Aiming for early detection of Alzheimer’s and Parkinson’s

Irena Rektorová is a leading Czech neurologist in the study of diseases that cause brain degeneration, such as Parkinson’s and Alzheimer’s diseases. Together with her team from Ceitec MU, she launched a unique international project this April – one of the best Czech projects in the prestigious Horizon 2020 programme – focusing on brain activity in connection with reading, writing, speaking, and visual signal processing in different cultures.

She received an award from the university’s rector this May in recognition of the success of this grant.

Could you tell us more about the CoBeN project?
It is a research project in behavioural neurology and the main part of the project consists of monitoring patients in various phases of Alzheimer’s and Parkinson’s disease and stroke survivors. We also monitor healthy volunteers while they are reading, writing, and processing speech and visual signals. The unique aspect is that we will be observing people with different native languages: English, Czech, and Hungarian.

In laymen’s terms, you will observe what is actually happening in their brains during these activities?
We will examine their higher cognitive functions and also use MRI, so you are basically right – we will look at the functional and structural connections between different structures in the brain that play an important role in language, speech, and cognitive functions.

Why are you interested in that?
The general goal of our Ceitec research group is to find markers, which are something like indicators and early predictors of the onset of neurodegenerative diseases. The point is to detect these diseases early because if we can manage to diagnose them in time, there is a relatively successful targeted and personalised therapy that can be used. This can involve pharmaceutics, speech and language therapy, cognitive training, or what is known as non-invasive brain stimulation.

What is that?
Repetitive transcranial brain stimulation involves stimulating certain parts of the brain close to the bone using an inconstant pulsed magnetic field. Because the parts are interconnected through neuron networks organised based on the tasks they perform, we don’t only stimulate one area, but the whole network. We know that the magnetic field changes to an electric field, so we really are able to strengthen the functional connections between individual parts of the brain. As a part of our research, we want to study what happens during the individual stimulations so that we can fine-tune our targeting. This could become a common rehabilitation technique, used along with other techniques as part of the treatment.

What are you hoping to discover by choosing people from different language environments?
Reading and writing are different in different languages. In Czech, we read a text more or less the way it is written. Our grammar is more complicated than in English, but for English speakers, reading and spelling are two very different things. This is called surface and deep language. It’s the reason we think that cognitive functions are slightly different in the brains of speakers of different languages and, as a result, certain diseases, and especially a stroke that occurs in the same place in the brain, might not have the same effect on someone who speaks English and someone who speaks Czech or Hungarian. Therefore, any speech and language therapy or non-invasive stimulation provided afterwards would also need to be different.

Would that mean that treatment is also culture-dependent?
It seems likely, but we need to have this corroborated by the research.

What helped you win the Horizon 2020 grant?
The decisive factors were probably our relatively novel idea and the international context of our research. We grounded it in our research goal and our long-term cooperation with the University of Arizona in the US and the University of Szeged in Hungary. Professor Steven Rapcsak from Arizona, a neurolinguist who will supervise the study stays of our students, spent his sabbatical at the MU Faculty of Medicine – as the very first foreign academic – and worked in Ceitec on our MRIs.

How did you manage to put the project proposal together?
The support of the Ceitec Grant Office was very important. Previously, we didn’t have a team of people available to help us write something like that so it turned out to be really helpful. We can, of course, put together the scientific part – but it comes with a lot of paperwork and it was the team who did most of the work in that respect. Jakub Zeman, who deserves credit for a lot of the work, is actually the one who nominated us for the rector’s award, which I received at Dies Academicus.

What result are you expecting from this research?
The main goal is to expand our knowledge in general. However, it is clinical research, so it should have a direct impact on patients. The ideal outcome would be to discover the early disease markers that I mentioned previously and new options that could, at least temporarily, manage the symptoms. Specifically, this could be something to do with articulation and motor speech disorders in patients with Parkinson’s. They often speak in a low voice or slowly, or they can’t articulate properly to the point that they are very difficult to understand, even though they can themselves understand everything – it’s talking to others that’s the problem. We know that for proper speech, it is essential that you hear yourself and there are certain feedback mechanisms in the brain for this, which are often damaged as a result of the disease. In other words, these people speak quietly or suffer from some sort of speech impairment, but don’t think there’s anything wrong with their speech. This is why being able to influence these mechanisms could be an interesting treatment option. It might be even more important than focusing on the motor function of speech organs.

What is the current situation with medicine when it comes to diagnosing Alzheimer’s and Parkinson’s? When are you able to detect these diseases?
We have already made quite a lot of progress with Alzheimer’s, which mainly manifests itself through memory loss. During the early stage of the disease, MRI can show a reduction of the hippocampus, a structure on the inner side of the temporal lobe, which is important for retaining and recalling a memory trace. Parkinson’s disease, whose main symptoms are movement disability, slowness of movement, shaking, and difficulty with walking, and which also often progresses to a cognitive disorder, is a harder nut to crack. So far, we mainly know various non-specific clinical indicators, such as impaired smell, depression, or constipation, but these are all relatively common symptoms in the ageing population.

This doesn’t seem like something that would make you go and see a neurologist.
Almost certainly not, even though an experienced neurologist might be able to diagnose early signs of Parkinson’s. As regards markers from imaging devices, there are already some techniques that can show a reduction in the number of dopamine-producing cells, but only when the disease has progressed to the movement disability stage, not at its onset. Moreover, it is a very expensive examination – it costs about 20,000 Czech crowns, while MRI costs about a thousand. This is why it is now a global trend to try and find something that could be detected using resonances, as MRI is not only cheaper but these days also widely accessible.

