Sleep and Neurodegenerative Diseases
Roneil Malkani, MD discusses Sleep and Neurodegenerative Diseases. She shares her recently published findings in the Neurobiology of Stress regarding the relationship between sleep and circadian rhythm disruption and neurodegenerative disease.
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Learn more about Roneil Malkani, MD
Roneil Malkani, MD
Roneil Malkani, MD focus of work includes Sleep and circadian disorders in neurodegenerative diseases, REM behavior disorder, parasomnias, Parkinson's disease, sleep disturbances in Parkinson's disease and Alzheimer's disease, restless legs syndrome, circadian rhythm disorders, sleep apnea, hypersomnia.Learn more about Roneil Malkani, MD
Transcription:
Sleep and Neurodegenerative Diseases
Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and today we’re discussing sleep and neurodegenerative diseases. Joining me is Dr. Roneil Malkani. He's an assistant professor of neurology at Northwestern Medicine. Dr. Malkani, it’s a pleasure to have you join us. Tell us a little bit about your role at Northwestern Medicine.
Roneil Malkani, MD (Guest): I'm a neurologist and a sleep specialist and also a movement disorder specialist at Northwestern Medicine. My primary place here at Northwestern Medicine is in the department of neurology and sleep medicine. I direct a specialized sleep clinic and sleep and circadian rhythms in patients with neurodegenerative disease such as Parkinson’s disease, Alzheimer’s disease, and dementia with Lewy bodies.
Host: Well thank you for telling us about that. You recently published findings in the European Journal of Neuroscience regarding circadian rhythms disruption’s role in neurodegenerative disease. Tell us about the background of your work and share your findings with us if you would.
Dr. Malkani: So thank you about bringing up that paper. So in that particular paper, my colleagues and I reviewed the role in circadian rhythm function in health and disease. In particular we highlighted the relationship between circadian rhythms in their role and when they go wrong in people with Parkinson’s disease and Alzheimer’s disease. So telling you a little bit about what are circadian rhythms. Circadian rhythms exist throughout the body. There are rhythms in every organ system. There are rhythms to your melatonin levels, to various hormones, in your temperature, in metabolism, and also in sleep and wake. In fact, sleep and wake is probably the one that everyone thinks about the most because there's a rhythm to when you go to bed and when you wake up. These are only a handful of the rhythms that exist in the body. These rhythms are all coordinated and synchronized in the brain so they're all usually aligned. There are many lines of evidence that have shown that circadian rhythms can be altered in people with Parkinson’s disease and Alzheimer’s disease. These changes correlate with the sleep disruption and the daytime function because when the rhythms are not working appropriately, or they're misaligned then the function can be not as good. So understanding the relationships to the circadian rhythms and sleep in these diseases is critical to understand the diseases and to help find new treatments so we can improve the function of the patients and their quality of life. We also need this to improve the quality of life of the caregivers because especially when there are sleep problems, this impacts not just the patients but the caregivers as well.
More interestingly, there's been recent evidence implicating that circadian rhythm problems and sleep problems can occur even before the first symptoms of Parkinson’s disease and Alzheimer’s disease. And that these problems may promote the neurodegenerative process and increase the risk of developing these diseases. This is why it’s critical that if we can identify circadian rhythm and sleep disruption early and address that, perhaps we can even alter the course of these diseases.
Host: Wow, that’s fascinating. It makes such perfect sense. So as you're telling us how circadian disruption promotes the development or can accelerate the progression of these neurodegenerative diseases you're talking about, what sleep disorders are you seeing that are most common among these individuals with these types of disorders and why are we seeing those?
