Neuropsychiatric Symptoms in Dementia

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: February 15, 2025
Expiration Date: February 15, 2026

Estimated Time of Completion: 30 minutes

Neuropsychiatric Symptoms in Dementia
Dylan Wint, MD

Description
Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

• Review up to date and clinically pertinent topics related to neurological disease
• Discuss advances in the field of neurological diseases
• Describe options for the treatment and care of various neurological disease

Target Audience
Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.

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• American Medical Association (AMA)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
  
  Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

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  A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

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  Successful completion of this CME activity enables the learner to earn credit toward the CME requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

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Podcast Series Director
Andreas Alexopoulos, MD, MPH
Epilepsy Center

Additional Planner/Reviewer
Cindy Willis, DNP

Faculty
Dylan Wint, MD
Lou Ruvo Brain Health Center

Host
Glen Stevens, DO, PhD
Cleveland Clinic Brain Tumor and Neuro-Oncology Center

Agenda

Neuropsychiatric Symptoms in Dementia
Dylan Wint, MD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Andreas Alexopoulos, MD, MPH, Cindy Willis, DNP.

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: Neuro Pathways Podcast February 15, 2025 to log into myCME and begin the activity evaluation and print your certificate If you need assistance, contact the CME office at myCME@ccf.org

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Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD: It is estimated that 90% of individuals with dementia also experience neuropsychiatric comorbidities significantly impacting their quality of life and that of their caregivers. For providers, understanding these symptoms is paramount to providing comprehensive care for patients.

In today's episode of Neuro Pathways, we're discussing the different neuropsychiatric disorders present in dementia, address potential medical and environmental contributors, and aim to equip you with the knowledge to manage these challenging symptoms effectively.

I'm your host Glen Stevens, neurologist/neuro-oncologist in Cleveland Clinic's Neurological Institute. I'm very pleased to be joined by Dr. Dylan Wint. Dr. Wint is a behavioral neurologist and neuropsychiatrist and the medical director of the Cleveland Clinic. Lou Ruvo Center for Brain Health in Las Vegas, Nevada. Dylan, welcome to Neuropathways.

Dylan Wint, MD: Thanks for having me, Glen.

Glen Stevens, DO, PhD: So Dylan, before we start, why don't you tell us a little bit about yourself, your background, how you made your way to Las Vegas.

Dylan Wint, MD: I was in medical school when I had an epiphany that the brain was probably the place to go if I wanted to help people feel and function better. In my neurology and psychiatry training, I saw folks who had pretty healthy bodies and yet if their brains were diseased, they had pretty miserable lives. And conversely, people who had really devastated physical statuses, but if they didn't have depression and they were cognitively intact that they were quite happy and content. And so thought the best way to approach healing was to approach it sort of head down. And so I trained in psychiatry and neurology and then did some research at NIH and did some further research at Emory. And then this opportunity opened to take care of folks with degenerating brains in Las Vegas working with the Cleveland Clinic. And I couldn't pass up the opportunity.

Glen Stevens, DO, PhD: Well, we're glad to have you on board and I'm waiting for my epiphany here.

Dylan Wint, MD: I'll try and give you one today.

Glen Stevens, DO, PhD: Okay, so let's start broad. What are the most common neuropsychiatric symptoms associated with dementia?

Dylan Wint, MD: So, in people with relatively mild dementia, the most common symptoms we see are depression, apathy, and irritability. Sometimes anxiety. As dementia progress, we tend to see more severe symptoms like agitation, aggression, hallucinations, and delusions. This varies somewhat depending on the specific type of dementia. So for example, dementia with Lewy bodies is notorious for, and in fact, one of the diagnostic criteria is visual hallucinations, which can occur very early, can even be the very first symptom. So there's sort of this broad description of which symptoms occur early and late, but it does depend on the specific type of dementia.

