Ep. 180: Cognitive problems in Multiple Sclerosis

00:00:00: Welcome to EANcast, your weekly source for education, research and updates from the European Academy of Neurology.

00:00:15: Hello and welcome to the EANcast Beacon Neurology.

00:00:18: My name is Yildiz Diggermanji and I'm an associate editor of the e-learning platform of the European Academy of Neurology EAN Campus.

00:00:25: And my guest today is Professor Hanika Hoest.

00:00:29: She is a professor of neuropsychology in health and disease at Leiden University of the Netherlands and will take up the role of director of the Center for Brain Research at the University of Auckland, New Zealand in December.

00:00:41: She's internationally recognized for her research on the mechanisms driving cognitive impairment in multiple sclerosis and how neural rehabilitation can enhance brain plasticity, cognition, behavior and quality of life.

00:00:55: It's a very cool research topic indeed.

00:00:58: For today, she's gonna talk on cognitive problems in multiple sclerosis.

00:01:03: Welcome, Dr.

00:01:04: Hells.

00:01:05: Thank you, I yield this for having me here.

00:01:08: It's a pleasure indeed.

00:01:09: So, let's start with some introductory topics.

00:01:15: We know that many people associate multiple sclerosis with physical symptoms, but cognition is increasingly recognized as a big part of the picture, right?

00:01:25: So, how common are cognitive problems in people with MS?

00:01:29: Do all the patients experience them?

00:01:31: Can you just give us a brief overview?

00:01:34: Yes, sure.

00:01:35: So, I think it has been a long sort of ignorant.

00:01:38: So, I think Sherko, who first wrote about multiple sclerosis, already mentioned symptoms like slowed processing speed, problems with memory.

00:01:49: But I think for a long time, we were also thinking people with MS are usually... rather fatigued and perhaps that may be the reason why they also experience problems with their cognition.

00:02:01: But in fact, we know that around fifty percent, the percentages are not that clear, do actually also develop like true cognitive impairments, which usually results in problems with information processing speed, with memory loss, both verbal memory as well as visual spatial memory.

00:02:21: But also the more, yeah, there are also more higher order cognitive functions that can decline, usually a little bit later in the disease.

00:02:31: But it's approximately fifty percent of the patients that do experience these problems.

00:02:36: And I think the important thing is that it's usually quite subtle.

00:02:42: So it is really an invisible symptom.

00:02:46: also to patients themselves and that makes it hard to recognize.

00:02:49: for neurologists but also for patients themselves.

00:02:53: It is very exciting to hear that because even if the symptoms are subtle, the frequency, the rate is quite high, isn't it?

00:03:02: In terms of cognitive problems in multiple sclerosis.

00:03:05: You already mentioned the different domains of cognition right now, but which cognitive domains are most affected in multiple sclerosis?

00:03:16: I think the most prominent and the most well-known is really the information processing speed that is slowed down.

00:03:24: And this is something that we just recognize in patients that they are slower in responding.

00:03:30: So nothing happens to their IQ, they are just... being able to have the same difficulty of tasks, it just takes them more time.

00:03:39: And I remember when I started, I'm a neuroscientist, and I remember when I started doing neuropsychological evaluations on people with MS, that at the start of the investigation, I said, well, we're about to do some cognitive tests, but maybe you can fill out the reimbursement form first, then you fill it out, I set up all the things that we need, and then we can make a start.

00:04:01: And then the patients were not taking up the reimbursement form to fill it out but they were just staring at me and I thought maybe I have to repeat it and sometimes I have to admit I was a little bit impatient.

00:04:13: so I was about to start the assignment like please fill out the form.

00:04:19: but then I realized that it is actually happening.

00:04:21: it's just with a little delay.

00:04:24: I think what's important to realize is that in current societies, there is not really room for being slowed down.

00:04:31: We're all really on a high pace.

00:04:34: Everything needs to happen fast.

00:04:35: And if you're slow but still capable, that can give you quite some problems in daily life, in work, in your family setting.

00:04:45: So it has a huge impact on the whole social, also the social functioning of people with multiple sclerosis.

00:04:54: And then I think next to the information processing speeds, we do see problems with verbal memory and visual spatial memory.

00:05:01: So really like the list learning, like remembering things that are concerned with language, but also like, where did I leave my keys?

00:05:11: Where in the room is everything located?

00:05:14: And these are the domains that are especially the first that we can detect when the disease has been diagnosed.

00:05:24: Indeed, these problems also can affect the daily living activities or quality of life of patients as much as the motor and sensory symptoms of a mess, right?