Dr. Malkani: There are many ways that sleep, and circadian disruption can promote the neurodegenerative process. The most obvious way is through sleep and wake. So circadian rhythms and sleep and wake cycles are intricately linked. You cannot separate them. If you alter the circadian rhythm, you also disrupt the sleep. It’s also well known that sleep disruption can affect your cognitive functions. If you don’t sleep well, it’s harder to concentrate and focus the next day. Data over the past decade has shown that sleep disturbances also increase the risk of neurologic disease, in particular Alzheimer’s disease. So while awake your brain is active. It’s burning energy and you can get these metabolites that are not so good for accumulations. These are toxic metabolites. While asleep, your body clears them out. It’s cleared through a part of the brain called the glymphatic system. When you're asleep this system gets activated and your body clears out these metabolites. One of these metabolites is something called beta amyloid. It’s the hallmark protein that accumulates in Alzheimer’s disease. So if the sleep is disrupted, you can get greater accumulation of these metabolites and increased risk of normal formation and deposition of beta amyloid which could predispose you to Alzheimer’s disease.
Another way that sleep problems can promote neurodegeneration is through sleep apnea. Sleep apnea increases the risk of many diseases including high blood pressure, diabetes, heart disease, stroke. More recently it’s been shown to be a risk factor for both Alzheimer’s disease and vascular dementia. One of the hallmarks of sleep apnea is the sleep disruption because the problems with the breathing cause frequent arousals. These arousals could potentially effect the glymphatic system therefore you can't clear these metabolites. Then also get problems with your oxygen regulation and oxidative stress and inflammation, all which can promote neurodegeneration.
In terms of sleep disorders that we see in these people, there are many types. Some of them are also specific to certain types of diseases. The most common problem we see is insomnia. We also see daytime sleepiness. These issues can occur because of other problems such as sleep apnea or having to go to the bathroom frequently at night to urinate. Also it can occur because of disruption in the circadian rhythms or even in the sleep regulation process. An example here is in people with Parkinson’s disease, they often have fragmented sleep. Part of that is because they have problems with the sleep regulation and circadian rhythms. They can also get problems in their autonomic system which causes them to feel frequent urgency to urinate. This can also occur at night and they have to go to the bathroom frequently at night. These frequent bathroom trips can be very disruptive to their sleep. When they wake up to go to the bathroom, it can be difficult to go back to sleep which then further disrupts the sleep.
In people with Alzheimer’s disease, there's more prominent changes in the circadian rhythm. So they have reduced amplitudes in various rhythms. For example, they have less melatonin production which normally rises in the night and falls in the morning. They don’t have the same rise in their melatonin. They also tend to spend more time indoors. They are not as active. So their activity rhythms are also reduced. This reduction in their activity rhythms can also affect their sleep at night. So now they have more difficulty sleeping at night and more difficulty being active during the day.
There are other types of sleep disorders that we see in these patients. For example there’s a condition called REM sleep behavior disorder. This occurs in about half of people with Parkinson’s disease. So normally in REM sleep, which is the stage of sleep people typically have dreams, the body is normally is paralyzed except for eye movements and for breathing. This is advantageous because when you're dreaming about things, it wouldn’t be safe for your body to actually do them. So your body needs to stay fairly paralyzed and fairly still so that you don’t cause yourself any injuries. However, in people with REM behavior disorder, this normal paralysis stops working properly. As a result, the person can actually act out the dreams that they're having. This can lead to injuries to the bed partner and themselves. They can even jump out of the bed and injure themselves. The interesting thing about this disorder is that this can occur even before the first symptom of Parkinson’s disease or dementia. This tends to be linked more closely with Lewy body dementia rather than Alzheimer’s disease, but this can occur well before the first symptom of either Lewy body dementia or Parkinson’s disease by decades even. So these are patients in particular who are at risk for developing diseases. Understanding how this influences the risk of the disease and identifying ways that maybe we can even prevent the diseases is very important here.
Host: Well it certainly is. That was such a comprehensive answer. Dr. Malkani, tell us about the methods you're using to improve sleep and mitigate cognitive decline that’s associated with neurodegeneration. How does your approach to treatment help after this course?
