thirty years ago.

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: We’re back with another episode of our AAIC special series, where we preview some of the plenary talks and get to know the presenters in the lead up to the Alzheimer’s Association International Conference from July 31st to August 4th. Interested in hearing more from the conference and the groundbreaking research being highlighted? Register for free access to the virtual, plenary events on; the link can be found in the episode description. Today I’m joined by Dr. Sharon Inouye, director for the Aging Brain Center at the Hinda and Arthur Marcus Institute for Aging Research and professor of medicine at Harvard Medical School. Sharon’s research focuses on delirium, a condition where older adults experience acute confusional states, commonly during hospitalizations for illnesses or surgery. Across her 32 years of research in the field she has spearheaded efforts to understand the condition and improve the quality of life of older adults, having developed an instrument to clinically identify delirium alongside different programs focused on delirium prevention. Her AAIC plenary talk will focus on the interface of delirium and dementia, and it is scheduled for Wednesday, August 3rd at 4:15pm PST. Dr. Inouye, welcome to Dementia Matters.

Inouye: I'm delighted to be here, Nate. Thank you.

Chin: Well to start, you are a geriatrician – of course I'm very excited about that – and your research focuses heavily on delirium and cognition in a hospital setting. While this doesn't seem odd to recently trained geriatricians, I do wonder if that was the case when you started your career. In essence, how did you become passionate about geriatrics and what was it that led to your investigation of delirium, which for so long was thought of as more just a field of neurology?

Inouye: So that is a really perceptive question, Nate. My answer might surprise you a little bit. I actually didn't start off in either geriatrics or delirium research, but my interest in both delirium and geriatrics evolved together. So let me tell you a little bit, going back in history, about my story. After I finished my medical training, my very first job as a medicine attending was on a general medicine service at a large teaching hospital. There, I felt so responsible as a newly-minted attending and I had on my service, over the course of those first months, six older adults who were cognitively intact on admission who became very confused during the hospitalization on my watch. I felt very responsible. This wasn't something I really had learned about during my training. And I asked all the other attendings and even my chief of service about it and they all said variations of the same thing. They all pretty much said, ‘Don't worry about that, Sharon. We see it all the time; it just happens to older people when they're in the hospital. It's not something for you to worry about.’ I couldn't stop worrying. It was really that experience at the bedside that I just couldn't stop thinking – it can't be okay, right, for older people to become acutely confused in the hospital. That just doesn't seem right. So really that's what launched me on my career as a geriatrician because I wanted to figure that out clinically and understand it more and became very engaged in the care of older adults. Then, in choosing my research topic, I kept coming back to this area of delirium. So they kind of evolved together.

Chin: Well I will say to you, your work has really influenced a lot of us at our program here in Wisconsin. It's geriatricians in the hospital that are consulted for cases of delirium and diagnosing it and how we can help people, so we are always grateful for that work. And speaking of which, you know how has research into delirium and an understanding of the condition changed over the years?

Inouye: So it's been a remarkable change, right? I've been in the field for about 32 years now. I would have to say for the first ten years I was working almost alone in the field. There were scattered people here and there, but it wasn't even called delirium when I first started. It was called acute confusional state, mental status change, acute organic brain syndrome. Nobody was consistently using that term delirium. Flash forward to now there are hundreds, maybe thousands, of people working in delirium which is wonderful and we understand a lot about delirium. There are now many tools for its identification, many ways that we understand the risk for developing delirium, and there are very effective prevention strategies. We also know its prognosis, that it leads to poor outcomes. But there's a lot yet that's still not known. We don't understand its fundamental pathophysiology and we don't have good treatments for delirium. One of the biggest things that's happened during my career in delirium – I just gave a visiting professorship at Wake Forest University. There I said that the biggest thing in delirium is that delirium really is a thing, right? It's now a thing. It's an accepted field. It's an important area of investigation. It has DSM-5 and ICD criteria. It has tools to recognize it. So delirium really is a thing and we couldn't say that thirty years ago.

Chin: And I do want to talk about your work in delirium. You created this really important tool that's very commonly used and so, for the audience's sake, how did you come to create this CAM tool that is being used in hospitals across the world?

