James Galvin, MD, MPH, is a Professor and Associate Dean of Clinical Research at Charles E. Schmidt College of Medicine, Florida Atlantic University, talking about Lewy Body Disease and a new trial study that tries to tackle the issues of this disorder.
Interview conducted by Ivanhoe Broadcast News in May 2017.
Can you tell me what is Lewy Body Disease and how many people are affected by that?
Dr. Galvin: Lewy Body Disease describes a group of disorders that share in common, a collection of abnormal protein in the brain called a Lewy body. There are several diseases that fall under Lewy Body Diseases. The first is Parkinson’s disease, which is largely a movement disorder. A large portion of people with Parkinson’s disease will develop Parkinson’s disease dementia. These are people who start out with motor Parkinsonism with slowness in movement, balance problems, falls, tremors and they eventually develop cognitive problems. The other type of disease is called dementia with Lewy bodies and so these are people who will start off with any other presentation besides the Parkinson’s. They might start off with a dementia, a sleep disorder, or a behavioral disorder. Then they may develop Parkinson’s-like symptoms with the motor symptoms. It’s really a combination and so Lewy Body Dementia encompasses all of those diseases: the Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies. The main difference is what came first. If they have Parkinson’s disease first and then develop the cognitive behavioral problems, it’s Parkinson’s disease ementia. If they have any other combination, it’s dementia with Lewy bodies. So PD plus PDD plus DLB equals LBD. It’s a little mathematical formula essentially. Parkinson’s disease, Dementia, plus Dementia with Lewy bodies make up the group of Lewy Body Dementia.
Is this disease prevalent and is it difficult to diagnose? Are people going from doctor to doctor to finally get a diagnosis?
Dr. Galvin: Like many neurologic diseases, it’s very hard to get an exact number. But using all the best estimates that we can, a group of investigators and the Lewy Body Dementia Association were able to derive estimates of disease. Then we estimate if there are approximately 1.3 million Americans who have Lewy Body Dementia, this would make it the second most common primary degenerative dementia after Alzheimer’s Disease. We estimate Alzheimer’s has about 5.3 million Americans, Lewy Body Dementia about 1.3 million Americans. It’s probably the most common disease you’ve never heard of. Which gets to the second part is that it’s a rather difficult diagnosis to make because some of the symptoms are difficult to elicit during a regular conversation. You have to ask the right questions to get the right answers. We actually did a study of over 900 caregivers of patients with Dementia with Lewy bodies and what we found was roughly at eighteen month period in delay in diagnosis where people had to see multiple doctors over multiple visits. About fifty percent of the time the initial diagnosis was wrong. The diagnosis then later on had to be established by a neurologist in about sixty percent of cases.
Is it important to get that diagnosis as early as possible?
Dr. Garvin: It’s always important to get the most correct diagnosis as early as possible for several reasons. The first is to make available all the treatments that you can to treat the individuals symptoms. If you have the correct diagnosis then the appropriate medicines can be prescribed. The second part of that is if you have the correct diagnosis, then you’ll avoid getting inappropriate medications. Some of which can have very serious consequences. For example, behavioral symptoms for Lewy Body Dementia are quite common. However, some of the classic medicines that we use to treat behaviors can have near fatal responses in patients with Lewy Body Dementia. It’s very important to establish the correct diagnosis.
What would a person notice from their loved one as far as behavioral symptoms? What might someone start seeing or what might the patient start feeling?
Dr. Galvin: The diagnosis of Lewy Body Dementia revolves around a collection of symptoms. There’s an international consortium where we’ve gone through several revisions of the criteria. This is the current criteria. First there has to be a dementia. That is a progressive change in cognitive abilities that interferes with your ability to function on an everyday basis. The features of that tend to be less about memory problems, and more revolving around attention, executive abilities like solving problems, and visual perceptual problems. It’s a little different than the type of symptoms that you see in Alzheimer’s Disease. The second are a group of core features that is not all of them need to be present, but they’re typically present in one way, shape or form in most patients. The first is signs of Parkinsonism: slow movement, balance problems and rigidity or stiffness. The second are prominent visual hallucinations. That is seeing things that aren’t there. The hallucinations typically are very well formed of either little people or furry animals. The third symptom is what we call cognitive fluctuation. This is a spontaneous change in the level of alertness, orientation, and concentration. People can be bright eyed and cheery talking to you and then they’ll kind of phase out a blank look, staring spells, breaking from a logical train of thought to an illogical or incoherent train of thought, and excessive sleepiness. The last core clinical feature is something called REM sleep behavior disorder. REM is your rapid eye movement or your dream sleep. These are people who act out their dreams. Typically during the dreams only thing that can move are your eyes so they’re moving around rapidly. During REM sleep disorder your muscles become active and you act out the dream. You vocalize, shout, talk, thrash, yell, kick, and punch. You can have very complex movements and do whatever the dream is doing at that time. Most of the dreams tend to be of a violent nature so you’re fending off attacks. Now the patient is sleeping and they don’t realize this but the bed partner realizes because they’re the ones that are getting hit, punched and kicked. That’s typically a complaint. Besides that, there are a number of other clinical features that aren’t sufficient to make the diagnosis but are very prominent in the disease. One of them in particularly is symptoms that affect the autonomic nervous system. Your autonomic nervous system does all of the things that you don’t have to think about, right? Your heartbeat, your blood pressure, your digestion, moving your bowels, passing your urine, those are all the things you don’t have to consciously think about. Lewy bodies are not just found in the brain but they’re found in any nervous system tissue in the body. If you have Lewy bodies in the wall of your colon, this can lead to chronic constipation; this is a very significant problem. If it’s in the wall of the bladder they could have urinary frequency and urgency as well as trouble emptying their bladder. If they’re in the nasal passages, they have a loss of smell. They have lots of other symptoms none of them are specific enough but if you ask the patients nearly all the families will report that these symptoms began maybe fifteen or twenty years before the memory symptoms began.