Dr. Malkani: So unfortunately there's no treatments that have been shown to actually alter the course of the disease. We need to understand the changes that happen, when they happen, and we need to look at the treatments that we use to help improve sleep and see if this will improve the course or the risk of developing these diseases. There just isn’t the data available yet. There are many treatments that we use to improve the sleep function in these patients. For example, the treatments that we use depend on the exact problems any particular patient is having. For example, if sleep apnea is present then treatment for that can improve the daytime sleepiness, memory, insomnia. If they have problems with frequent nocturia at night then we can use medications to help with that. If they have this REM sleep behavior disorder, we can help control the dream enactments. If there is insomnia—which is the most common problem we see—we prefer to use a combination of mild sleeping medications. In particular we like to use cognitive behavioral therapy which is a group of non-mediation strategies aimed at improving sleep. This particular group of strategies works extremely well to treat insomnia in general. Our goal here is to improve both the sleep function and the quality of life for the patient and their caregiver.
Host: For other providers that are interested in this topic, what's unique about what you're doing at Northwestern Medicine?
Dr. Malkani: Our sleep and neurodegenerative clinic is a problem with particular expertise in this niche, which is not widely available. It’s not just myself. It’s our whole nursing staff. It’s our sleep laboratory where we have this expertise to evaluate and care for these patients. We have state of the art evaluation tools including sleep studies, actigraphy, melatonin sampling to evaluate these patients. We also have an active research program in sleep and aging in neurodegenerative disease so that we can help understand these diseases better and find new treatments.
Host: So as we wrap up, what conclusions would you like other providers to take away from this segment and your studies?
Dr. Malkani: I think the most important thing for providers to know is that sleep problems are very common in patients with neurodegenerative disease and that it is a big factor in their quality of life and the quality of life of their caregivers. These problems can be treated. These sleep problems can also predispose to neurodegenerative disease. So we need to identify sleep problems early on. Because these can be very complicated, and problems can relate to each other such as daytime sleepiness and insomnia can be related to each other. Then there's also neurological disease that needs to be addressed. It can take time and particular expertise’s to determine the best course of evaluation and treatment for these patients. We have a clinic just for this. Our specialized sleep and neurodegeneration clinic is available to help with these patients.
Host: What great information. Such a fascinating topic Dr. Malkani. It really does seem to fit together neurodegenerative diseases and sleep issues. Thank you for joining us and telling us about your studies and the clinic. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. To refer your patient or for more information on the latest advances in medicine please visit our website at nm.org or call us at 312-695-7950 to get connected with one of our providers.” Please also remember to subscribe, rate, and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.
Sleep and Neurodegenerative Diseases
Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and today we’re discussing sleep and neurodegenerative diseases. Joining me is Dr. Roneil Malkani. He's an assistant professor of neurology at Northwestern Medicine. Dr. Malkani, it’s a pleasure to have you join us. Tell us a little bit about your role at Northwestern Medicine.
Roneil Malkani, MD (Guest): I'm a neurologist and a sleep specialist and also a movement disorder specialist at Northwestern Medicine. My primary place here at Northwestern Medicine is in the department of neurology and sleep medicine. I direct a specialized sleep clinic and sleep and circadian rhythms in patients with neurodegenerative disease such as Parkinson’s disease, Alzheimer’s disease, and dementia with Lewy bodies.
Host: Well thank you for telling us about that. You recently published findings in the European Journal of Neuroscience regarding circadian rhythms disruption’s role in neurodegenerative disease. Tell us about the background of your work and share your findings with us if you would.
Dr. Malkani: So thank you about bringing up that paper. So in that particular paper, my colleagues and I reviewed the role in circadian rhythm function in health and disease. In particular we highlighted the relationship between circadian rhythms in their role and when they go wrong in people with Parkinson’s disease and Alzheimer’s disease. So telling you a little bit about what are circadian rhythms. Circadian rhythms exist throughout the body. There are rhythms in every organ system. There are rhythms to your melatonin levels, to various hormones, in your temperature, in metabolism, and also in sleep and wake. In fact, sleep and wake is probably the one that everyone thinks about the most because there's a rhythm to when you go to bed and when you wake up. These are only a handful of the rhythms that exist in the body. These rhythms are all coordinated and synchronized in the brain so they're all usually aligned. There are many lines of evidence that have shown that circadian rhythms can be altered in people with Parkinson’s disease and Alzheimer’s disease. These changes correlate with the sleep disruption and the daytime function because when the rhythms are not working appropriately, or they're misaligned then the function can be not as good. So understanding the relationships to the circadian rhythms and sleep in these diseases is critical to understand the diseases and to help find new treatments so we can improve the function of the patients and their quality of life. We also need this to improve the quality of life of the caregivers because especially when there are sleep problems, this impacts not just the patients but the caregivers as well.
