Epilepsy Impacting Memory, Attention, Perception - Cognition - Dr. Jake Pellinen, UCHealth, USA
Does epilepsy impact cognition? Could it be seizures, medications - or something that happened right at the beginning - even before seizures started? Hear all about it from epileptologist Dr. Jacob Pellinen who speaks of exciting answers - and questions - from the Human Epilepsy Project. Watch/listen/read here 👇!
Episode Highlights
Cognitive problems can preceed epilepsy onset
Cognitive problems aren’t necessarily caused by epilepsy
Cognitive and mental health problems must be addressed alonside seizures
About Jacob Pellinen
Jacob is a neurologist and epileptologist at UCHealth, the Medical Director for UCHealth Neurodiagnostics, and Associate Professor of Neurology at the University of Colorado Anschutz. He strives to provide the best possible care, individualising approaches to diagnosis and treatment, and taking all aspects of a person's health into consideration.
Full profile: Jacob Pellinen
Topics/terms mentioned
human epilepsy project
cognition
cogstate brief battery
Psychomotor function
Working memory
Attention
Visual learning
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Trailer
00:00 Jacob Pellinen
“There wasn't a big association between the number type of seizures people had prior to diagnosis and how they performed on test scores, or how they performed on tests of cognition. So really, it shows that there's kind of a larger process going on when people develop epilepsy and have a little bit of cognitive deficit. There's a bigger picture. So it's not… you can't just blame that seizure that they experienced 3 months ago on poor test performance. There's more to the picture than that.”
Intro
00:34 Torie Robinson
Loads of us with an epilepsy have depression, anxiety and memory problems. But here's the weird thing - well, actually, it’s not so weird once you understand it - and that’s that some of those problems can start before we're diagnosed, before we start having seizures, and for some people, it’s not the seizures that are causing these problems! I'm Torie Robinson and today I'm joined by epileptologist Dr. Jake Pellinen, whose latest research suggests - and experience tells us - that seizures really are NOT the whole story!
01:02 Torie Robinson
So thank you for joining us today. Could you tell us a little bit about who you are and what you do, please, Jake.
Meet Jacob Pellinen
01:07 Jake Pellinen
Hi, yeah, I'm Jake Pellinen, I'm a neurologist and epilepsy specialist at the University of Colorado and Denver. Thank you so much for having me back on the podcast.
Cognitive testing: The Human Epilepsy Project
01:17 Torie Robinson
Absolute pleasure. So, your Human Epilepsy Project has been going onwards and upwards. So since we last spoke to you, have you uncovered any sort of new evidence that epilepsy might be affecting the way that people think, our cognition and our memory prior to being diagnosed, which could be years in advance?
01:35 Jake Pellinen
Yes, that's a great question! And we have done some follow-up studies and analyses on the Human Epilepsy Project since we last spoke. The first time I was on your podcast, we talked a little bit about the brain changes, the brain structural changes. Following that I looked at a lot of the cognitive data from the first human epilepsy project. Now this study had finished enrolling several years ago at this point and concluded several years ago at this point. So what we're doing now are secondary analyses of the data set. And as part of that study, they utilised something called the Cogstate Brief Battery, which is a short online self-directed cognitive test that will take study participants maybe up to 15 minutes to complete after they've been trained how to do it. And for the Human Epilepsy Project, that was the first study that utilised cogstate in people with epilepsy or epilepsy clinical trials. And so we had a little bit of groundwork to do looking at how well people did on it. You know, was… did… were they able to complete it in a self-directed fashion as part of the study? And what were the results of it? So, a lot of people had normal EEGs and normal MRIs and… that were enrolled into the study. And the question was, did they have any changes that were picked up in the in the cognitive testing? So, as kind of a brief overview, these were otherwise healthy people who developed focal epilepsy in adolescence and adulthood, and then the human epilepsy project collected a lot of data and different types of testing for them.
03:24 Torie Robinson
What are the numbers from this project then? What have you learnt?
03:26 Jake Pellinen
Out of the… all the participants who enrolled in the human epilepsy project, 249 people completed this online, self-directed, cognitive testing, which was over half or almost two thirds of people who would have been eligible to take it (meaning they were either English or Spanish speakers and capable of reading the test questions and taking the test). And so, we did find that it was an effective way to get cognitive data in this large dispersed clinical trial environment. There were a couple of barriers to participation when we're looking at who the participants were that completed this. And so, interestingly, male participants completed it at higher rates. Primary English speakers completed at higher rates. The participants who were black or African American did not complete it as much, so that was something to consider when interpreting the results, as well as people who had reported histories of learning difficulties in childhood didn't complete it at high rates.
04:46 Torie Robinson
Mmm.
04:46 Jake Pellinen
So that kind of skews the sample size a little bit, but overall it was utilised effectively as a test measure.
04:53 Torie Robinson
And what sort of questions - just for people who aren't overly familiar with what “cognitive” or “cognition” means - what were you kind of asking people what were you seeking?
