Webinar: Epilepsy and Neurodegenerative Disorders: The Relationship Between Stroke and Seizures

Epilepsy is commonly associated with many neurodegenerative disorders – which are characterized by motor neuron loss. While stroke is not considered a neurodegenerative disorder, it is commonly associated with many of these disorders (dementia, Parkinson’s, etc.) that primarily occur in older adults. There has been a great deal of focus among the research community on the relationship between stroke and seizures, as a 2013 study found that 7% of patients who suffered a stroke went on to develop epilepsy.1 Post-stroke seizures are often associated with significantly increased mortality and severe disability in patients with a history of stroke. Unraveling these associations is a high clinical and research priority. Trials of interventions to prevent seizures may be warranted.2

In this webinar, attendees will learn:

  1. the epidemiology of post-stroke epilepsy.
  2. the complications of post-stroke epilepsy.
  3. the international efforts to promote research on this topic, as well as the challenges associated with them.

1Conrad J, Pawlowski M, Dogan M, et al. Seizures after cerebrovascular events: Risk factors and clinical features. Seizure. 2013;22(4):275-82. doi:1016/j.seizure.2013.01.014

2https://pubmed.ncbi.nlm.nih.gov/37721736/

This will be the first in a series of CURE Epilepsy webinars that will discuss the relationship between epilepsy and neurodegenerative disorders, released intermittently over the next year. Please see www.CUREepilepsy.org/webinars for more information on all of our webinars.

 


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About the Speaker:

Dr. Nishant K. Mishra is the convener of the International Post Stroke Epilepsy Research Consortium (IPSERC), which he founded with Dr. Patrick Kwan, a Professor of Epileptology at Monash University, in 2021.  He has been an active stroke researcher for the last two decades and currently focuses on understanding the mechanisms of post-stroke epilepsy. Advances in acute stroke management have led to improved survival after stroke, and therefore, more people are expected to have post-stroke epilepsy. It has become critical to speak to stroke patients to create awareness about the complications of stroke and understand their needs, e.g., how this condition affects their care and their quality of life.  For example, these patients struggle to get back to driving because of physical deficits, including challenges from neglect and apraxia and the risk of unexpected future complications like seizures. Some stroke patients suffer from early seizures, e.g., acute symptomatic seizures and status epilepticus, and are, therefore, on antiseizure medications. Despite antiseizure medicines, many patients suffer from seizure recurrence. Dr Mishra will share his independent viewpoints about this medical problem in this webinar.

He is currently employed as the Stroke Director at the West Haven VA Medical Center and a stroke neurologist at the Yale New Haven Hospital. As a full-time faculty at Yale University, he conducts clinical research to improve the care of stroke patients.

 

Q&A with Dr. Nishant K. Mishra

For people who have had a stroke and they’re concerned about what the consequences of that could be, how would you recommend having a discussion with the doctor? Because often you’re seen by a stroke doctor and then you move on to somebody else. So who’s the right person to bring these concerns to, and how does somebody who’s had a stroke have this conversation? What are your recommendations?

I think this is a very important question and I think so commonly when patients develop stroke and they come to our clinics, we typically deal with the medications. We talk about aspirin, Plavix, or the need for anti-coagulation test to look for a presence of atrial fibrillation, more of these kind of questions. We don’t typically discuss mood, cognition, fatigue, post-stroke epilepsy, which I think are also important topics that we as stroke physicians should be tackling, discussing to offer a comprehensive care to our stroke population.

Same goes to, in terms of questions around driving, for instance. We want to know which patient population is at a higher risk of having a post-stroke epilepsy and are they able to or should we let them drive or not? So there are many questions that linger in the mind of patients and through the effort like this, thanks to your organization, we need to really promote this topic so that our clinic follow-ups from the stroke standpoint are really more comprehensive wherein we are tackling not only the medicine aspect but also cognitive poststroke epilepsy.

I think stroke doctors are the right doctors who should be tackling it early on. Obviously, we send patients for rehab and our MDs with physical medicine and rehabilitation training experience, another set of colleagues who should be able to guide this patient population. Epileptologist as well. I’m really delighted to see a lot of discussion on cardiovascular disease management in the epilepsy conferences these days. So I think even though our specialties are different, our mission is same, which is to promote outcomes in our patient population. So we should feel comfortable tackling these questions.

Would you consider the genesis of epilepsy as a type of TBI?

From the stroke standpoint, after a stroke, there are some animal data, some research from various colleagues that suggest that there is activation of the inflammatory pathways. There is a damage to blood brain barrier. There are certain molecules like TGF beta which seep into this blood-brain barrier, disrupted regions, accumulation of albumin.

There are some biological mechanisms which have been talked about and linked to the occurrence of post-stroke epileptogenesis. One would imagine that because inflammation is the cause and if we use anti-inflammatory agents, we should be able to prevent post-stroke epilepsy. It’s very simplistic, however, because as we know the inflammation is on the one hand it’s useful because it helps repair the bodies once it’s undergoing the effect of the injury.