More interestingly, there's been recent evidence implicating that circadian rhythm problems and sleep problems can occur even before the first symptoms of Parkinson’s disease and Alzheimer’s disease. And that these problems may promote the neurodegenerative process and increase the risk of developing these diseases. This is why it’s critical that if we can identify circadian rhythm and sleep disruption early and address that, perhaps we can even alter the course of these diseases.
Host: Wow, that’s fascinating. It makes such perfect sense. So as you're telling us how circadian disruption promotes the development or can accelerate the progression of these neurodegenerative diseases you're talking about, what sleep disorders are you seeing that are most common among these individuals with these types of disorders and why are we seeing those?
Dr. Malkani: There are many ways that sleep, and circadian disruption can promote the neurodegenerative process. The most obvious way is through sleep and wake. So circadian rhythms and sleep and wake cycles are intricately linked. You cannot separate them. If you alter the circadian rhythm, you also disrupt the sleep. It’s also well known that sleep disruption can affect your cognitive functions. If you don’t sleep well, it’s harder to concentrate and focus the next day. Data over the past decade has shown that sleep disturbances also increase the risk of neurologic disease, in particular Alzheimer’s disease. So while awake your brain is active. It’s burning energy and you can get these metabolites that are not so good for accumulations. These are toxic metabolites. While asleep, your body clears them out. It’s cleared through a part of the brain called the glymphatic system. When you're asleep this system gets activated and your body clears out these metabolites. One of these metabolites is something called beta amyloid. It’s the hallmark protein that accumulates in Alzheimer’s disease. So if the sleep is disrupted, you can get greater accumulation of these metabolites and increased risk of normal formation and deposition of beta amyloid which could predispose you to Alzheimer’s disease.
Another way that sleep problems can promote neurodegeneration is through sleep apnea. Sleep apnea increases the risk of many diseases including high blood pressure, diabetes, heart disease, stroke. More recently it’s been shown to be a risk factor for both Alzheimer’s disease and vascular dementia. One of the hallmarks of sleep apnea is the sleep disruption because the problems with the breathing cause frequent arousals. These arousals could potentially effect the glymphatic system therefore you can't clear these metabolites. Then also get problems with your oxygen regulation and oxidative stress and inflammation, all which can promote neurodegeneration.
In terms of sleep disorders that we see in these people, there are many types. Some of them are also specific to certain types of diseases. The most common problem we see is insomnia. We also see daytime sleepiness. These issues can occur because of other problems such as sleep apnea or having to go to the bathroom frequently at night to urinate. Also it can occur because of disruption in the circadian rhythms or even in the sleep regulation process. An example here is in people with Parkinson’s disease, they often have fragmented sleep. Part of that is because they have problems with the sleep regulation and circadian rhythms. They can also get problems in their autonomic system which causes them to feel frequent urgency to urinate. This can also occur at night and they have to go to the bathroom frequently at night. These frequent bathroom trips can be very disruptive to their sleep. When they wake up to go to the bathroom, it can be difficult to go back to sleep which then further disrupts the sleep.
In people with Alzheimer’s disease, there's more prominent changes in the circadian rhythm. So they have reduced amplitudes in various rhythms. For example, they have less melatonin production which normally rises in the night and falls in the morning. They don’t have the same rise in their melatonin. They also tend to spend more time indoors. They are not as active. So their activity rhythms are also reduced. This reduction in their activity rhythms can also affect their sleep at night. So now they have more difficulty sleeping at night and more difficulty being active during the day.
