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

Thursday, May 27, 2021
2:00 pm CST

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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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.

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