Glen Stevens, DO, PhD: And maybe a difficult question to answer, but the underlying etiology of these neuropsychiatric symptoms…

Dylan Wint, MD: The most straightforward answer I can give is that because behavior originates in the brain, a degenerating brain is likely to produce abnormal behaviors. But there are also I think some meta effects of the cognitive component. So for example, if you are highly forgetful and your spouse tells you that they are going out, you forget that they're going out, they come back three hours later, you in the meantime been wondering where are they? Why didn't they tell you where they were going? You can be pretty agitated and irritable by the time that loved one gets home. And so I believe that the cognitive dysfunction can sometimes contribute to the behavioral symptoms perhaps as much as the actual physical degeneration and neurochemical degeneration of the brain itself.

Glen Stevens, DO, PhD: How common is agitation and aggression – as you just sort of mentioned in that scenario?

Dylan Wint, MD: Agitation occurs in at least 25% of people with dementia. And as dementia progresses, we start to see numbers more like in the 40 to 60% range of people with dementia that exhibit agitation.

Glen Stevens, DO, PhD: And what percentage of, and again, I know it'll vary a little bit by the phenotype, but discussion of delusions and hallucinations, the difference between them and how common?

Dylan Wint, MD: So delusions are an abnormality of thought content. So delusions refer to a belief that is provably untrue and yet firmly fixed in the individual's brain. Hallucination is a perceptual disturbance. So the person is experiencing a perception that does not have a correlate in objective reality. So seeing something that's not there would be a visual hallucination. We can see hallucinations and delusions in as many as 15% of people with early Alzheimer dementia. We can see hallucinations in as many as 50 to 60% of people with early Lewy body disease. Interestingly, in frontotemporal dementia hallucinations tend to be relatively unusual unless you have a specific subtype of frontotemporal dementia. But the rates increase pretty significantly so that by the time someone has severe Alzheimer dementia that they've had, hallucinations is over 50%. The likelihood that they've had delusions is at least 40%.

Glen Stevens, DO, PhD: So, I was having a discussion with one of the residents yesterday, and we actually were discussing Capgras syndrome, which I guess is a form of delusion. And I was telling her about the movie Invasion of the Body Snatchers, which is a very old school movie, had Donald Sutherland in it. And again, it's sort of that same theory where someone they know has been replaced. And in this case, I guess it really wasn't a delusion because it was true that people were being replicated. But do you see Capgras syndrome itself? I guess it's kind of a form of delusion, right?

Dylan Wint, MD: It is a form of delusion, specifically in a category of delusions known as misidentification syndromes, where the person with the syndrome either thinks that a loved one has been replaced by an imposter or that a loved one, not necessarily a loved one, but a specific individual is inhabiting the bodies of many other people. So it can actually happen either way, and it's probably related to dysfunction in a specific area of the right hemisphere.

Glen Stevens, DO, PhD: And as you can imagine, would be a pretty difficult living environment if your spouse doesn't believe you're who you say you are, would be pretty complicated.

Dylan Wint, MD: It is one of the most devastating things that happens for a caregiver when their spouse or their parent or their child no longer recognizes who they are or disconnects who they are from the emotional relationship that they've had over the years. So it's fundamentally a destruction or reversal of that relationship that typically has been going on for many decades.

Glen Stevens, DO, PhD: So just sort of moving down the continuum here, what about paranoia? How common is it? Problems related to it?

Dylan Wint, MD: Yeah, paranoia is another delusion, or at least preoccupation where someone thinks that others intend to hurt them. And we do see this quite commonly. Sometimes it's relatively subtle refusal to take medications because, well, I don't remember the doctor telling me. If someone is not paranoid and their spouse tells them, these are the medicines the doctor suggested you take, typically they'll go along with it. But a subtle paranoia can be exhibited by that refusal. And then there can be more intense paranoia, literally saying that a loved one or a caregiver is out kill them or to harm them purposely. It's one of the more common delusions, I'll put it that way. And I see it quite a lot. I don't know the specific percentage, but it is a frequent occurrence. And I think that in some situations, this is also related to the cognitive aspect. You don't remember your doctor telling you to take that. Why is your loved one trying to push it on you? Yeah, you said that you told me you were going out, but were you really? Or did you really tell me that? I don't remember you telling me that. If you're in a world where that's constantly filled with uncertainty and gaps, our tendency as human beings really is to fill those gaps generally with the information that's most likely to keep us safe. If you're in the woods and you're in the dark woods and you hear a branch crack behind you, you don't typically think, oh good, my friend is here. Or oh, it’s Ed McMahon with my $10 million sweepstakes prize. Our automatic thought is that there may be some danger around us. So in the absence of information, our tendency is to fill in with what will keep us safe. If we make a mistake of hypervigilance, in other words, thinking we could be harmed and we're wrong about that, it's unlikely that we're going to come to any negative physical consequence. Whereas if we make the mistake of hypo vigilance thinking everything's all right and we're wrong about that, it could be fatal.