On the other hand, if it persists long enough can be detrimental. And where exactly is the right balance? We don’t know. Unfortunately, we don’t have targeted therapies for this. There are some studies which… For instance, there is a study in which people have… There’s this one person investigator who has looked at the newer and anticoagulant dabigatran inhibiting some of these pathways and is associated with reducing the risk of epileptogenesis in the animal models.

Dabigatran is an anticoagulant. There is a possible way to remove the anticoagulant effect of these molecules and retain the potential antiepileptogenic, anti-inflammatory pathways. But the research of that kind needs to first go through the animals, needs to be validated. It has to go through phase one, phase two studies, and then eventually. There is also some talk on the topic that there are already some anti-inflammatory agents, which we are used to using and may potentially be repurposed.

But those medications are for really other inflammatory diseases to safely offer them to a patient population which is suffering from other cardiovascular risk factors. We really need to do a thorough thinking and test them in a safe way in clinical trials before anything like that would be available for patients. There is one colleague who is looking at the fact of Losartan, which is an antihypertensive agent. And based on some animal model studies, it may have some effect in saving the blood-brain barrier from getting worse or securing the blood-brain barrier.

We use Losartan for blood pressure management anyways, but it again hasn’t been tested in the clinical trials. Same would go with the statins, the medications like atorvastatin about which I showed you in one of the slides, that there is a systematic review and meta-analysis which suggested that it’s associated with reduced risk of post-stroke epilepsy that again needs to be tested in clinical trials.

We know that the statins have a pleiotropic effect, which means that in addition to reducing the levels of the cholesterol in the blood, it also keeps the blood vessels healthy and reduces the inflammation there. So in short, it seems like there is a need for more investigation from understanding the inflammatory pathways, which again requires more collaborative global effort.

Can you talk about the group that you have convened and what you hope to achieve in the next few years?

So the need for the consortium came from the realization that on the one hand I showed you in one slide that the risk of having post-stroke epilepsy is very high in the older population, age above 60. We also know that stroke is a global problem. A large number of patient population have stroke, but the estimates for post-stroke epilepsy is around 10%, eight to 10% depending on which study we look at. So no single center would be able to accumulate significantly large number of patient population to allow meaningful analysis of their data to reach conclusions.

So for instance, the select score, the study that I showed those colleagues, they accumulated collected data from multiple centers in Switzerland and few other countries in Europe. So our goal with this consortium is to bring in colleagues with range of different expertise in stroke epilepsy, animal model, data mining and first highlight the important questions, show that this question is important and also write collaborative grants so that we are able to, number one, detect the meaningful biomarkers, which can be used for clinical trial design and also discuss the design issues potentially also start running some clinical trials using some drugs which appear to have some signal of anti-epileptogenesis for instance, my colleague and co-convener, Patrick Kwan, who’s an epileptologist in Monash, Australia leading figure in the field.

He and his colleagues are doing an investigation looking at Perampanel. Perampanel is a medication for a seizure management. They’re doing a pilot study. And there is another colleague, senior colleague, Dr. Matthias Koepp. He’s testing one anti-seizure medication. But we need to really come together so that we are able to design trials, which really serve the purpose because we would not want our effort to go waste doing running trials, which are poorly designed. One more mission that I have, and I would like the support of everyone here is what is it about this condition that makes most sense to our patient population? Why is it so important? Right?

Dr. Mishra doing a research on a topic that is not meaningful to patient population, does no service to the field. So we are interested. We are creating writing surveys, which soon we will be spreading across in different countries, trying to understand what is it that’s meaningful in terms of patient-reported outcomes to the patient, their caregivers, family members. So, these are the kind of question which we need to tackle and create a framework so that we can have larger future studies which are more meaningful and really advance the field.

 


The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified healthcare professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified healthcare professionals who are familiar with the individual’s specific health situation.

a younger man hugs his elderly father from behind as they smile at the camera

Aging and Epilepsy: Consequences and Comorbidities to Consider in Older Individuals

Epilepsy is the third-most common neurological disorder in people age 65 and older after stroke and dementia, conditions which themselves increase seizure risk.1

This webinar discussed the relationship between epilepsy, dementia, and stroke, and discussed whether people with epilepsy have an increased chance of developing dementia as they age. Viewers also learned about strategies that people with epilepsy can implement to reduce their risk for these conditions.

  1. World Health Organization. “Epilepsy: A Public Health Imperative.” Date: 2019. Date accessed: May 3, 2021. https://www.who.int/mental_health/neurology/epilepsy/report_2019/en/ 


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Want to learn more about epilepsy and aging? Check out our Seizing Life episode, The Impact of Epilepsy and Seizures on Cognition and Memory, with Dr. Lam.


About the Speaker
Dr. Alice Lam is Assistant Professor of Neurology at Harvard Medical School and the Massachusetts General Hospital. As a physician, Dr. Lam takes care of patients in both the subspecialty Epilepsy Clinic as well as the Memory Disorders Unit. Her clinical and translational research program explores the interface between epilepsy, the neurodegenerative diseases, and cognition, using a combination of neurophysiology, neuroimaging, artificial intelligence approaches and cognitive outcomes.