Types of cognitive testing used
05:01 Jake Pellinen
In more formal cognitive testing, we would do something called neuropsychological testing, which can take several hours, and that's kind of the gold standard for cognitive testing. But [it’s] impractical to use in a large clinical trial. So in a clinical trial environment, it's helpful to have shorter screening questionnaires. And in the Human Epilepsy Project, the Cogstate Brief Battery was used, and that included 4 brief tests. One testing psychomotor function (which is a detection test), one looking at working memory through something called a one-back test, one looking at attention through an identification test, and one looking at visual learning through a one-card learning test. So, it used kind of a universally recognised visual cue or of a plane card and did several cognitive tests based on that. So, it was easy to use, understandable, and a quick way to screen people, and they could do it on an online platform at home. They were just told when to do it during the study.
06:13 Torie Robinson
Cool, so they didn't have to come in anywhere and do it. They could all just do everything remotely.
06:17 Jake Pellinen
Correct. So that was kind of unique for this. I think that was the first time something like that had been done in an epilepsy trial before..
06:26 Torie Robinson
You would think that you would get more people taking part - well, ideally - if it was remote, do you think? Was there any evidence?
06:30 Jake Pellinen
Ideally, but you know, there was evidence that less, you know, less people participated in the online remote data collection than those who participated in person with other test questionnaires. So, it was, you know, people in when they came into the office they would complete everything in the office and then there would be a little bit of a drop off when you asked them to complete things at home.
06:55 Torie Robinson
Okay, I guess I see both ways. I suppose on the surface it sounds… “Oh, I'll do it from home, it's all easy!”, but you don't have anybody looking over you, pressuring you or anything like that. Was there anything surprising that you found out about people's cognition?
Results: cognition and epilepsy
07:08 Jake Pellinen
Yes. When we looked at the cognitive scores themselves (so how people actually performed on these measures of cognition), there were some statistically significant deficits in the Human Epilepsy Project cohort, compared to normative data. It wasn't quite what we would consider “clinically significant”. So a neuropsychologist might not consider that to be a big, clinically significant difference, but, on kind of the scale of the test itself there was a difference that was notable. And so when I looked at that and when we analysed this compared to whether or not those scores were associated with treatment resistance, there wasn't an association with that, which is reassuring. And there wasn't a big association between the number type of seizures people had prior to diagnosis and how they performed on test scores, or how they performed on tests of cognition. So, really, it shows that there's kind of a larger process going on when people develop epilepsy and have a little bit of cognitive deficit. There's a bigger picture. So it's not… you can't just blame that seizure that they experienced 3 months ago on poor test performance. There's more to the picture than that.
What might be causing the cognitive problems?
08:34 Torie Robinson
So, it all sounds, maybe this is me, it sounds almost like even more vague, like we really don't know at the moment what's happening.
08:41 Jake Pellinen
There's probably multiple things that explain it and it's related a lot to what whatever caused the epilepsy to occur, you know, and that underlying aetiology that drives the development of a seizure eventually, likely also gives rise to some specific cognitive impairments, and things like comorbid mood disorders and depression, which has been studied a lot in in the literature as well. So, these things kind of arise in parallel. Sometimes depression crops up before seizures. Sometimes cognitive issues arise prior to the first seizure of life. And so seizures are one manifestation of a network disorder.
09:27 Torie Robinson
I could not put it better myself. Exactly, exactly. So are we, do you think that at the moment we're not doing the right tests to actually identify specific abnormalities or what might be causing what, or is this data still available in the project and you're going to be working on that going forward?
Clinicians must take a holistic approach in care
09:44 Jake Pellinen
Yeah, I mean it's certainly something that we'll continue to look at and how that cognition changes over time over the course of the study and across different cohorts. There's two other human epilepsy projects looking at different types of seizures and epilepsy. And so there's a lot of unanswered questions that we'll be exploring. The results of the these analyses highlight the fact that as a clinician it's important to take a very holistic approach when you're meeting somebody with new-onset epilepsy because that seizure could just be the tip of an the tip of the iceberg and it's important to assess for cognitive issues and mood disorders early on, to individualise a treatment plan and figure out how you can support somebody. Obviously preventing further seizures is a huge part of your job as an epileptologist, but there's other things as well that are important to consider.
10:41 Torie Robinson
So we need to be looking at everything that's part of the picture to not just control seizures but to improve how a person feels, their quality of life, how they experience things day to day or hour to hour or whatever it might be because everyone's so different.
10:57 Jake Pellinen
Yeah, absolutely. And I guess the one reassuring part about the findings and from the Human Epilepsy Project were that those “time-limited seizures” (so not like status epilepticus, but time limited seizures that people had experienced leading up to their diagnosis) didn't have a significant, you know, you know, permanent impact on their cognition (that we could see). So it was, you know, people had a seizure, they were able to recover from it and perform well on cognitive tests overall. So I think that is relatively reassuring.