Glen Stevens, DO, PhD: Yeah, well explained difficult of course, to deal with the other thing that we see. But wandering is a big problem, I guess in demented patients. Well, can you discuss that a little bit?

Dylan Wint, MD: Yeah. There are all kinds of reasons really that people wander, we think. So one may be simply agitation, excessive physical activity that doesn't necessarily have a purpose. But if you are agitated and part of your agitation is pacing and there's an open or unlocked door, that pacing might lead you out of that door. And without the cognitive wherewithal to get back to the door you started from, you'll end up lost.

The memory issues are also a problem. Imagine that you look around and you're not sure where you are or how you got here because you don't remember. The instinct is to try and find something or someone familiar. And sometimes when people are lost or almost lost, we can get enough out of them to understand that they were looking for my wife, my child, or whatever. Sometimes the memory issue is severe enough that people are looking for things like their childhood home or they're 80 something years old and they're looking for their parents because that's the last safe thing that they can remember.

And then sometimes it can be anxiety or fear that if they’re paranoid, if they're worried that something in their immediate environment is going to be harmful to them, then they do what any of us would do with that information. We try and get away from that potential harm.

And then sometimes it's just someone who hasn't been identified as having a memory problem yet is going about their usual activities, whether it's walking to the corner store to grab a Coca-Cola or they go to drive to their hairdresser and they become lost, confused, continue trying to find their way back. And what they do is really find their way farther and farther away from safety.

Glen Stevens, DO, PhD: Can you use behavioral modification to fix this or it's not helpful?

Dylan Wint, MD: Behavioral modification can be helpful. It's a bit unpredictable because the source of the wandering can be difficult to overcome. So for example, if someone is simply afraid for their lives and that's why they've left the house, behavioral modification is not likely to overcome that because we're talking about an existential threat. If it's something more along the lines of unfamiliarity and a desire to go home, there may be ways to settle down that patient, make sure that they understand that they're in a safe location with a safe person and repeatedly reassuring them of that emotional safety can sometimes overcome the cognitive response, which is, I don't know where I am and I should get to someplace that I recognize.

Glen Stevens, DO, PhD: So, a lot of neuropsychiatric comorbidities. I'm sure there's a lot of daily medications that people can take that can even worsen some of these. How do you go about trying to figure out, are we doing something negative that's worsening this underlying comorbidity?

Dylan Wint, MD: That's not incredibly easy, but there are a few general rules. So medicines that have sedating or amnestic effects. So those would be benzodiazepines which have amnestic effects, antihistamines which are sedating, and then medicines that have cognitive adverse effects such as anticholinergics, particularly in the elderly. We definitely try and avoid using those and try and eliminate them if they're on board. And there are all kinds of reasons these medicines are used, right? So antihistamines are not just used for sedation anxiety, they're used for allergies, they're used for GI situations, anticholinergics of course for bladder and GI issues. So we try and eliminate those medications. We have to think about also whether there may be something medically going on with the patient, something physiological, particularly if the behavioral change developed relatively rapidly and is accompanied by an increased degree of confusion or general dysfunction. So we go about that almost in the way we would do a delirium evaluation – look at their medicines, understand which are CNS central nervous system penetrate medicines, the ones that are central nervous system penetrators that have those adverse effects, we try and eliminate them, and then we look for information that suggests something else physiologic may be going on.

Glen Stevens, DO, PhD: So it's a big list of comorbidities, treatment options for them. And again, I'm sure it varies depending on which one it is in particular, but what type of options do we have?