Q&A with Dr. Alice Lam

Our population is aging. The number of Americans over age 65 is going to double in the next 30 to 40 years. And as we’re getting older and watching people around us get older I think it’s totally natural to wonder how are we going to live our best lives when we’re older adults? We all want to have a sense of independence, we want to have the ability to do things for ourselves, to make decisions for ourselves. We all want to preserve our memory, our ability to think clearly, to interact meaningfully with the world around us and to have ourselves represented.

How will having epilepsy affect your brain as you get older?

Dr. Alice Lam: Let’s start with a pop quiz. The first question is what age group has the highest proportion of people who are currently living with epilepsy? That’s regardless of when they’re actually diagnosed with epilepsy. Is it children, young to middle-aged adults, or older adults? I’ll give you the second question, which is, what age group has the highest chance of developing epilepsy, meaning being newly diagnosed with epilepsy?

The answer turns out for both questions is the same, it’s older adults.

People over age 65 are most likely to either have a diagnosis of epilepsy already, meaning they developed epilepsy as kids or as adults and have now grown old with epilepsy, or to develop epilepsy for the first time. And in the United States alone, over 100,000 older adults each year are newly diagnosed as having epilepsy.

Older adults are the fastest growing demographic in the U.S. as well. I told you earlier that the number of older adults is estimated to double in the next 30 to 40 years, so now I hope you can see why aging and epilepsy is such an important topic, this is a public health issue. It affects a lot of people currently and it’s going to affect a lot more people in the next few decades.

What are changes in our thinking and memory that happen normally as we age and how does that differ from dementia? Does having epilepsy increase my chances of developing dementia?

Dr. Alice Lam: Yes, having epilepsy does increase your risk of dementia, and it does increase your risk of stroke. But the good news is that you can substantially reduce your risk of both dementia and stroke with some very simple changes in your day-to-day life.

We lose brain cells, we lose connections between brain cells. Some brain cells shrink in size and the wiring between brain cells also shrinks. And related to these structural changes, our cognitive abilities also change.

We know that as people get older even if they’re healthy we start to have slower processing speed. Our working memory gets a little worse, our autobiographical memory, meaning our recollection of events that happened to us earlier in life, these details start to get a little bit fuzzier, and our ability to solve problems, come up with new ways of doing things also declines. But it’s important to note that these normal changes even though they exist they’re pretty subtle so many people might not even realize or might not be aware that these changes are happening. And these changes are generally not significant enough to interfere with a person’s ability to perform their daily activities.

How is normal brain aging? How’s that different from dementia?

Dr. Alice Lam: We know that there are some cognitive declines that happen in normal aging, but when people start to have a decline in their cognition that is more than we’d expect for normal aging, then we start to worry about whether or not they might have dementia. And so the precursor to dementia is called mild cognitive impairment. People with mild cognitive impairment have a decline in their thinking that’s significant often, so they notice it themselves or their friends or their families notice it. But despite this decline they’re actually still functioning pretty well. They can still work, they can drive, they can take care of their finances, they can cook meals, they can do all the things that they would normally do in their daily life.

When someone’s cognitive impairments become severe enough that they start to have problems with their activities of daily living, then we say that that person’s developed dementia. This might mean that they’re no longer able to figure out how to pay their bills or they’re no longer able to work a job that they’ve worked for the past 10 or 20 years, or they’re no longer able to figure out how to cook meals. So there’s different stages of dementia depending on how cognitively and how often functionally impaired someone is.

How do we explain this mismatch that you we can have someone with severe brain pathology whose mind is still able to function at a very high level?

Dr. Alice Lam: Well, one of the ways to explain this is a concept that’s called cognitive reserve. You can think of cognitive reserve as your brain’s ability to function well even the setting of having brain disease or having an injury to your brain. Cognitive reserve is how well your brain is able to compensate for disease or for injury. It’s your brain’s ability to find other ways of getting a job done if the usual way of getting things done suddenly becomes unavailable. I think about cognitive reserve in terms of brain networks, how different parts of the brain communicate and work together. And high cognitive reserve means that you’ve developed brain networks that are efficient and that are flexible.

Let’s say you live in this town and you want to go from your house to the pool, that’s pretty easy. There is a road that connects those things directly. All right. Think of brain networks as a system of roads in the brain that connects different parts of the brain that need to work together. What happens if there’s damage to a brain network, for example, from a stroke or even from a disease like Alzheimer’s disease? What happens if the damage affects this brain network that goes from your house to the pool and you can’t use it anymore? Now, how are you going to get from the house to the pool?

If you had developed other roads, other brain networks, even if this one road was blocked you might still be able to figure out how to get from your house to the pool. So you could take this path or you can take this path. These paths may not be as efficient, they might not work as well as the original road you are using but you’ve used these other networks to compensate for the fact that that main network is no longer working. That’s what cognitive reserve allows you to do.

I think that one of the best things about cognitive reserve is that it’s closely related to your life experiences and to your lifestyle. And that means that cognitive reserve is something that we can actually modify and improve over the course of our lives. We know that things like education and activities that are intellectually or socially stimulating, these things can greatly build cognitive reserve, and these factors actually it turns out can reduce your risk of dementia by 30 to 40%. While a lot of what I’ll say in this talk may sound like doom and gloom and no one wants to hear that they have an increased risk of dementia, what I want you to know now is that you can actually do something to reduce this risk, you can build cognitive reserve.