Cognitive issues with other causes
11:36 Torie Robinson
It is, but then doesn't that sound slightly contradictory to the fact that, or maybe this is just something alongside it, but the fact that some people do experience memory issues and cognitive issues before diagnosis.
11:47 Jake Pellinen
Yeah, they certainly… well it's certainly a complex picture. So that… what we did was kind of take the seizures in isolation and the cognitive scores, and then we corrected the scores for other variables like depression. And so when you isolated the effect of the seizures alone, it didn't have a big impact. But when you include everything else, then there is a difference. So which highlights, like, yeah, obviously we need to be important we need to take note of seizures and do our best to prevent them, but there's these other factors and the bigger picture that comes into play when you're looking at cognitive function.
Depression doesn’t cause epilepsy!
12:27 Torie Robinson
Do you know what, I had somebody ask me recently, I, and I think it was after listening to your first episode “Well, I had depression and anxiety prior to my diagnosis.”. And then there was some sort of, one implying that other people should they keep an eye out for potential epilepsy because they have depression and anxiety and other things going on.
12:51 Jake Pellinen
Well, I think, you know, depression is a widespread issue. It's certain you know, if you have epilepsy you're at higher risk of having depression and anxiety, but so many people with all sorts of things that I see in clinic, especially when I'm in general neurology clinic and not just seeing people with epilepsy, they also have depression at very high rates. So I wouldn't say it's exclusive. It certainly is an issue that needs to be addressed, and we need to be comfortable discussing it in clinic. But I wouldn't I wouldn't say that you need to start being concerned, you know, about everything else that could be going, you know, all the other possibilities if you have depression that probably just give you more anxiety.
13:40 Torie Robinson
Well, indeed. So from this, what's the important message that we have for people with an epilepsy, whether they've been diagnosed or not, if they're just interested and the same for clinicians?
Cognitive challenges must be addressed with all other symptoms
13:51 Jake Pellinen
I well I think that the bottom line with some of these additional studies that we did with the Human Epilepsy Project is it really reinforces what other people as well (other investigators in the UK and Finland and elsewhere) have found in new-onset epilepsy is that cognitive function can be a big part of the initial presentation in in the sense that things like depression can affect it, depression can arise in in parallel with seizures, and so all of the different issues that that go into impacting quality of life can arise in parallel and be addressed early on - along with obviously starting an antiseizure medication for people who need it. But, I think that just blaming, you know, a time limited seizure, so you know, a 1 minute seizure a couple months ago or something isn't the full explanation of why you would have some cognitive clouding now, you know, 3 months later. There's probably other things going on. So that's kind of the… what I mean about taking a holistic approach when addressing new diagnoses.
Terrible experience - what a clinician should not do!
15:14 Torie Robinson
So, I suppose if you're a clinician, I'm thinking of an awful experience I had years ago and it was with somebody... I went into my appointment “How many seizures are you having?” “I'm not quite sure because I'm having seizures and I’m doped up on medication.”. Oh “Do you remember your medication?”- “Don't think so, probably not because you gave me medication that probably made me forget it, but I'm not sure.” And then [they said[ “Well, I don't know what's happening then.” and see you later.
15:38 Jake Pellinen
Haha.
15:39 Torie Robinson
Haha! Pretty much!
15:40 Jake Pellinen
I'm sorry to hear that!
15:40 Torie Robinson
Haha! And I do hear this from quite a lot of people. So, I think we, you know, would hope that people, clinicians will listen to what you've just said and kind of see that broader picture - because at the end of the day, we want people to want to live, not just as you say, control their seizures.
Appointments: topic could be depression or memory - not just seizures
15:56 Jake Pellinen
Yeah, no, I mean I have… I have had the experience over many years now in clinic where the main thing that we talk about in appointments is not, you know, the seizure frequency or you know, that sort of thing, it's people wanna talk about memory, people wanna talk about cognition, people wanna talk about depression. And so that that's a huge part of the picture. Because what we're really trying to do and what we should be trying to do is improve quality of life.
16:26 Torie Robinson
And I think every person who has or is affected by an epilepsy, take this information to your appointments. Would you agree? Like…
16:32 Jake Pellinen
Yes. Yes.
16:32 Torie Robinson
…if you are, you are deserving of having the whole picture looked at.
16:37 Jake Pellinen
Absolutely.
Closing thoughts and thanks
16:37 Torie Robinson
So we - people with an epilepsy, carers and clinicians - we need to be looking beyond seizures when it comes to symptoms and when it comes to people’s quality of life.
And as Jake said, memory problems, mood difficulties and cognitive changes might be part of a way bigger picture. And if we only focus on seizure counts, we could easily be missing things that matter enormously to people in their every day lives. If you enjoyed this episode - please subscribe to our channel as you’ll find heaps more like this one! And a huge thank you to Jake for chatting with us and sharing the latest findings from the Human Epilepsy Project!