And what treatment can medicine offer for these diseases?
There is as yet no causal treatment – that is, treatment of what’s causing the disease – for degenerative brain diseases. In the case of Parkinson’s, we have both pharmacological and surgical treatment for the movement symptoms. However, the situation is much more complicated when it comes to the cognitive symptoms of both diseases. There are drugs that can temporarily, say for a year and a half, halt the progression of the disease, but they can’t improve the patient’s condition. The research of the past 20 years is converging on immunotherapy or biological therapy. This means developing antibodies to pathologic proteins aggregating in the patient’s brains. When we find an antibody that works, and this is going to happen soon, we must be ready to use it in patients showing very mild symptoms, who are clearly in a preclinical stage of the disease. And that’s what we do – we try to find ways to recognise that they are at this stage. Early treatment is more likely to be successful than treatment in later stages, once the unstoppable pathological cascade has already started.

To what extent are these diseases a normal part of getting old?
None whatsoever. It’s true that in the case of Alzheimer’s, the two main pathological changes correspond to the changes that start in every healthy human brain after 40 and then after 50 years of age, but the difference is in the extent of these changes. If we lived to 120, we would probably all get Alzheimer’s, but at the age of 85, it’s only diagnosed in 50% of the population. In other words, this is not normal ageing, this is accelerated ageing and there is certainly something that causes it; we just don’t know what it is. Fighting it is very important both for the patients and for their families. Even now, we can give them several more years of quality life.

Has it been mapped yet which parts of the brain are responsible for what?
The idea used to be that there are certain centres in the brain, such as a language centre or a memory centre, but now we know that it’s not that simple. Even though certain parts of the brain play a bigger role in certain activities, we know that they can be substituted. Our project works with the fact that the human brain has incredible plasticity and the ability to regenerate and to find another path, because it doesn’t work as a series of centres, but uses complex networks. These can be both specialised and very general. The general ones supervise the performance of some tasks, but can also take over when there’s a deficiency somewhere else. A stroke is a good example. The areas of the brain directly impacted by a stroke are lost, dead. But unless you suffer another stroke, the remaining areas can step in or regenerate. People who lose the ability to speak after a stroke will learn to speak again after a while. Maybe not as well, but they will – and they will do that on their own without any treatment. Understanding these mechanisms can turn out to be very important in the future.

Your position means you are simultaneously a physician, a scientist, and a teacher. It sounds like a great combination, but isn’t it a bit demanding?
It’s awfully demanding. It’s certainly good training for the brain, so it serves as good disease prevention and helps me avoid burnout because these activities are very different from each other.

What do you like doing most?
That’s a difficult question. I like teaching and it’s also a way to get talented young doctors for the clinic and scientists for the lab. I really like the P-pool project of the MU Faculty of Medicine, which involves talented students in scientific work from the first year of their studies. I have five such university students in my teams and they are absolutely amazing. I sometimes find it shocking how motivated they are and willing to spend all their free time in the lab. When I was a student, we spent a lot of time in pubs and doing a lot of other things, but they don’t – they really work like dogs at Ceitec or at the hospital.

What is the connection between your scientific and medical work? Do you apply your results in practice?
I work in clinical research, which is a field where you work with patients from the very beginning, so the connection is absolutely essential, and I like it that way. I don’t think I’d enjoy working just as a clinician – that would be quite depressing in the long run. It gives you a bit more motivation if you combine this with research and do your bit for the advancement of the whole field.

What do you like about neurology?
The brain is an infinitely interesting organ. I could have probably got excited about some other specialization within internal medicine as well, but when it came to choosing, the team of people I worked with in my first job in Prague played a huge role.

Are you also able to get your students excited about your field?
I hope so, but neurology is a challenging discipline and many students don’t like it. I’m trying to motivate them by explaining that it’s beautiful in that you need to make connections between what you know and you need to think. This, however, is exactly what some people might not enjoy. Young med students often want to do acute medicine, where there are relatively clear pathways for what you should do, if... It’s not quite like that in neurology. Of course, there are areas like strokes, where such pathways exist, but my specific area of interest – neurology of neurodegenerative diseases – really is about making connections between individual pieces of knowledge and thinking. Often, the only tools at your disposal to make a syndromological diagnosis and find where the lesion is in the brain or the spinal cord, or whether there are more of them, is a neurological hammer and the patient’s medical history. I’m exaggerating a little, of course, but I always want the students to get as far as they can using only these tools. This is what I see as my main role now: teaching the younger ones and motivating them for further work and successes. And naturally, also to seek out grant opportunities and obtain funding for future research.

Don’t you sometimes feel sorry that you are no longer “in the trenches” of research?
Of course I do. I sometimes keep some data for myself, to process it and get it published, but I have less and less time for that. I have to devote time to my teams and my projects, meetings, and organising. But what I really love to do is meet with my PhD students over the results, interpret them, give them some advice, form hypotheses.

Do you have a specific ambition?
It would certainly be great to contribute with something that will move the treatment forward for the diseases that I work on. But clinical research isn’t something you get a Nobel Prize for if that’s what you mean. Nobody has achieved that yet. It’s rather for those who work in experimental research at cell level. We are closer to the patients and applications, so we can see the results of our work quite quickly but it’s not basic research that would move the whole discipline forward. That’s a task for someone else.

Masaryk university