How does having more cognitive reserve actually allow you to reduce your risk of dementia?

Dr. Alice Lam: Let’s imagine someone who has early stages of Alzheimer’s disease. And Alzheimer’s disease, it’s a slowly progressive disease where your cognitive function gradually worsens over several years. Now, when this person’s cognitive function declines enough that it starts to interfere with this person’s daily activities, they’ve crossed the threshold and we can say that this person has developed dementia.

Now, what would this curve look like if this person had a severe head injury a few years back? Well, if they had a severe head injury there’s likely been damage to some of their brain networks and other brain networks are now having to compensate for that injury, so this person will be starting out with less cognitive reserve. And with less cognitive reserve but the same amount of Alzheimer’s disease pathology in the brain this person is going to be on a different trajectory shown on this red curve here. And you can see with less cognitive reserve this person will actually develop dementia at an earlier age compared to if they hadn’t had this brain injury.

Now, let’s take the opposite example. Okay, let’s take someone who has a healthy brain, a high amount of cognitive reserve. Someone who has high cognitive reserve, even with the same amount of Alzheimer’s disease pathology in the brain will actually develop dementia at a later age. And depending on how much later this age it’s possible that they might actually pass away from something completely different before they even ever develop memory problems or dementia. And so you can live your whole life without ever developing dementia because you’re able to kind of push it far enough down the line.

The bottom line that I want to make here is that brain injuries and low cognitive reserve, these things put people at increased risk of developing dementia earlier in life than they normally would. Whereas high cognitive reserve can actually delay the onset of dementia and in some people it might delay the onset of dementia to such an extent that for all practical purposes it’s prevented that person from getting dementia. That’s why cognitive reserve is really important.

How might this apply to people with epilepsy?

Dr. Alice Lam: The bad news is that people with epilepsy are two to three times more likely to develop dementia compared to people without epilepsy. Let’s say there’s a large amount of person to person variability in calculating this risk and there’s many factors that determine a given individual’s risk of developing dementia. And some of these things they might include things like when did you first develop epilepsy? What’s the cause of your epilepsy? How frequently do you seizures? How many and which seizure medications do you take? How long have you been taking seizure medications? And do you have depression or anxiety? Now, it can be tricky to try to figure out the individual contribution of each of these things because many of these factors are pretty closely intertwined. If you have frequent seizures you’re probably going to be on more seizure medications, and if you developed epilepsy early in life you’re probably going to have been taking seizure medications for a longer period of time. So it’s a little complicated to tease apart.

I’ve been talking a lot about the risk of developing dementia in someone with epilepsy but what I want to point out here is that most memory problems in people with epilepsy aren’t actually related to dementia. I think that this is something that my patients ask me about a lot because I think most people are… Dementia is one of the most worrisome things for a lot of people because right now we don’t have cures for diseases like Alzheimer’s disease or vascular dementia. But as I said earlier there are a lot of things we can be doing to reduce our risk of developing dementia and the setting of these diseases.

What can we do to keep our brains as healthy as possible as we get older? What are the things that we can do to actually maintain our brain health?

Dr. Alice Lam: Up to one in three cases of dementia could be prevented with just simple changes in lifestyle. What I’m going to share with you are recommendations that are largely agreed upon by many major health organizations on how to maintain brain health. And this applies not just to people with epilepsy, actually these are recommendations that are made to adults, essentially people who will be growing older. And these recommendations though I think that they are informative for people with epilepsy again because as I talked about people with epilepsy have a lot of these risk factors as they’re accumulating through life.

First, there are things we can do to increase cognitive reserve, and the biggest one there is to keep your mind active. Think of this as exercise for your brain. This could be reading, doing crossword puzzles, playing card games, using the computer, photography, playing a musical instrument, things that keep your mind going. We know that cognitive activity in mid and late life is associated with a 30 to 40% reduced risk of dementia, so really important to keep your mind active throughout life.

Second one there, protect your brain from injuries. Now, particularly for people with epilepsy seizures can put you at risk for head injuries and this is not something that you have much control over, unfortunately, but that means that you need to be extra careful and protect your brain when you can. So simple things like wearing a helmet if you’re riding a bike or wearing your seatbelt in a car. And then getting enough sleep, these are all things that will boost your cognitive reserve.

And then the third set of things as you might guess from the theme of this talk is controlling vascular risk factors, so stay physically active. The recommendation from the U.S. Department of Health and Human Services is that adults get 150 minutes of moderate intensity aerobic activity each week. What’s moderate intensity aerobic activity? This is pretty much any activity that gets your heart rate up, it gets your heart beating faster. It could be something like brisk walking, dancing, gardening, biking, water aerobics, things like that, but it’s really important to stay physically active.

