Katerina Sheardova, M.D., Ph.D. will now represent the Czech Republic on the European Academy of Neurology (EAN) panel on dementia. Her main goals within this platform include focusing on clinically available early biomarkers of the disease and strengthening research on lifestyle-related risk factors for dementia and promoting them as a preventive measure to the general public.
We asked in a short interview how these goals relate to research within the Cognitive Disorders and Dementia Research Team of the International Clinical Research Centre of St. Anne’s University Hospital in Brno (FNUSA-ICRC).
You have been researching neurodegenerative diseases for more than ten years. Are the goals you have set for yourself as a representative of the Czech Republic on the EAN Scientific Panel related to your existing research or is it an extension of it?
Yes, it is very closely linked. As an example, I will mention the Czech Brain Aging Study, which is a preventive study, involving people who already have a memory problem but have not yet developed dementia. The difficulties may be subjective or measurable by sensitive psychological tests, we call it mild cognitive impairment. We monitor over time how their memory deficit develops, how the MRI findings develop, and possibly biomarkers from their cerebrospinal fluid. We also focus on some lifestyle indicators, analysing, among other things, how lifestyle affects the rate of brain cell loss or the risk of dementia.
Another intervention study, the results of which we published in Clinical Interventions in Aging, I would like to follow up on, was on mindfulness, which is the ability to fully experience the present moment and to let go of emotions. It was specifically about Mindfulness-based stress reduction therapy, the use of this technique in stress management. It was an eight-week program for patients who were taught to use these techniques in their daily lives, to be mindful of the present moment and reduce stress, which is one of the most significant risk factors for neurodegenerative diseases. It is the reduction of these factors, which can be influenced during life, that we should focus on the most in order not to be at increased risk of dementia. In addition to stress, there is also depression and chronic inflammation in the body, which mindfulness techniques have an excellent effect on, as we have also published. In fact, dementia and neurodegenerative diseases in general are associated with chronic inflammation, which is increased in old age, so-called immunosenescence. When I say chronic inflammation, I mean an increase in markers that we can read in the blood, for example, the activation of certain types of lymphocytes, an increase in certain immunological factors… If we reduce stress, then in addition to inflammation, we also reduce the secretion of stress hormones, such as cortisol, which, when it acts chronically and for a long time, has harmful effects on our organs, including the brain. And if the hippocampus, which is related to memory implantation, is damaged, it can contribute to the development of Alzheimer’s disease. So, to summarise, the research that we are doing is related to the goals that I have set for myself in my role on the EAN dementia panel.
What about your latest research using organoids?
With organoids, which are defacto little brains, these little balls with a structure similar to brain tissue, we are looking at Alzheimer’s disease from a different perspective. Typical of this disease is a pathological cascade of protein clotting. One of these is amyloid, whose function is to protect the brain from infectious agents, i.e. viruses or bacteria. There is a theory that the action of a particular virus or pathogen may cause this protein to clot more than is permissible and thus trigger the pathological cascade. And we’re trying to find which pathogens that might be, and we’re using these “minibrains” to do just that.
So it’s like a cytokine storm, where the immune system overreacts?
Figuratively speaking, we also know that in general, in old age, originally functional proteins are more likely to precipitate, and this is not just amyloid, but also, for example, the Tau protein, which actually accompanies neurodegenerative diseases. So the object of the research is to find out why proteins start to precipitate, because then they stop working as they should. Because of this, cells then start to die, which is manifested by so-called atrophy, i.e. the loss of brain tissue in certain parts of the brain, which then manifests itself in different clinical symptoms, depending on which areas of the brain are most affected. Atrophy can be monitored by magnetic resonance imaging.
What impact do your areas of interest have on patient treatment?”
There is currently a great effort to find drugs that will stop the pathological cascade. But because this disorder starts maybe a decade before a person has clinical symptoms and goes to the doctor, the most important thing is to find these patients early. And this is related to my second goal, which is to find tests that are affordable, clinically accessible and have relevant results. Although we already have ways to test for these specific non-functional proteins, such as amyloid pet, which is an expensive imaging test that is not available to everyone, or they can be detected by lumbar puncture, which is invasive and unpleasant for the patient. The search for biomarkers in the blood is currently being developed so that it would be possible to detect the disease after a blood draw. Another very simple option is special, very sensitive neuropsychological tests that would detect this incipient deficit earlier than the conventional tests used now. Our team specializes in spatial navigation, where the inspiration was research on animal models, which we have translated for use for patients using computers as simulated orientation in an arena to test a person’s ability to reach a destination. Or there are those that combine multiple questions together, such as the FNAME test, where the patient is presented with faces to which they are assigned names and their occupations, and after a certain point the patient has to reconnect the faces with other information about them. There are more of these tests, it’s about finding the best ones.
If I can’t remember the name of a person I know for sure, is that a signal that I should start worrying?
Name dropping is a typical sign of aging, not a pathology. It’s a normal part of being age-related, something we probably all deal with. The test mentioned is not just about names, it is mainly testing the memorability of new information. Which is the problem with Alzheimer’s – we are unable to remember newly presented information. The people tested remember well what they have known for a long time, but they have an impairment in storing a fresh memory trace.
So what should be the main contribution of the topics you propose in the EAN dementia panel?
To summarise, the two aims are linked and should lead to early detection of neurodegenerative disease and then, based on research, to the recommendation of an appropriate therapeutic approach. The more distant goal is that these recommendations should not only serve to detect early those who are already ill, but should also help those who are at increased risk of, for example, Alzheimer’s disease, so that they can take effective measures, whether pharmacological or lifestyle measures, in order to prevent the disease from developing in the first place. I would like to be able to extrapolate the findings further, as prevention of neurodegenerative diseases for the general population.