Evaluating and Managing Lewy Body Dementia

Podcast Transcript

Dr. Alex Rae-Grant: Neuro Pathways, a Cleveland Clinic podcast from medical professionals exploring the latest research discoveries and clinical advances in the fields of neurology and neurosurgery. Welcome to another episode of Neuro Pathways . I'm your host, Alex Rae-Grant, neurologist in Cleveland Clinic's Neurological Institute. In an effort to explore the latest advances in neurological practice, today, we're discussing Lewy body dementia, evaluating and managing the disorder. Dr. Jim Leverenz, director of the Lou Ruvo Center for Brain Health in Cleveland, Ohio, Jim, welcome to Neuro Pathways.

Dr. Jim Leverenz: Thanks for having me.

Dr. Alex Rae-Grant: Jim, I know you're not a native Clevelander. Can you tell our listeners where you're from, where you trained, and when you began your career at the Cleveland Clinic?

Dr. Jim Leverenz: Sure. So it's a little complicated. My family's actually from the Cincinnati area of Ohio, but my father decided to go work for Boeing when I was a very young child. And we moved to Seattle where I pretty much grew up, did my undergraduate and medical school there. I knew right from the beginning of my medical school career and even as an undergraduate, I was very interested in the brain and disorders like Lewy body dementia and Alzheimer's disease. And so after medical school, I went back east to New York and trained at the New York Hospital in neurology and then University of Chicago for geriatric neurology and neuropathology and then went back to Seattle and thought I'd be there for the rest of my career. And then about five, six years ago, the Cleveland Clinic called and made me an offer I couldn't refuse to set up a program here in Cleveland. We already had one in Las Vegas. And here I am five years later enjoying my time here at the Cleveland Clinic.

Dr. Alex Rae-Grant: That's great and charging right along too.

Dr. Jim Leverenz: Charging right along.

Dr. Alex Rae-Grant: The first step in understanding Lewy body dementia is ensuring that we're all using the same terminology. Can you define this disorder for us?

Dr. Jim Leverenz: Sure. I usually like to start with saying that we hear a lot of different terms, and we often hear from our patients these questions and from families. So what I start with is, what's dementia? And dementia usually means you have a change in your thinking skills, that it's affected in some way your day-to-day functioning. Some of you may have heard of mild cognitive impairment, which means that you have a change in your thinking skills, but you're still maintaining most of your normal day to day activities.

What I like to call the Lewy body dementias are the two main kinds of dementias that we see linked to Lewy body pathology that we see in the brain at autopsy. The one most people are familiar with is starts with a dementia and often has characteristic changes like hallucinations and parkinsonism, motor parkinsonism. But what people often don't understand, the other half of that Lewy body dementia picture is the Parkinson's disease dementia. And for many years, we didn't think Parkinson patients got a change in their thinking skills, but as the disease progresses, that turns out to be a much bigger issue than even the motor symptoms that they have. So we have two Lewy body dementias, one that starts with a cognitive change and one that starts mostly with a motor change. After a number of years, they can look very much alike.

Dr. Alex Rae-Grant: So let's talk about the diagnosis of Lewy body dementia that is more traditionally understood. What are the current criteria to try to make that diagnosis clinically?

Dr. Jim Leverenz: So the criteria been revised over a number of years. The latest published in 2017 in neurology really focused on the classic symptoms that we see. First of all, person has to have a dementia as we defined it earlier and then four core symptoms. So there's the visual hallucinations that everybody understands and hears about, parkinsonism, usually motor parkinsonism, less often the classic asymmetric resting tremor we link to Parkinson's but more slowed stoop posturing, shuffly gait, fluctuations in which a person will have good days and bad days, and I often ask that simple question, and then something called REM sleep behavior disorder where they act their dreams out at night. And that's been very strongly linked to having Lewy body changes in the brain.

What's been added recently is the idea that you could have this dementia with Lewy bodies that presents with dementia with one of these core symptoms besides dementia with a biomarker. And the biomarkers typically are the REM sleep disorder documented in a sleep study. So something as a neurologist for example, if you hear about a sleep study, you may want to double check. Sometimes, it's varied in that sleep report and then a dopamine scan, a DaTscan which can show a reduction in the dopamine input into the striatum. Typically used in Parkinson's but actually when it's positive, can be very helpful in a dementia patient. There is a cardiac adrenergic input study that we typically don't do much in the U.S., but it's very common to do in Japan.