Work with your primary care doctor to make sure that things like high blood pressure, diabetes, and cholesterol are controlled. These will reduce your cardiovascular risk. Quit smoking. I know that many people think about smoking primarily in terms of risk for lung cancer, but smoking it turns out is horrible for your blood vessels and it’s pretty horrible for your brain as well, so if you can quit smoking that may be one of the best things that you can actually do for your brain.

Eat a heart-healthy diet. What I often recommend to my patients is diet that’s similar to a Mediterranean diet. That’s a diet that has a lot of fresh fruits and vegetables, lean meats like chicken and fish, and try to avoid red meats like beef. And then finally avoid excessive alcohol consumption. There are mixed studies and you’ll probably hear on the news, whether small amounts of moderate amounts of alcohol may be good or bad for your brain health, so that’s mixed. But I think pretty much everyone agrees that excessive alcohol use which is basically more than one drink a day for women or more than two drinks a day for men that you should avoid that if you want to maintain good brain health.

The take home points for today. The bad news, epilepsy is associated with a two to threefold increased risk for dementia and stroke. The good news, staying mentally and physically active and controlling vascular risk factors can substantially reduce your risk for developing epilepsy and stroke. I hope that encourages you to go out, be mentally and physically active, and to try to keep your brains healthy as you grow older.

It is well-documented that AED side effects are more pronounced in the elderly because metabolism is slower. How should this be communicated to neurologists? Are they aware, and how often and what age do you recommend that dosages be lowered because of this?

Dr. Alice Lam: That’s a great question. The answer to that is a little complicated, but you’re definitely right that as people get older our metabolism slows. Our liver slows down the metabolism, our kidneys slow down eliminating medications from the bloodstream. But that’s also highly variable from individual to individual and as you know people have different body weights and there’s a lot of different variability person to person. I think if you’re aware of that and you think that this may be something that affects you I think it’s important to talk to your doctor about that.

One thing that your doctor can check, they can look at the level of seizure medicine that’s actually in your blood and that will give for you… That basically tells you how your body is metabolizing the amount of medication your doctor is prescribing for you. And it might turn out that maybe your doctor was unaware or your level was actually a lot higher than they thought it was and you might be able to reduce your dose of seizure. But that’s one objective way you can decide whether you’re on too much seizure medication as you get older.

Can Dilantin affect balance over time and do you have any comments on this or suggestions about what to do about it?

Dr. Alice Lam: Dilantin can definitely affect your balance and it can do that in a few different ways. One, if you’re on too high a dose of Dilantin you can actually have this Dilantin toxicity where you’re off balance and you’re wildly… Some people describe it as this feeling of being drunk without having had anything to drink. And so if your dose is too high you might notice that, and if that were the case you’ll probably notice it usually about the hour or two after you take your medicine. That’s one way it can affect dizziness.

Long-term it can also affect a dizziness in a number of different ways. Sometimes people can develop what we call a neuropathy that’s associated with long-term Dilantin use. That means that the nerves that go from your spinal cord down to your feet and help your brain know where your feet are and what they’re feeling on the ground below, those nerves can get damaged and you might not be able to feel your feet as well. And we also know that Dilantin over time can affect the cerebellum. That’s a structure in your brain that controls balance and coordination, things like that. So, yeah, I think that there is a fair amount of evidence that Dilantin can affect your balance but again it can do that in different ways.

Is there anything that can be done about that?

Dr. Alice Lam: Well, if you’re on too high a dose of Dilantin then obviously reducing the dose or trying to adjust how you take those doses or maybe even changing the medicine if it’s not the right medicine for you would be one way to do it. Obviously Dilantin is an older seizure medicine and I tend to avoid using it in older adults for a number of reasons. It tends to be older adults who are on it because if they were diagnosed with epilepsy years ago that’s what was available years ago and a lot of people are very comfortable staying on that medicine if it was working for their seizures, and so that’s often the case of patients who come to see me who are on Dilantin already.

There’s a lot of newer seizure medications that may not have those kinds of adverse effects, for one. Dilantin also, the way it’s metabolized is a little interesting and there can be interactions with a lot of other medications, not even just seizure medications but other common medications that you might take for other conditions. In an older adult if you’re running into these problems you might think about switching off of Dilantin for that reason, the medication interactions and these long-term effects that we know can happen with it.

If a person is over 80 and has had no seizure activity in 15 years, do you think medication dosages could be lowered?

Dr. Alice Lam: It’s something to think about, again, this is something that’s very individual and I can’t answer that without knowing more details of what happens to you when you’re having a seizure or what risk for injury might you incur if you did have a breakthrough seizure because you lowered your dose. But these are tricky questions. Even if I did know more about this person it’s not something that I could answer concretely, it’s something that really depends on the risk benefit ratio for each person and how willing they are to take a risk like that. I think you have to think about what would happen if you had a breakthrough seizure versus how bad it is to be on the level of medicine that you’re on right now. Are you having a lot of side effects from it or not? You just feel you want to be on a lower dose. The good thing is to discuss with your neurologist.

So a rupture of an arterial venous malformation maybe has led to development of tonic-clonic seizures and many cognitive issues, including problems with memory. Is there a greater risk of this person acquiring dementia as they age?