Is there a genetic component to this? Are people are starting with symptoms of this possibly twenty years before?
Dr. Galvin: It’s a degenerative disease, we’re not born with Lewy bodies, instead they eventually develop in some people. We know almost everything about Lewy bodies except why they occur in the first place. That’s true for a lot of brain diseases, once it happens we can tell you a tremendous amount of information. However, why two people sitting in a chair and one gets disease and one doesn’t get disease, often we don’t know that answer. Lewy Body Dementia by and large is not genetic. There are a small percentage of cases that are, they’re associated with several gene mutations but most cases are what we call sporadic. They occur randomly in the population. Unlike Alzheimer’s disease, Lewy Body Dementia tends to be more prominent in men than in women, whereas Alzheimer’s disease is a little more prominent in women than in men.
Does it affect a specific age?
Dr. Galvin: All of the degenerative dementias including Alzheimer’s disease can really affect people at any age, but typically we think about them as being age-associated diseases. The older you are the higher the risk. In general people with Lewy Body Dementia will be about ten years younger than the people who have Alzheimer’s Disease. While the number of people who have Alzheimer’s disease increases dramatically after age 65, most patients are in their eighties. For Lewy Body Dementia most patients will be in their seventies, and then people beyond the ranges of that. You can see cases as soon as the late thirties or forties, but that’s rare. The Lewy Body patients will tend to be on average younger than the Alzheimer’s patients. They’ll tend to be men instead of women.
Until this point has there been a treatment for Lewy Body Disease or has it been the use of other medications for other dementias?
Dr. Galvin: At the present time there are no approved medications specifically indicated for Lewy Body Dementia. What we have done is we’ve used medications that are available for other diseases to treat the symptoms. We borrow medicines from the Alzheimer’s world to treat the memory symptoms. We borrow medicines from the Parkinson’s world to treat the movement symptoms. We borrow medicines from the psychiatry world to treat the behavioral symptoms. We use medicines and they can be effective, but they’re not specifically indicated so that’s called off-label use. 2016 actually was the first registered trial for a medication specifically for indication for Lewy Body Dementia.
Talk a little bit about the trial and what is going on here at FAU.
Dr. Galvin: The medicine works on a neurochemical in the brain called serotonin. Serotonin does a lot of things, but one of the things it can do is enhance the release of other chemicals responsible for memory and learning. The goal of this medicine which is called Intepridine, or RVT-101, is to block the serotonin receptor to increase the amount of Acetylcholine in the brain. To make it simple, Acetylcholine acts as sort of the primer to make a new memory, you need the Acetylcholine to make a new memory. In degenerative diseases there’s less Acetylcholine around. What Intepridine tries to do is increase the amount of Acetylcholine that’s around. The more that’s around the more likely you are to form a new memory. It’s a symptomatic treatment to try to enhance the system.
As of now the clinical trial is going on correct?
Dr. Galvin: The clinical trial is going on around the world, and there are sites throughout the United States. We’re one of the sites in Florida and we’ve been very successful in recruiting patients to participate in this study. There’s two parts to the study, there’s a double blind phase; that is one group gets the placebo and one group gets the active medicine and neither the patient nor the investigator knows what they’re getting. When they finish the double blind phase they can go on what’s called an open label extension, so that everybody gets the medicine and we know that they’re getting the medicine. We still don’t know what they originally were on though and so we can look at the longer term effects of the medication. We are now moving people out of the double blind phase in to the open label extension phase.
Are you seeing any differences or results in your patients?