There are other types of sleep disorders that we see in these patients. For example there’s a condition called REM sleep behavior disorder. This occurs in about half of people with Parkinson’s disease. So normally in REM sleep, which is the stage of sleep people typically have dreams, the body is normally is paralyzed except for eye movements and for breathing. This is advantageous because when you're dreaming about things, it wouldn’t be safe for your body to actually do them. So your body needs to stay fairly paralyzed and fairly still so that you don’t cause yourself any injuries. However, in people with REM behavior disorder, this normal paralysis stops working properly. As a result, the person can actually act out the dreams that they're having. This can lead to injuries to the bed partner and themselves. They can even jump out of the bed and injure themselves. The interesting thing about this disorder is that this can occur even before the first symptom of Parkinson’s disease or dementia. This tends to be linked more closely with Lewy body dementia rather than Alzheimer’s disease, but this can occur well before the first symptom of either Lewy body dementia or Parkinson’s disease by decades even. So these are patients in particular who are at risk for developing diseases. Understanding how this influences the risk of the disease and identifying ways that maybe we can even prevent the diseases is very important here.
Host: Well it certainly is. That was such a comprehensive answer. Dr. Malkani, tell us about the methods you're using to improve sleep and mitigate cognitive decline that’s associated with neurodegeneration. How does your approach to treatment help after this course?
Dr. Malkani: So unfortunately there's no treatments that have been shown to actually alter the course of the disease. We need to understand the changes that happen, when they happen, and we need to look at the treatments that we use to help improve sleep and see if this will improve the course or the risk of developing these diseases. There just isn’t the data available yet. There are many treatments that we use to improve the sleep function in these patients. For example, the treatments that we use depend on the exact problems any particular patient is having. For example, if sleep apnea is present then treatment for that can improve the daytime sleepiness, memory, insomnia. If they have problems with frequent nocturia at night then we can use medications to help with that. If they have this REM sleep behavior disorder, we can help control the dream enactments. If there is insomnia—which is the most common problem we see—we prefer to use a combination of mild sleeping medications. In particular we like to use cognitive behavioral therapy which is a group of non-mediation strategies aimed at improving sleep. This particular group of strategies works extremely well to treat insomnia in general. Our goal here is to improve both the sleep function and the quality of life for the patient and their caregiver.
Host: For other providers that are interested in this topic, what's unique about what you're doing at Northwestern Medicine?
Dr. Malkani: Our sleep and neurodegenerative clinic is a problem with particular expertise in this niche, which is not widely available. It’s not just myself. It’s our whole nursing staff. It’s our sleep laboratory where we have this expertise to evaluate and care for these patients. We have state of the art evaluation tools including sleep studies, actigraphy, melatonin sampling to evaluate these patients. We also have an active research program in sleep and aging in neurodegenerative disease so that we can help understand these diseases better and find new treatments.
Host: So as we wrap up, what conclusions would you like other providers to take away from this segment and your studies?
Dr. Malkani: I think the most important thing for providers to know is that sleep problems are very common in patients with neurodegenerative disease and that it is a big factor in their quality of life and the quality of life of their caregivers. These problems can be treated. These sleep problems can also predispose to neurodegenerative disease. So we need to identify sleep problems early on. Because these can be very complicated, and problems can relate to each other such as daytime sleepiness and insomnia can be related to each other. Then there's also neurological disease that needs to be addressed. It can take time and particular expertise’s to determine the best course of evaluation and treatment for these patients. We have a clinic just for this. Our specialized sleep and neurodegeneration clinic is available to help with these patients.
Host: What great information. Such a fascinating topic Dr. Malkani. It really does seem to fit together neurodegenerative diseases and sleep issues. Thank you for joining us and telling us about your studies and the clinic. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. To refer your patient or for more information on the latest advances in medicine please visit our website at nm.org or call us at 312-695-7950 to get connected with one of our providers.” Please also remember to subscribe, rate, and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.