Dr. Alice Lam: Yes. So having this brain injury and having these cognitive issues that result you’re now at a lower cognitive reserve than you would have been before this AVM ruptured. And so I would say that, yeah, if you were to develop the kind of changes in your brain from Alzheimer’s disease you might be more susceptible to having dementia earlier from that than you would have had you not had this brain injury. But it doesn’t mean that you shouldn’t still try to reduce your risk for that.

At what point in time do you start having the discussion about driving or not driving?

Dr. Alice Lam: I think that sometimes people have awareness or insights to know when they feel it’s not safe for them to be driving. But it’s a really hard thing to actually make this assessment in my clinic, in my office, because I’m seeing somebody, I’m talking with them but I have no idea when they get behind the wheel how they would react to things. I don’t know, what would they do? Would they be able to stop in time if a kid ran out in front of the car to run after a ball or something like that? What would they do if a car swerved into their lane all of a sudden, how would you react to that? These kinds of things are really hard to gauge in a clinic.

One thing I’ll often do is sometimes I think it becomes pretty clear that someone shouldn’t be driving. They’re either getting into accidents or they’re getting lost while they’re driving, things like that. And those cases are a little bit more straightforward and often families will take away their loved one’s keys before even asking me about it. But when it gets a little grayer, when things aren’t quite working as well as you want to in your brain, but a lot of you’ve been driving your whole life, it’s an automatic thing almost, you don’t have to think about it so much.

What I’ll often do is I’ll recommend that people undergo a formal driving assessment. And so there are different centers that do this. There’s occupational therapists who are trained in assessing people’s safety in driving, and often this kind of driving assessment it may involve pen and paper tests first and if you do fine on that then you would do a behind the wheel on the road test where someone will be with you and assessing how you’re able to react to different things that happen. And so I often lean fairly heavily on these kinds of assessments to make a good assessment of that. It’s again, as I said, it’s really hard to know from just talking to someone in my office how they would actually do on the road.

Are some epilepsy medications worse for dementia?

Dr. Alice Lam: One way to ask it would be, are some epilepsy medications worse for cognition, not necessarily dementia? But I guess if they’re worse for cognition then they’re not going to help if you have dementia either. So if I ask my question, are some medicines worse for cognition? There are some medicines that we know have a worst cognitive profile compared to others.

Now, again my patients can respond very differently to seizure medicines. Again, there’s a lot of inter-individual variation, but generally there are some medicines that are thought to be relatively neutral or relatively… That they don’t really affect cognition too much. And those medicines that people often use in that case are levetiracetam or Keppra and lamotrigine or Lamictal. Those are thought to have relatively benign cognitive effects.

Tut then there are medicines that we know can definitely worsen cognition. These tend to be some of the older ones, so phenobarbital has been shown to have poor effects on cognition. Dilantin even can do that as well and carbamazepine. Some of these older medicines may have more of those more pronounced effects. But, yeah, I think, again, as in that slide where I looked at what kinds of things can affect memory in someone with epilepsy, choice of seizure medication can definitely do that. Topiramate, that’s another one that tends to affect cognition pretty badly.

How about zonisamide?

Dr. Alice Lam: It can. Again, it really varies from individual to individual. Zonisamide wouldn’t be on my top list for someone who’s having cognitive problems already, it would a bit further down the list. But I would say it’s not entirely neutral but it’s not as bad necessarily as some other ones. But everyone is… Again, I can have one patient who’s on a whopping dose of a medication, has no idea it’s in their system. And have another patient who’s on the same medication on a really tiny dose and is falling over because the side effects are so bad. So it’s really hard to predict that unless you actually just try it and see how you feel on it.

If somebody is feeling a cognitive impact and it’s possibly because of their medication, are those changes reversible if patients switch medications?

Dr. Alice Lam: Some of them can be, yeah. Again, if it tends to be a, “I just started this medicine a couple of months ago and I and my family are all noticing that I’m a lot slower on forgetting conversations.” Then yeah, in general come off that medicine. I would expect those side effects to get better as you’re off the medicine. But some of these older medicines like phenobarbital, Dilantin, if you’ve been on them for years and years and now you’re coming off them it may not be as great a benefit because there are some long-term changes from those medicines. So you might not notice as great a benefit but it might still be worth trying to come off them to see if you do get a benefit.

Can testing neuropsych evals tease out declines in cognition based on AED side-effects versus declines resulting from regular aging? Can testing determine the source of the cognitive decline?

Dr. Alice Lam: Yeah, that’s a great question. I use neuropsychological testing actually pretty frequently in my patients with epilepsy and memory problems. I think that there’s a number of things that can be helpful with it and often I do use it for the purposes that you’re talking about to try to tease apart what is actually causing this person’s cognitive impairments. Because one thing that neuropsych testing allows you to do is it really… I mean, if any of you have ever done neuropsych testing it’s a several hour-long cognitive test. You never knew that there are many tests for your learning and for your memory and things like that. So it’s very detailed and it can get in very good detail what parts of your thinking are working well and what parts of your thinking aren’t working well?