00:05:35: As you described, so I was wondering about the underlying changes of pathologies that drive these cognitive problems.

00:05:44: What's actually happening in the brain?

00:05:46: Why are these all happening?

00:05:47: What's the pathophysiology underlying these cognitive problems?

00:05:52: A little disclaimer, I do not have the complete answers, even not after studying this topic for over fifteen years.

00:05:59: But I think what can be assumed and what we know is that the demyelination, that is usually one of the first symptoms or the first pathological changes that we detect.

00:06:13: that that has something to do with the information processing speed.

00:06:16: It's really like the integrity of the white matter, it has been decreased and as a result your cognitive functions will be hampered and especially the speed signals can travel from one brain region to the other.

00:06:31: So the processing speed is really related to this white matter damage that we see early in the disease.

00:06:40: On the contrary, I think most of our cognitive functions, whether it's memory function or executive functioning, that's highly dependent on the gray matter regions in the brain, like the thalamus, hippocampus, or the dorsolateral prefrontal cortex.

00:06:55: And I think it's especially these gray matter regions that in the pathology of MS, usually several little bit later from pathology, which is then not necessarily or only partly demyelination.

00:07:08: We noted all these grey matter regions do have some sort of myelin content as well.

00:07:14: But more prominently, it's the neurodegeneration or the axonal loss that actually occurs in these brain regions and data has been associated with these other cognitive functions.

00:07:27: This is also clearly demonstrated that we see cognitive decline in all disease stages of MS, so in the relapsing remitting phase or the progressive phases, but we do see that cognitive problems become more prominent when the disease enters the more progressive stages, where we also assume that there is more neurodegenerational going.

00:07:51: Now, I see that it's rather quite complex pathophysiology underlying development of cognitive issues, as you just mentioned.

00:08:00: But again, coming to the clinical basis, we see that there's some variabilities between the individuals.

00:08:07: What I'm talking about, some people with MS develop cognitive issues quite early on, while others hardly notice any changes.

00:08:14: I do think there are such differences in between the individuals.

00:08:19: who are affected by MS.

00:08:24: Yeah, this is a tough question.

00:08:25: And I think MS is in particular this order that is so different for each and every individual.

00:08:32: First and foremost, because the pathology occurs random in different brain regions.

00:08:38: So I think it is slightly dependent on where in the brain is the pathology located.

00:08:44: But at the same time, we have other more basic neuroscientific starting point, so to say, so we have something called brain reserve and cognitive reserve.

00:08:56: So we know that persons with multiple sclerosis that have a higher education that they are usually or somewhat more protected towards cognitive decline.

00:09:08: This is not particular to MS.

00:09:10: We also see this in diseases like Alzheimer's disease where people with higher education, they have some kind of buffer capacity, which sort of protects them or prevents them from cognitive decline and the onset of that.

00:09:26: And at the same time, if you have higher brain reserve, so literally more brain matter, you potentially have more options to circumvent a pathology that is present due to the disease, which also allows you to compensate for a pathology.

00:09:47: And that is different for different individuals.

00:09:49: So we see that higher intelligence or more enriched brain networks are protective towards cognitive problems.

00:10:00: One of the questions that I was thinking of is whether they develop early on due to the process of the disease or at the latest stages.

00:10:13: Do these cognitive problems really mean for the daily life of the patients?

00:10:17: How do these cognitive problems affect things like work, social relationships or independence?

00:10:25: What can you say more about the impact of the daily living activities of these problems in patients with MS?

00:10:33: This is a very important question and I would really like to start with an anecdote.

00:10:41: This was years ago.

00:10:42: I was having a conversation with a person with MS in and his partner.

00:10:48: And I was explaining them that cognitive problems are part of MS and that it can occur to, well, as a consequence.

00:10:57: And then his wife actually said to me, well, it's so sad that we didn't notice sooner because it probably would have saved us five years of relationship therapy.

00:11:09: And that was really to me a shocker because I figured like how can it be that this couple was in couples therapy for over five years.

00:11:20: And she said I thought he wasn't interested in me because every time I told him that I was about to do something he forgot about it or he never asked afterwards like how did it go or how are you doing.

00:11:33: And I felt so sorry for them because this is an example that it's not your professional life only.

00:11:40: It is also really in your social environment.

00:11:43: The person that's closest to you is not understanding why your behavior is in a certain way and you don't even know yourself that that behavior is part of the disorder that you're suffering from.

00:11:55: So that is in a more private setting, but I think what we also hear a lot is that people especially early after the diagnosis, they are usually still in a paid job with certain tasks and certain tasks are time sensitive.