Dylan Wint, MD: So there are not many FDA approved options. The FDA has approved brexpiprazole, which is a dopamine modulator, I guess you'd call it for agitation and aggression in Alzheimer's disease. It does seem that it can have some effectiveness in other conditions, other dementias as well. And it's near relative aripiprazole has some pretty good data, although it's not approved by the FDA for the purpose. For psychosis, delusions and hallucinations in Parkinson disease, pimavanserin or NUPLAZID® is FDA approved. For pseudobulbar affect, which is the old term for it is emotional incontinence, dextromethorphan and quinidine, which is also called NUEDEXTA®, is approved. And then sort of looking at things that are not FDA approved but have some efficacy, there are data indicating that atypical antipsychotics can be effective for verbal and physical aggression, but all antipsychotics do have the risk of increasing the rates of sudden death of stroke in people with dementia. So they have to be used with caution, and we want to use them only in situations where there is some risk to the patient or another individual. Serotonin selective reuptake inhibitors, so typically use this antidepressant or anti-anxiety agents, can sometimes be helpful for agitation and irritability. Citalopram does have a large well done study demonstrating some benefit at 20 milligrams. At 30 milligrams there was benefit, but also QT prolongation and actually for unclear reasons, cognitive worsening.

I would say that in broad categories, serotonin reuptake inhibitors can be useful for irritability, anxiety, depression symptoms and aggression. That anti-psychotics can be useful for agitation, aggression, and of course hallucinations and delusions, and we shouldn't forget that there are behavioral modifications that can be useful as well.

Glen Stevens, DO, PhD: So before we go to the behavioral modifications, I was reading earlier, I think that apathy is very, very common in Alzheimer's patients and that the acetylcholinesterase inhibitors can be helpful for the apathy. Would you agree with that? Do you see that or you don't agree?

Dylan Wint, MD: There is real data suggesting that as a secondary outcome in some cognitive trials of cholinesterase inhibitors. I have seen people get improvements in apathy or reduction in apathy with cholinesterase inhibitors. It's almost never been when I've used them for that purpose. So I have applied these to folks who have mild dementia and the patient and their family return and say that they've been much more active, much more tuned in. But when I prescribed it specifically, hoping for that effect, I really haven't seen them. So they do have an impact. It's beyond me to predict in which patients,

Glen Stevens, DO, PhD: Now of course patients have common agitation, aggression, but also apathy. So what about use of the stimulants, methylphenidate, those types of things? Does it worsen the agitation or does it help the apathy? Or again, in your experience, have you seen much benefit?

Dylan Wint, MD: I have used methylphenidate to treat apathy. It's really the only agent that I know of that as a primary outcome in a study specifically for this has shown benefit over placebo, but that wasn't a high amount of benefit compared to placebo. I think it offered about a 15 to 30% superiority over placebo. So although it's more likely to work than placebo, it's less likely to work than not. And sometimes I've seen benefit anecdotally in my patients, I probably have not used a stimulant in someone who had both apathy and aggression because of what you imply that a stimulant may make things worse. So I wouldn't be able to comment on that, but it would be a concern.

Glen Stevens, DO, PhD: And you alluded to it a little bit, but behavioral or non-pharmacologic approaches that you utilize? Can you comment on those?

Dylan Wint, MD: Yeah. So one of the most effective is actually caregiver education in terms of their own understanding of the behavior and reaction to it. So one of the things that's very important for caregivers is to try as hard as possible, although it's difficult to avoid taking these things personally to understand that this is not coming from the person you knew, but it's coming from that person being driven by and also filtered by a disease that we understand very little and that because all of our behaviors come from our brain, when we see that cognition has been impaired in a brain, we can almost expect that behavior will be impaired also. So just knowing that it's part and parcel of this syndrome that we refer to as dementia, but intend to talk about primarily in cognitive terms, sometimes that's really helpful, just that understanding.

A second is helping the caregiver to understand that the source of a lot of these behaviors is really absence of information and a response that is fearful and self-protective. So he won't take his medications and going through not remembering that the doctor said to take them or believing that you're still capable of taking them and try and assist the patient in what they're doing as opposed to order them to do things. And then behaviorally for the patient exercise. So it turns out that keeping people active tends to reduce behavioral problems, particularly aggression. So the more that you're able to keep them moving in a programmed fashion, the less likely they are to act out. Outdoor activities seem to be particularly helpful, cognitively stimulating activities and then social interactions, so keeping the mind engaged with conversation or other social activities. And then they're sort of behavioral plus physical. So massage and touch therapy also seem to reduce depression symptoms and agitation.