A lot of patients will say, “My memory is bad.” But actually it’s not their memory that’s bad, it may actually be their executive function, their ability to plan and organize things that’s more affected than their memory. And so neuropsych testing allows you to tease apart some of those things. And depending on what cognitive domain, whether it’s memory, executive function, language, any of those things, depending on which domains are affected, that can often help us hone in on what might be causing those changes.

And so sometimes that can help me distinguish between whether it’s someone’s longstanding epilepsy that’s causing their cognitive troubles or whether it might be something new or different, maybe they’ve developed dementia or maybe they’ve developed depression late in life. Trying to tease apart some of those factors, neuropsych testing can be helpful for that, yeah.

Is the ketogenic diet a heart-healthy diet?

Dr. Alice Lam: Oh, that’s a tough one, actually. I actually I don’t know the answer to that. I think it’s tricky because obviously it’s a very fat-intensive diet and I should actually look that up, but I do not know the answer to that offhand. I mean, I know that people who are on the ketogenic diet get monitored frequently. They have their cholesterol levels checked, they have a lot of these metabolic things checked. But I don’t know what the data is in terms of long-term, if it actually predisposes you to having heart attacks because of the high-fat content or not.

Does chronic microvascular ischemic change get worse with time and does it make epilepsy worse?

Dr. Alice Lam: Okay, that’s a good question. For those who don’t know what is chronic microvascular ischemic change, the best way I can describe it is let’s say you have an MRI that’s done. What it looks like on an MRI are these little white spots actually, these little white spots that you don’t normally see but you do tend to see them more as people get older. And what we think of these little white spots is that it’s reflecting damage to really small blood vessels in the brain. It’s showing you that there’s some disease of the small blood vessels, they’re affected somehow. And sometimes that can be due to the kinds of vascular risk factors that we’ve been talking about, high blood pressure can definitely do that. People who smoke definitely you’ll see a lot more of these microvascular changes in the brain.

Can that worsen… I think that was the question, can it worsen epilepsy? What I’ll say is, there have been studies that been done recently looking at what are the risk factors for people who develop late-onset epilepsy. And it turns out that people who have these chronic microvascular ischemic changes, again think of them almost silent changes. Most people don’t know that they’re there, it’s something that you see on MRI, on brain imaging when you do the imaging but they’re silent. Think of it as silent cerebrovascular disease. It tells you that your blood vessels are not as healthy as we’d like them to be.

But anyhow, if you have those kinds of changes in mid-life in your 40s and 50s, that is actually a risk factor for developing late-onset epilepsy. Whether if you already have epilepsy that kind of change will worsen your epilepsy. I’m not sure if we know that or not, but again, in terms of this vascular risk I’ve been talking about, think about this chronic microvascular change as another sign that maybe things aren’t as healthy as you want them to be.

Are there different outcomes on epilepsy in other areas of the brain, for example, parietal lobe? Has this been studied or has it just been focused on TLE?

Dr. Alice Lam: A lot of the studies on cognition and epilepsy have been done in people with temporal lobe epilepsy. It’s the most common focal epilepsy so there’s a lot more people that have it compared to things like parietal or occipital or frontal lobe epilepsy, that’s probably one of the reasons. But also we know that temporal lobe epilepsy affects the temporal lobes and we know that those are really important for memory as well. I think that historically that’s been the case and it’s hard to do… You need really big studies in order to make these kinds of observations or to get these kinds of insights you need a lot of patients over time too.

 

The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.

An elderly woman speaks with her doctor, who is explaining the prescription.

Epilepsy’s Impact on Memory and Cognition Over Time

Cognitive deficits and memory problems are common among adults with chronic epilepsy. This webinar discusses the course of cognitive and memory aging in people with chronic epilepsy. The presentation addresses factors which contribute to healthy cognitive and brain aging, as well as what patients can do to help prevent cognitive decline.

This webinar is presented by Dr. Bruce Hermann, PhD, Director of the Charles Matthew Neuropsychology Section at the University of Wisconsin School of Medicine and Public Health. Dr. Hermann is an expert in brain and cognitive aging in people with chronic epilepsy. His research focuses on the impact of epilepsy on brain structure, cognition, and psychiatric status.

Dr. Hermann’s presentation is followed by an interactive Q&A session, where he answers questions such as:

  • Can any measures be taken to prevent or combat the cognitive decline that accompanies getting older with epilepsy?
  • Does research suggest specific therapies to help prevent memory loss associated with epilepsy?
  • Are certain individuals with epilepsy more likely to experience cognitive decline as they age than others?

For the full transcript, click the link below.


Download Full Transcript

Audience Q&A with Dr. Bruce Hermann

How did researchers differentiate between the issues caused by antiepileptic drugs, and those that are caused by seizures?

Within the epileptic drugs, the best are the controlled clinical trials, right? And there’s quite a bit of research about that, right? So, patients come in, they’re randomized to drug A or drug B, they’re tested before they’re given those medications. And there are studies that have done this with healthy controls where they’ve taken no medications, and come into the study, and take some baseline testing, then are randomized to a drug treatment trial, and no treatment control trial.