00:12:11: Well, and I already mentioned to you at the start, like information processing speed is one of the first domains that we see declining.

00:12:18: But if you're on a time sensitive task and you become slower, it may result in the fact that you cannot finish your job in time or that you're not able to manage your deadlines.

00:12:31: because people are not recognizing it as part of the disease and usually are not talking about it.

00:12:36: Your colleagues may actually perceive you as well, how it is being a slacker that you're not really on top of things, but you're actually incapable of doing that.

00:12:48: And the pain for me is that I think if you would reorganize the tasks and make them less time sensitive, and I'm aware that this is not... possibly in all kinds of jobs but for some persons it may be able to shift the tasks that you're given and because they are less time sensitive you can still fulfill them to perfection without being perceived by your colleagues as not being competent.

00:13:17: And what you usually see is that because people are not recognizing it as being part of a mess this actually escalates towards a conflict at work.

00:13:28: And once you do have a conflict and you do have this diagnosis, it's very hard to get back into a normal situation where you have just a toss.

00:13:37: And I think therefore, it's really, for me, important to talk about it because if you recognize this early on, it can, well, at least guide you in your relationship.

00:13:48: It can guide you at work.

00:13:49: It can guide you within your friendships.

00:13:51: And I think for a person with a chronic disorder like MS, this social network and all these aspects that give fulfillment to life are very important and we can guide people in working through these problems.

00:14:08: I totally agree.

00:14:09: This is really a great and great anecdote, showing us the importance of earlier recognition of these, you know, cognitive problems in people with MS to cope with the disease and cope with, you know, these symptoms as well indeed.

00:14:22: So... Coming to the coping mechanisms or the early detection first, let's go on with the early detection first.

00:14:30: What can we do as clinicians or other healthcare professionals to detect the cognitive problems?

00:14:37: Are there any specific batteries, tests or assessments for the early recognition and detection of the cognitive problems in MS?

00:14:47: Because at the end, we have to support these people who are suffering these... with complicated problems.

00:14:57: Yeah, it's an excellent question.

00:14:58: And I'm very happy that you're asking me this.

00:15:01: And I think if you have limited time, limited resources, I would say, don't make it too hard for yourself, but just ask.

00:15:11: Ask the person, like, do you experience problems with your thinking, whether it's slow thinking, whether it's probably with your memory, do you experience something?

00:15:22: or has it changed lately?

00:15:24: I think a change from before is actually quite informative.

00:15:30: I think nowadays, if you have a little bit more resources, we do have a screening battery.

00:15:36: It's called the BICAMS, the Breathe International Cognition Assessment.

00:15:45: I forgot the abbreviation, but it's a screening battery consisting of three tests.

00:15:50: It takes in total fifteen minutes.

00:15:54: And you do have an impression about how people are doing on information processing speed, verbal memory, visual spatial memory.

00:16:01: And if you do not have the time to do the fifteen minutes battery, you can also stick with only the information processing speed task, which is a symbol digit modality test.

00:16:12: It only lasts ninety seconds.

00:16:14: And you can get some kind of idea like how does this person perform.

00:16:19: according to the norm.

00:16:22: but more importantly if you follow your patient over time how many points does this person drop within a year or within two years?

00:16:31: and we know that if this is a drop of more than seven to eight points that there is an indication that something goes wrong also in daily life and that gives you even a stronger intuition that you may want to either talk about it or refer this person for extensive neuropsychological evaluation.

00:16:50: but I think with the screening tests we can really do already quite the first steps that are helpful in determining who needs a referral and who doesn't.

00:17:03: Now very nice suggestions for the clinicians that they can do these bedside examinations briefly as well to recognize the first symptoms at least right.

00:17:12: and

00:17:13: What I find as much important as the clinician perspective, let's look from the patient perspective, from the perspectives of patients with MS dealing with cognitive problems.

00:17:24: What can you tell them to do to maintain or even improve their cognitive health?

00:17:30: What can they do?

00:17:34: I

00:17:35: think This is a difficult question and it's sort of, we are now narrowing down to where science provides us with a little bit of answers, but not completely yet.

00:17:48: But I think if you really zoom out to a little bit more meta level, I think we're having initiatives like brain health, like how do you keep your brain healthy for all people, independent whether you have a diagnosis or not, which consists of.

00:18:07: make sure you have enough exercise, make sure you challenge yourself on a cognitive level or mental level, but also eat healthy.

00:18:15: Make sure that the whole package is something that you adhere to, to keep your brain healthy.

00:18:25: And I always say to people that suffer from MS, these brain health guidelines become actually even more important if you do have a chronic neurological disorder.