Dr. Alex Rae-Grant: How would that differ from Parkinson's disease dementia, dementia merging in a more typical Parkinson's syndrome?

Dr. Jim Leverenz: Well, the consensus at this point is that if your dementia kicks in within a year of onset of your motor symptoms or precedes the motor symptoms that we classically link to Parkinson's, then it is a dementia with Lewy bodies. If somebody has classic Parkinson's, you have a patient you've been following, they started with a resting tremor, they were doing very well on therapy, and five, six, 10 years into it they start developing cognitive issues, then that's Parkinson's disease dementia.
They both at autopsy, when we look in the brain, have these Lewy body inclusions, and as a part time neuropathologist as well, I can tell you I can't under the microscope say did this person start with Parkinson's motor symptoms or did this person start with a dementia or hallucinations or one of these manifestations.

Dr. Alex Rae-Grant: You've seen a lot of people of this type, and what are some of the core clinical things that you hear from patients and families that gets you thinking about the Lewy body dementia idea? I mean, what really triggers your thought process in that?

Dr. Jim Leverenz: Well, typically what I'll get is number one, I'll watch them as they walk into your office. I used to work at the VA when I was in Seattle, and people would, when I'd ask them to walk for me, they do a military mark walk down the hall, and then as I see them leaving, I see them stoop, shuffly. The classic dementia with Lewy bodies, people who start more with a cognitive change, they'll be more subtle. They won't typically have a resting tremor or asymmetric. They'll just be a little stooped, a little slow, and that may come and go. That may fluctuate.

The other thing that I've noticed over the years is they don't typically have the memory loss that you would think about with Alzheimer's. So you would need to find out what kind of symptoms they're having. They tend to have more insight. Occasionally, they're the ones that bring themselves in and say, "Something's not quite right. I'm struggling keeping up during the board meeting," or whatever.

And you have to ask about the REM sleep disorder, which is acting out your dreams. And usually, you have to have, right, a bed partner because you're asleep and dreaming during this. And the families will go, "Oh, I didn't know that was important. But yeah, he yells, screams, falls out of bed. He hurt himself once," that sort of thing. To document that, you really need to have a sleep study.

And then to ask about hallucinations, I've been shocked at the number of times I've asked somebody, "Do you ever see children, animals, other animate objects?" And the patient will say, "Yeah, I do. I always see these little kids," and the spouse will look at me and say, "They've never told me that." He goes, "Well, it wasn't bothering me, so I didn't mention it." And that's also something that I sometimes see. They're not frightening oftentimes, at least initially like we would see in say schizophrenia or people saying bad things about you. Occasionally, that's the case. But usually it's small people, small animals. There's always a dog. Sometimes the family will say, "We knew something was wrong when he said, 'Set the table for those three people sitting in the corner.'" And many times, the patients will laugh. They'll say, "I know it's not real." I had one person say, "Every morning I look out in the backyard, and there's a Mariachi band out there, and I know there isn't a Mariachi band in my backyard."

Dr. Alex Rae-Grant: It's interesting. They're aware of the non-reality of the hallucinations.

Dr. Jim Leverenz: It can be, and in that circumstance, I often won't be aggressive about treating the hallucinations. Although I would say it tells you, you have to ask the question, and it often tells you something, the patient would never think that maybe it's important I mention this to somebody.

Dr. Alex Rae-Grant: So you have obviously a large practice of people with both forms of Lewy body dementia. Can you tell us what the typical course of treatment is? I mean, how would you approach treatment for these two types of dementia?

Dr. Jim Leverenz: Well, number one, I think it is important to do your usual dementia workup, which is make sure that the blood work is normal. I will get up an image of some sort, usually an MRI if I can. And here at the Cleveland Clinic, we have the volumetrics available to us, so we can measure different parts of the brain. Traditionally, these patients often don't have a whole lot of brain atrophy and then a good physical examination, asking these pertinent questions that we mentioned.
If everything else looks pretty good, then I usually will start with a cholinesterase inhibitor, the donepezil, the rivastigmine, the galantamine. There is data. In fact, rivastigmine I believe is approved for Parkinson's disease dementia, but we often, most of us in the field recognize that these patients often do better than my Alzheimer patients too with these medications. They help with that ability to stay on track cognitively. And there's some limited evidence that it helps with reducing hallucination frequency and severity.

Dr. Alex Rae-Grant: What about using traditional Parkinson's medicine for the dementia problem? I mean, does that help?