Inouye: Yeah so, you know, I never realized that would happen. But I think when there's a need and you fill it, that's what can happen. I created the Confusion Assessment Method, or the CAM, as a tool that I wanted to be available for clinicians to use to recognize delirium quickly and easily at the bedside, and also that I could use myself in my research studies. The reason I had to do that, in all honesty because I was dragged kind of kicking and screaming into creating a tool, was that my very astute research mentors, Dr. Ralph Horowitz and Alvan Feinstein, said, ‘Oh so you want to study this area, delirium. How are you going to measure it?’ And I said, ‘Oh no problem. I'm gonna find something. I'm sure there's something in the literature. I'm gonna find it, don't you worry.’ And so I probed the literature, I reached out to people that were working in the area and I discovered to my chagrin that there was no validated tool as yet. I had to quickly develop one because I was all ready to launch my fellows project as a research fellow. So that's how the CAM was created, basically overnight, and then validated even as I started my study.

Chin: Well, I would argue too, though, it's because of your clinical experience, your clinical expertise, that you were able to put together something that is held over the test of time and is so useful both in research and in clinic.

Inouye: Yeah I was very fortunate, too, that I had a group of very smart intermedicinary experts who were willing to join me. I had other geriatricians, neurologists, psychiatrists, all with geriatric expertise, and measurement people who joined me in helping me figure out what the criteria should be, but I was very fortunate that it has stood the test of time.

Chin: Can you tell us more about how you conceptualized the multifactorial model to delirium and demonstrated that a substantial proportion is actually preventable?

Inouye: Again a really astute question, Nate. So when I thought about other common geriatric syndromes, like falls and ulcers and frailty, we know – it's widely accepted that those are multifactorial conditions. Building upon that, I really hypothesized that delirium would be the result of the interaction between how vulnerable a patient was, let's say at the time of hospital admission, and then what precipitating factors or noxious insults during that hospitalization that they were exposed to, so things like medications, procedures that have iatrogenic or adverse effects, immobilization, indwelling Foley catheters, ICU stays, sleep deprivation. All those things you can think of that might be, you know, frankly harmful to older adults during hospitalization. So I went through a series of studies. First I wanted to define those baseline factors that you could use on admission to recognize how vulnerable patients were. Then I did another study to look at those noxious insults, then I showed that they interacted. I went on to be able to kind of prove or demonstrate that multifactorial model that I hypothesized. Then we took it to the next step to see if we could prevent these factors, could we reduce delirium? And that's what we did in my next study; that was the delirium prevention trial that was published in the New England Journal in 1999.

Chin: Can you describe the Hospital Elder Life Program, HELP, that you developed and how it works?

Inouye: Absolutely. The Hospital Elder Life Program was the intervention that we designed for the delirium prevention trial that I just told you about. That was the first time it was ever demonstrated that delirium was a preventable medical condition. What we did to develop HELP was we chose six well-recognized risk factors that we identified from the previous studies that I already told you about. Those were risk factors for delirium and included cognitive impairment, immobility, dehydration, sensory impairment, sleep deprivation, and psychoactive medications. Then we targeted those risk factors with nonpharmacological, common sense interventions that could be done at the bedside. We chose interventions that we thought would be potent. In other words, they would have a big effect on those risk factors, in reducing them. And then that's what we proved worked in the delirium prevention trial, the clinical trial. Now the HELP program has been implemented in hundreds of hospitals around the world and the program is now actually overseen by the American Geriatric Society. It's a nonprofit committed to the care of older adults. They have rebranded the program as the AGS CoCare: HELP program. They really do a wonderful job and have brought in many many new sites and are mentoring them.

Chin: Is healthcare staff sufficiently trained on recognizing and treating delirium in the hospital setting?

Inouye: Yeah, it's such an important question, and unfortunately not. I think there are definitely health care systems that are ahead of the curve on this, but if you're asking me sort of as a generalization across the US or even globally I would say unfortunately not. In fact, relatively few medical schools and nursing schools actually have intensive training on delirium as part of their curriculum. Many in surveys that have been done say they had maybe one lecture on it, you know if we're lucky, maybe a bit more. Some students as you know, Nate, now do a geriatrics clerkship as part of their training, but it's not consistent. Often it's an elective or not required. As we saw during the pandemic, delirium literally became epidemic, and again I think, in large part, that was due to lack of recognition and mismanagement. Of course some of it was unavoidable, but there were many aspects that remained preventable and I think if staff were better trained on recognizing and treating delirium, it wouldn't have happened or not as severely. So things like avoiding extreme social isolation, providing communication and orientation and human touch, providing exercise, preventing immobility, avoiding the use of psychoactive drugs – which P.S. has skyrocketed during COVID – and assuring hydration and nutrition, just all the tenants – right? – of good geriatric care. Unfortunately because of the way care had to be managed, the shortage of PPE, the fear of agitated patients spreading infection and so forth, people were locked in the rooms and unfortunately not a lot of nursing care could be provided during that time. I think it really led to problems. Science hospitals who were fortunate enough to have HELP programs were able to offset a lot of that even if the help staff and volunteers weren't allowed in the rooms. They did provide education and support to the nursing staff. They did provide remote availability to answer questions, to provide communication and support for patients, and so forth.