And you can figure out the specific effects of particular drugs in that fashion. And they’ve also done this with patients with epilepsy, where they’re randomized to one arm or another, and you can look at the effects of an add-on medication or a new medication. There are now, there are some very large studies where they’ve taken people at diagnosis, and randomize them into a one arm or the other. And it could be such as the childhood absence study, which was a major national study in the US that even compare the effects of seizure control as well as cognition.

If there’s marginal or no differences in their ability to control the seizures, then really clearly the more preferred compound would be the one that has fewer cognitive complications. So, quite a big literature that addresses that through the years, and it’s been worked out pretty carefully, and I can send CURE some references for that that might be useful to everyone.

Is there research done when drugs come into the market on which medications, like Keppra that may have more of an impact on memory and cognition?

Yes. I mean, nowadays it’s worked out pretty carefully. So, we have a good sense of the cognitive complications with some of these medications. It becomes clearer over time for sure, but cognition is now integrated in many of these drug development clinical trials and so on. Again, don’t forget because what happens in my career, talk about cognition or talk about behavioral issues. Generally, the first question has to do with medications, and there’s no question that it can have an effect. But these problems are present right at the get go even before any medications are given.

Can the medications exacerbate the cognitive difficulty? Sure, they can, but they are countering the effects of the seizures themselves, which have their own adverse effects. So, this research looking at new onset drug naive patients is just incredibly important. And again, there are subsets, some individuals at onset have no difficulties, and have a very uncomplicated course, whereas others from a cognitive perspective have difficulties early on, and were struggling with some issues even before the diagnosis of epilepsy, which no one fully understands, but everybody has observed that.

Is there an advantage to adults actually having genetic testing done to determine their type of epilepsy, and could that have an impact on knowing the cognitive issues, and the memory issues that may arise?

No. I mean, I think in the cognitive aging world, and especially in the Alzheimer’s disease world, there are a couple of genes. I mean, it’s a complicated business. I work with a preclinical AAD group here, and there’s a lot of interest in genetics, and the primary gene has been the ApoE4 gene. I mean, there are genes for early onset dementia, but that’s not what people are worried about. They’re worried more about must having a family.

They’re worried more about the course over the decades, and as they get older. And there are a couple of genes, but it’s very poly genetic as they say, and you can have the gene, and not have Alzheimer’s disease. You can not have the gene and have Alzheimer’s disease. So, it’s probably what’s probably most important in midlife is probably to get after all the treatable factors, and my general opinion, and the research on that, we have folks here doing exercise research.

And in at-risk patients for Alzheimer’s disease, and the exercise has positive effects on brain structure. It has positive effects on laying down of the plaques. It has positive effects on cognition going forward. So, I’ve seen a diet study using the mind diet where white matter volumes increase over time. So, I think if you look at the websites for the various organizations I mentioned, I think that’s very important to take a look at. And it’s extremely important area of research for epilepsy. It’s just critical going forward.

Is there any research being done that shows that epilepsy patients are more or less likely to develop Alzheimer’s?

This is a very hot topic right now, and there’s a lot of interest in this, if we address it from the standpoint of comorbidity studies, is there a higher incidence between epilepsy seizures, and Alzheimer’s disease? There is a higher incidence, but that’s driven in part by people who have Alzheimer’s disease, and then develop seizures as part of that disease. The really complicated question is, and not that that’s not complicated, but the question that people with chronic epilepsy have is what’s my cognitive course?

We just don’t know too much about it because our literature cuts off about age 50. We need some large population-based studies that follow people into their older years. And that, we just don’t have. We need that, and that would include imaging, and cognition, and life health history. I think that’s why the Finland data are so important. They’ve collected all sorts of health activity, personal information on these patients at midlife. And one question would be is there anything in midlife that predicts the amyloid deposition in people in their 50s?

If something can be found there, then that would have huge implications in terms of what to do, and have some… just certainly generate testable hypotheses anyway in terms of are there things we can do to reduce that risk. And, that question is, I mean, what’s the risk of Alzheimer’s disease? It’s everywhere, you pick up the paper, listen to the news, and it drives a lot of interest in cognition.

Does epilepsy actually affect long-term memory or short-term memory, more than the other?

Yeah. I think the one thing we didn’t talk about is if you think about it, the seizures, I mean I’ve always been impressed for example, by moms who will say, “We studied for the test last night, yesterday afternoon, and Johnny knew everything, and you got cold, and you’re forwards, backwards, and had it all down, and had a seizure the night, or a seizure in the evening. And then the next morning, just didn’t recall any of the information.

They weren’t postictal, but it’s erased what they had learned. And in epilepsy, the seizures, I mean memory is a process. Consolidation takes place over time, over a long time period. And if something disrupts that process, then that won’t be remembered. And episodic seizures, and probably even the spikes, if people have some clinical seizures, and they’re not aware of, these things are taking place, and are affecting the laying down of new memories.

So, it could be that if a patient and spouse say, “Well, don’t you remember that trip we took four years ago?” They may not recall that because the consolidation process had been affected by seizures, spikes, or clinical seizures. And the subclinical seizures are really a problem because you’re not sure when those things occur. You see them in the monitoring units all the time. So, long-term memory can be affected, and it is an object of study at present.