00:18:36: So everything in that end will not damage your brain, so it may be helpful.

00:18:42: At the same time, I do have a lot of patients that have more specific questions and they are kind of unsatisfied with the brain health guidelines.

00:18:52: And then there is I think a little bit of proof within the scientific literature that states that cognitive training, like programs like BrainHQ, for example, where people can train different cognitive domains, indeed will result in better performance in these domains.

00:19:12: So yes, you can train on a computer.

00:19:16: It's like puzzles.

00:19:18: they try to make it attractive with kind of colors and gamified exercises.

00:19:25: For some people that really works very well and it wouldn't hurt.

00:19:30: So you can, if you feel like you want to do something, you can try it and see how it works.

00:19:36: What we do see in the scientific literature, and this is also a little bit a drawback of how our studies are set up, that we actually do see that you can train the cognitive domain, but we do not always see changes in daily life.

00:19:51: So the translation from the computerized program towards improvements in daily life, they are less well known, but also less well studied.

00:20:01: So I think this is really a research gap that our society still needs to tackle in the near future.

00:20:09: But I think the brain health and the computerized trainings can be something that if people want to and are very eager to work on it is something that I usually advise them to do.

00:20:23: Lovely, great recommendations and I'm happy to see that you know brain health mission and brain health prevention strategies are playing the pivotal role also in maintaining cognitive health and even improving the cognitive problems in patients with MS as well.

00:20:39: So you are the expert and you are spending a lot of time on your researches and cognitive problems in MS.

00:20:46: As we hear, brain training and cognitive rehabilitation are also mentioned as possible solutions.

00:20:53: Your thoughts are very important on this.

00:20:54: Do they really work?

00:20:56: What does the evidence tell us about these strategies?

00:21:02: Well, I think the strategies and then we're really talking about compensatory strategy training.

00:21:07: I think that really works.

00:21:09: I mean, it depends a little bit on your definition of what do you mean with if it works.

00:21:15: I mean, if you are very forgetful and you go into a session of cognitive behavioral therapy learning on compensatory strategies regarding related to memory, you will indeed or less forgetful.

00:21:31: but that is because you learn how to use a diary how to use your phone to remember things to set up reminders.

00:21:39: so yes it helps in daily life but it doesn't mean that your brain has improved.

00:21:46: it's just like you.

00:21:48: if i put it very bluntly You learned tips and tricks to circumvent the problems that you experience and in the end that results in a better functioning in your daily life.

00:21:58: And that's very, that people really appreciate these kind of interventions.

00:22:04: It's a psychological intervention.

00:22:06: Then if you go to the more functional training strategies where you really try to see if I train the memory function, do I see better performance of the hippocampus?

00:22:18: or is the hippocampus has that obtained more brain cells or did it grow?

00:22:24: Then the evidence isn't there in humans.

00:22:27: So we know from animal models that brain tissue can actually grow and there is neuroplasticity.

00:22:36: But in humans and in MS patients, we do not know, we don't have the proof, but we do see that cognitive test scores can improve.

00:22:45: And we're currently at the stage where we really have to see how does that work.

00:22:50: And I think one of the newest insights from my team is that we actually see that if you do brain training to really try to enhance the brain and the brain network.

00:23:04: that that is something that we see that happening in people with MS that do have brain networks and a functioning of the brain that is most likely due to that of healthy controls.

00:23:18: So it seems that the brain is most susceptible to change and to creating new connections when there is not too much pathology yet.

00:23:29: And this is a very important finding, in my opinion at least, because I think this sort of leads toward a paradigm shift that we actually should try to get to cognitive rehab or maybe rephrase cognitive rehab towards a more preventative type of intervention where you try to enhance brain functioning before the cognitive decline actually has become a problem.

00:23:56: So it is sort of like... secondary prevention.

00:23:59: You do know you have MS.

00:24:01: There is a fifty percent chance that you may develop cognitive decline.

00:24:07: But when it's not there yet, you may actually have the best circumstances to benefit from cognitive rehabilitation programs.

00:24:16: And that's what we currently are in the middle of studying if we're really able to enhance brain functioning when the problems are limited.

00:24:25: Well, great.

00:24:28: I'm fascinated by these strategies.

00:24:31: Thank you so much.

00:24:32: And again, we know that you are literally focusing on cognition, behavior, and as you just mentioned, brain structure and neuronal plasticity in the mass.

00:24:42: So you're doing a great work with your large research group.

00:24:46: You study all of these in the mass.

00:24:48: Can you tell us a bit about, you know, what your team is focusing on right now about the prevention or other issues?