Chin: What do you tell patients living with dementia and their families about delirium?

Inouye: That’s a really good question. So I always educate any patient that I diagnose with mild cognitive impairment or early or moderate dementia and their families about delirium, because actually it's one of the most important, preventable complications, right? First and foremost, I let them know that all drugs that they want to start, even over-the-counter, they really need to research, even check with their physicians, about whether it's associated with delirium. I caution them. Many patients don't realize antihistamines, any type of med that has sleep on it – like Tylenol Sleep or Motorin Sleep – probably has some type of sedating antihistamine in it and that can lead to a delirium. Also the H2 blockers like Ranitidine which are now available over the counter, all the anti-ulcer meds. I let them know that any classes of these types can lead to a delirium and they're always so shocked because you can just walk into a drugstore and get them. And so I always tell them please, please contact me before you start a new med. Also if they're going into the hospital or in for a scheduled surgery, I urge them to make sure that they let both their surgeon and anesthesiologists know that they have this cognitive diagnosis – MCI or dementia – and ask them to take precautions in the anesthesia they use, the medications they use pre-op and post-op, and make sure that they're not going to aggravate the confusion. Of course if I'm speaking to the surgeon or the anesthesiologist, I do ask them to keep their meds short-acting and avoid anticholinergics. I also urge them to make sure they bring in their med list, the name of their pharmacy, any over-the-counters that they are taking, and also to give the doctors – the surgeon and the anesthesiologist – the names of all their doctors and their phone numbers. If my patients let me know in advance that they're going for surgery or scheduled hospitalization, I make sure we review together everything they can do to minimize their cognitive risk, things that they can do like exercise, reduce alcohol, stop smoking, really get good sleep, etc, to try to build them up as much as possible.

Chin: Your upcoming plenary talk at AAIC will focus on your research findings on this interface between delirium and dementia. Can you give our listeners a brief summary of the topic and explain any background or concepts that they should be aware of before they tune in to watch?

Inouye: Oh sure, happy to. In my talk, I'm hoping to provide an overview of the very strong and robust, yet very complex interrelationship between delirium and dementia. It's an area where we have a lot of evidence and yet there are many uncertainties. There's many lines of evidence, for example, epidemiologic evidence that shows that each condition, delirium and dementia, they're both risk factors for each other. For instance, people with delirium appear to be at higher risk of developing a subsequent dementia, and vice versa, people with a dementia seem to be at higher risk – four to five-fold, in fact, increased risk – for developing delirium during a hospitalization. They also share common pathophysiologic pathways and biomarkers; I'm going to overview that during my talk. They share common mechanistic pathways as shown in mechanistic molecular and animal studies. The big question really is whether delirium itself leads to dementia. There, you know, the question largely remains unanswered. So I'm going to talk about those areas of uncertainty and what really would be needed to establish a causal relationship – like what types of studies in the future.

Chin: It's gonna be a fascinating talk and so I encourage all of our listeners to tune in. To end, what topics are you looking forward to hearing at AAIC this year?

Inouye: Absolutely! Well I'm really excited – as everyone else is I'm sure – to learn about the latest advances in therapeutics and treatment. There's been so much about Aduhelm and I know there's many, many other treatments on the horizon, and so I want to learn all the latest. Also there's a lot of work going on in advances in earlier diagnoses, identifying people who are on that pathway of developing AD and related dementias and how we can identify them earlier in their course where they could be more amenable to treatment. Also another big area of interest for me is support for family and informal caregivers. You know, this is not going to go away even as we develop better treatments. We are always going to need to find ways to help and support families and caregivers, so I'd like to learn the latest research and the policy work that's happening in the field.

Chin: Well thank you, Dr Sharon Inouye, for giving us this introduction to your plenary talk, that will be happening later on Wednesday, August 3rd at 4:15 PM Pacific Time. We do hope to have you on again in the future.

Inouye: Thank you, Nate. This was just wonderful, I really appreciate it.

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 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 Thanks for listening.