Dr. Galvin: It’s always hard to tell for sure because we’re blind. We don’t know what they’re getting. One of the things we hope to see are a delay or a slowing of the cognitive symptoms. A secondary feature may be some improvement in their balance and their walking. There are people that we get some hint that maybe we’re seeing something, but again we don’t know for sure and the blind is still kept during the study so that we don’t introduce bias into the results. That’s important – once bias is introduced into a trial it’s very hard to interpret the results of the trial. While it sounds unfair in one way to have a person you know on a placebo versus a medicine, the only way to demonstrate the medicine actually works is to compare it to something and that’s the placebo.
This is not to be a clear cure for LBD; this is a treatment that once a person is diagnosed can slow the progression of it?
Dr. Galvin: These medicines that we’re testing are including all the medicines that are currently on the market that we borrow from other disorders, which are symptomatic treatments. They are meant to reduce the symptom burden of the disease. They do not address the underlying pathology of the disease. Curing a disease is very difficult, because before someone has a symptom there has to be a degenerative process that begins years before. By the time someone has a symptom there’s already a lot of damage done to the brain systems. Cures are difficult to figure out how to build, I think they’re possible but they’re more difficult. Symptomatic medicines are much easier to design because in fact you’re addressing a symptom.
Can you tell us about the patient? He’s very athletic, and a very healthy person.
Dr. Galvin: Michael presented to the research project was first diagnosed with Lewy Body Dementia. Michael was a very active person, was a nationally ranked pickleball player, avid biker, and avid exercise individual. In fact my striking impression of Michael and his lovely wife are every time they come to visit, they’re in their exercise garb and they have matching florescent green outfits. They’re both very physically active. One of the greatest impacts of the disease on Michael was the loss of his ability to keep up with that physical activity. This was a lot of the way I think he identified himself, and because of his balance problems and his risk of falling doing all those activities became very, very difficult. In addition to being in the clinical trial we also started to provide medical care for him. One of the first things we did was to develop a plan to keep up his quality of life by altering his regiment. He liked to wear flip flops and we moved him out of flip flops to athletic shoes so he had a better base. He loves to bike so we got him out of a two wheeler into a recumbent bike that has three wheels. So he can go anywhere he wants to bike to, but he has less of a possibility of tipping over, it’s actually quite hard to tip over a recumbent bike. My understanding and you can ask him about that, is he is the envy of everybody in his community with this bike, everybody wants to know where he got his bike from. We moved him into an athletic wheelchair so while he can walk, he can use the wheelchair to play sports. Now he’s beginning to play pickleball and other athletic activities again from the wheelchair and getting a good workout. I think that’s an important part of what we do, it’s not making people live longer it’s making people live better. Focusing on the person as a whole and what’s important to them. That’s a major emphasis of what we do here.
Can depression be a part of it?
Dr. Galvin: Well depression can be a part of the issue, but not just depression but how you identify, how you see yourself is really important, that relates to your quality of life. If I gave you a medicine that made you score three points better on a mental status test, but didn’t do anything for you as a person that might not be something that you would perceive as a benefit. If I gave you a medicine that only improved your memory testing at one point, but now you’re able to do your everyday activities that might be perceived as a much greater benefit. I think it’s a balance, it’s looking at test scores but it’s also looking at the person as a whole.
Do you feel that the results of this study will have a huge impact for people who might be facing this disease?
Dr. Galvin: I think regardless of what the result of the trial is doing the trial is going to have a huge impact on people with the disease because previously there have not been any studies for Dementia with Lewy bodies. You have to be the trail blazer and break down the door to allow things like this to happen. With that said, we’re very hopeful that the medicine will in fact have a significant effect. A cousin medication of what we’re doing in one trial had some preliminary results which showed some promise in improving movement. I think we’re on the right path; the hope of course is that we break through that glass ceiling and have a treatment that’s approved. I think every step is a very positive step forward to addressing this important problem.
I know you’re still in the middle of this trial, but any idea of when it might be available?
Dr. Galvin: It’s only a six month trial in terms of its active phase, the double blind phase. That depends on when the last person is recruited. The study is about half way; a little bit more than half way recruited so the trial would close six months after the last patient comes in. Six months later we have the last patient out. At that point, there’s a data lock and data can begin to be analyzed in order to determine the results. Based on what we’re seeing so far we hope to have recruitment done somewhere between the end of the first quarter of this year or the beginning of the second quarter. Six months later the last patient would exit the trial which would put us probably in the third or fourth quarter of 2017. That’s probably the earliest we could get a peek at the data to get a sense of what we’re seeing. I think you know that’s probably an optimistic but possibly realistic timeline. If recruitment is slower, then obviously it’s going to take longer to get the results. People are working very hard to bring people into the study and we’ve been successful, and many other sites have been successful at getting people involved. I think the combined effort of all the sites will obviously give us the data we’ll need to prove whether the medicine works or not.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
(561) 297-0164
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here.