Glen Stevens, DO, PhD: I really like the education part of this. I think we spend a lot of time with our patients in the tumor field of educating because it’s the fear of the unknown. And if you can educate individuals, caregivers as to what's likely to happen, what's reality isn't, why is it happening? Even if you can't change it, then you at least empower them and they can deal with it a little bit better. But I'm sure it's very difficult. My parents both passed away when they were young, so I didn't go through this with my parents, which again is always the good news, bad news aspect of it. But certainly out there, many do and caregiver – very, very difficult. I applaud people that are able to give the care that's required for this, and I think the onus is on us to support them.

Dylan Wint, MD: Agreed. Agreed.

Glen Stevens, DO, PhD: And I think that it can be difficult for everybody involved, but I like hearing what you guys are doing. How effective do you think all these strategies are for patients? Or when does a patient need to go into a facility?

Dylan Wint, MD: That is a great question. I would put it this way that as with any other medical intervention, any other intervention for a medical issue, there are going to be some people who respond better than others. And as for most chronic conditions, treatment from multiple angles. So it doesn't have to be a behavioral intervention or a medication, and it doesn't have to be an SSRI or an atypical anti-psychotic, but as one of my mentors used to say, take as many shots on goal as it takes to try and improve things. The way that I approach talking about placement, first of all, try and put myself in that individual's position. And then I think about what the health consequences might be for being a caregiver. So one of the primary ones is simply lack of sleep. Patients who wander, patients who have insomnia, their caregivers are up with them, and that lack of sleep is going to have consequences for the caregiver. And just like we have rules for how long residents can work, and just like there is no job that anyone has where they're on duty 24 hours a day, seven days a week, if we are seeing a caregiver who's in that situation, we really have to think about intervention, which may include placement if we've tried those other things. And then what does the caregiver look like when they show up at the office? Are they very resigned? Are they in a situation where it seems like they become apathetic as well? That may indicate that they're at the end of their rope. Or toward the other end, severe distress or severe irritability on the part of the caregiver may also indicate that for their health and really also for the patient's health, it may be time to think about an alternate living situation or care arrangement.

Glen Stevens, DO, PhD: So, I probably shouldn't admit it, but several months ago we went to go see the notebook, and of course it's a movie about a woman with dementia and the husband comes to read the story of their life with her. And I think my wife has this idea that if she gets demented, I'll come and bring all the photo albums that we have and it'll pull her out of it as it goes through. But I think in some ways it's a good depiction of what families go through because it sort of goes through the various stages of she knows him, she doesn't know him, she's there, she's not there, she's angry, she's not angry. And you can really see how it tugs at the caregiver and just not quite sure how to respond in these situations.

Dylan Wint, MD: I haven't seen it myself. Maybe I shouldn't admit that.

Glen Stevens, DO, PhD: So research wise, anything that we should know about that you guys are working on?

Dylan Wint, MD: As few FDA approved treatments as there are so far for these behavioral conditions in dementia, people are constantly working to try and come up with better treatments. So there are numerous clinical trials in the works of various medications, most of them that operate on serotonin or dopamine to try and help with these conditions. Because even as we have now the advent of disease modification in Alzheimer's disease, there are still millions of people for whom disease modification is not going to work at all because they're at a stage beyond expected benefit. And even the disease modification we have so far, as far as we can tell, people are still going to progress. So we're still going to need behavioral interventions. The best reassurance I think I can give is that people are constantly working on this problem or this set of problems, and that we expect to see more and more treatments either approved or at least demonstrated to be effective for managing these behaviors.

Glen Stevens, DO, PhD: Well, Dylan, I'd like to thank you for taking the time to join us today and share your expertise and look forward to having you back in the future. So thank you very much.

Dylan Wint, MD: It's my pleasure. Thank you for having me.

Closing: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.