Dr. Jim Leverenz: It doesn't generally help the dementia, but we do see patients who respond to the therapy motor wise. And I see a variety of responses over the years, so some people have more hallucinations. I would say I've been drifting a little bit more towards giving it a trial if they're having significant parkinsonism that's affecting their day-to-day life but giving the family and them a warning that this could increase things like hallucinations.

Dr. Alex Rae-Grant: Speaking of the family, is there anything else that you do in the Center for Brain Health to help the families out? Is there any other things we can do to help them with caring for a person with dementia?

Dr. Jim Leverenz: Well, sometimes it's just letting them know what's a part of the disease and what's part of something else that they should be wary of and that these patients can vary. I think the toughest question I get is we have some patients who fluctuate pretty dramatically, and they've been to the ER three or four times where they were tough to wake up, they were very confused, and then the whole workup is negative, and they go home. And is this a some sort of significant event, or is this a part of the fluctuations and giving them some advice at least that that can happen much like you see motor fluctuations in Parkinson's disease.

Dr. Alex Rae-Grant: So Jim, what about the use of antipsychotics in people with dementia? What would you say about that?

Dr. Jim Leverenz: Well, certainly we see the, as I mentioned, the visual hallucinations in the Lewy body dementia patients. And typically, if they're not bothered by them, then I don't treat them. I don't know if I like to use the term sometimes with my trainees, "happy hallucinators", and sometimes patients thinks that funny. Sometimes, they don't. But if they're not bothering then I try not to treat them.

The other thing as I mentioned earlier is the cholinesterase inhibitors like the donepezil, the rivastigmine, the galantamine can be very helpful in reducing the frequency of hallucinations. When I typically have to use them is when people are having delusions associated with them, so they believe they're real, and they're calling the police, or they're running out into the streets, that sort of thing.

I always explain to families and patients that those have significant downsides, right? They're sedating typically. But I would say most of us in the field have been using quetiapine, which we don't have clear evidence that it helps, but it's our clinical experience and doesn't have the negative side effects that you would think with a traditional haloperidol and those kinds of traditional antipsychotics. There is pimavanserin, which has been approved for Parkinson's associated psychosis. And we're certainly interested in looking at that kind of medication further for treating hallucinations more safely in these individuals.

Dr. Alex Rae-Grant: We've made great strides in dementia in general. Can you tell us about the latest research both in the field and also the work that you and your group are doing?

Dr. Jim Leverenz: Sure. We just had actually an international Lewy body dementia meeting in Las Vegas and really brought the world's experts together, and I think the big focus has been on looking at these individuals over time. What does it tell us when we see a dopamine transporter scan, for example, the DaTscan is negative in somebody we think has Lewy body dementia?

Some of the treatment questions you asked, what we're seeing is a lot of variability. Some patients seem to progress fairly rapidly, and other ones it seems as if it goes for a very long time. And some Parkinson patients, it's very uncommon, but 10, 15 years really haven't had a whole lot of cognitive change. The big focus I think right now is, how do we use these biomarkers, the blood, the spinal fluid, the genetics, the imaging, to define patients and figure out better ways to treat them, and who should be treated with which particular medications?

At the Center for Brain Health here in Cleveland, we have a couple of studies now focused on that, clinical trials. We also have what we call a Dementia with Lewy Bodies Consortium, and this is a nine site consortium led by us here in Cleveland looking at patients longitudinally over time, very detailed evaluations but really trying to see which evaluations work best for predicting how people are going to do and ultimately, how they would best respond to disease modifying therapy.
And we also just awarded an Alzheimer's disease center, but one of the focus there is on Lewy body dementia as well. So we're very excited about the opportunities and how the work begins.

Dr. Alex Rae-Grant: So if somebody was interested in being involved in the research you're doing, is there a way that they can get connected with that?

Dr. Jim Leverenz: So they can call the Center for Brain Health here in Cleveland, and our number is (216) 445-9009, or they can email us at cbhresearch@ccf.org.

Dr. Alex Rae-Grant: Well, Jim, thanks so much for joining us. I really appreciate your time and insights.

Dr. Jim Leverenz: Thanks, Alex, very much.

Dr. Alex Rae-Grant: This concludes this episode of our Neuro Pathways podcast. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast. Subscribe to the Neuro Pathways podcast on iTunes, Google Play, Spotify, SoundCloud, 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, consultqd.clevelandclinic.org/neuro or follow us on Twitter @CleClinicMD, all one word. That's @ C-L-E Clinic M-D on Twitter. Thank you for listening. Please join us again soon.