00:24:55: So from the prevention domain, we're currently running a large randomized controlled trial in which we have two active arms and a placebo or a non-interventional arm.

00:25:10: And in the two active arms, one group of these are all patients with multiple sclerosis that still have a paid job for at least twelve hours a week.

00:25:21: They have no cognitive impairments based on the current definition of cognitive impairment.

00:25:28: But we do feel that they may benefit or that we can prevent or at least postpone the onset of cognitive decline or problems at work.

00:25:38: So one of the active arms is giving an intervention at the workplace where we proactively try to think along with the person with MS like how Well, in your circumstances, you're still doing fine, your work is going well, but we know that I think seventy percent of the persons with MS will get unemployed within five years of the diagnosis, which is like a significant problem if you're very young trying to set up a career.

00:26:06: So how can we, well, maybe make people more resilient towards the MS pathology and the influence at work by being proactively guiding them or coaching them?

00:26:17: And if they feel comfortable enough, they can even invite their employer to the coaching sessions.

00:26:26: And the other active arm is really aimed at brain health, where we have an exercise intervention where patients are trained for three times a week.

00:26:35: They get one hour a week brain HQ training to enhance the brain functioning.

00:26:42: And they are guided by lifestyle advice on diets.

00:26:47: And we're following them up for the intervention loss for four months, and we follow them up for a year to see if they, the persons in the active conditions, if they have better brain states, better workability, and better quality of life compared to the usual care group that didn't got any intervention.

00:27:06: So that is one of our biggest studies, a huge line of research.

00:27:11: And the other is, is that, What we do see is that if people are participating in brain or in cognitive rehabilitation, there's usually a lot of other things ongoing.

00:27:23: So I already mentioned at the start of this conversation that people with MS are often fatigued.

00:27:30: They can have problems with their mood.

00:27:32: They have all kinds of problems.

00:27:34: that also interferes with the cognitive performance.

00:27:38: But especially if you're participating in cognitive rehabilitation, It may actually help if you have some kind of preparation time to really prepare the mind.

00:27:49: That's actually the title of our study.

00:27:52: Prepare the mind such that when you start cognitive rehab, you're really in the zone like I'm really going to do this.

00:27:59: I can adhere to the three times a week training sessions to really Make sure that when you start you have all your attention focused on that particular thing that you're Interested in or that you want to work on And we don't know.

00:28:16: so we have this this this study ongoing where one group gets like prepare the minds and the other gets a sham intervention to see if we can prepare the minds and if that leads to larger responses to cognitive rehab.

00:28:32: Amazing I really am so impressed about these research areas because they are so promising, right?

00:28:38: It's going to give us all the clues at the end.

00:28:40: We're looking forward to the results of your studies.

00:28:43: That's really amazing.

00:28:44: I'm fascinated.

00:28:45: Congratulations right now.

00:28:47: We're looking forward to the results.

00:28:49: So I was planning to ask you what can we do to look ahead?

00:28:54: What can you hope for the future?

00:28:56: But you already gave us the hopes.

00:28:59: Maybe you want to wrap up and summarize last button.

00:29:02: not least.

00:29:04: Where do you think the next breakthroughs will come from?

00:29:08: Yeah, that's a good question.

00:29:10: And I feel the pressure yield this, but even from New Zealand, I will be working on these topics.

00:29:15: So that's the good news.

00:29:18: Well, what I think

00:29:19: would be

00:29:20: what we still miss, cognition is a complex, cognition is complex, multiple sclerosis is complex.

00:29:30: So it actually ties into pathology, it ties into work and workability, it ties into your relationships, your close ones, your social interaction, financial independence, sense of belonging and well, being meaningful to life.

00:29:49: And I think what if we really want to progress the life of people with MS.

00:29:56: And then especially from my perspective, the cognition, I think we have to integrate all these different domains in life where people are actually operating and try to find out how things actually tackle into each other.

00:30:10: So I see a lot of patients spending a lot of energy to keep up their work.

00:30:17: but at the same time do not have the time to hang out with their friends while actually your social connections are also important in how you are supported throughout your disease.

00:30:28: So I think a really one-size-fits-always not possible in this regard and we should really try to work on that.

00:30:37: Thank you, Hanneke.

00:30:38: It really has been a delightful conversation.

00:30:41: I'm very impressed with your work as well.

00:30:44: Thank you for being with us today.

00:30:46: It was really enlightening and delightful.

00:30:49: You covered all the community problems from all aspects in patients with multiple sclerosis.

00:30:54: It was a great pleasure indeed.

00:30:56: Thank you so much for having me here and that I could share my story.

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