We all forget something from time to time. But how much forgetfulness is still normal, and when is it time to consider a more serious problem - dementia? Professor Daniela Dieterich, spokesperson of the “The Aging Synapse” research training group at the University of Magdeburg, spoke to us about dementia, a disease that is currently incurable. She tells us what the first signs might look like and explains whether “brain training”, sport and a healthy diet can actually delay the disease.

Our guest today

Today’s guest, Professor Daniela Dieterich, conducts research in the Faculty of Medicine at the University of Magdeburg and is the head of the “Aging Synapse” research training group. Among other things, she studies molecular cell biology and synaptic plasticity in order to develop treatments for the widespread condition that is Alzheimer’s disease. In addition to medical doctors, immunologists and neuroscientists are educated in the Faculty of Medicine at the University of Magdeburg.

 *the audio file is only available in German

The Podcast to Read

Intro voice: "Wissen, wann du wilst." The podcast about research at the University of Magdeburg.

Friederike Süssig-Jeschor: Today we will be discussing a highly emotional topic: Alzheimer's disease. Anyone who has seen the film “Honig im Kopf” (Head Full of Honey) with Dieter Hallervorden, knows that the change in the person affected and the strain on their relatives is highly detrimental. My name is Friederike Süssig-Jeschor, I work as a press officer in the Faculty of Medicine at the University of Magdeburg. I am pleased to welcome Professor Dr. Daniela Dieterich as my guest today. She is the new Dean of the Faculty of Medicine, Director of the Institute of Pharmacology and Toxicology at the University of Magdeburg and spokesperson of the “Aging Synapse” research training group. The University of Magdeburg, the Leibniz Institute for Neurobiology and the German Center for Neurodegenerative Diseases have joined forces within the funding program to support up-and-coming scientists on their way to obtaining their doctorates. These young scientists are conducting research in the field of neurodegenerative diseases. This includes Alzheimer's disease. A very warm welcome, Professor Dieterich!

Professor Dieterich: Good morning! I am very happy to be here.

Friederike Süssig-Jeschor: How did you come to be researching in this field? What do you find so fascinating about the subject of Alzheimer’s?

Professor Dieterich: Even as a child and a pupil at school I found the mental skills that we are capable of amazing, such as learning motor movements - of course riding a bike was a major highlight for me - but also learning to play a musical instrument, playing together in an orchestra, that fascinated me, as well as how it is possible to remember something so very vividly. And then I studied biochemistry and it seemed to make sense to study the molecular and cellular aspects underlying cognitive performance characteristics.

Friederike Süssig-Jeschor: The research training group consists of thirteen sub-projects. That is rather complex and multifaceted. What is the common goal that you are working towards?

Professor Dieterich: How neurodegenerative diseases in old age can be prevented and how they can be treated. In reality, we have asked ourselves the question: what actually happens before a disease develops? Not “how does the nervous system develop?”, that is not our focus, but instead “what happens during the aging process?” Is there a point of no return, by which all points are fixed, that then leads to a disease developing, or can we stop this? This is our question. We did not wish to devote ourselves specifically to one model of disease. Of course, the focus is neurodegenerative diseases, but we decided that we would go a step further back. We are looking in the system before something is no longer correctly balanced and in this way we have defined four subject areas, namely protein imbalances that are present at synaptic points, the contact points between nerve cells. What happens there during the aging process? What role does inflammation play? What role do neuromodulations play? And, of course, we have also included human projects, in which we are looking to see what the influence of certain neurotransmitters during the aging process is. Such as, for example, dopamine.

Friederike Süssig-Jeschor: What types of neurodegenerative diseases are there? Perhaps you could explain for us the difference between Alzheimer’s disease and dementia.

Professor Dieterich: In the first instance, neurodegenerative diseases are an umbrella term for a range of disorders that primarily affect the nerve cells in the brain. Nerve cells do not generally multiply and replace themselves. That is a problem. This means that damaged or dead nerve cells, and this happens continually through life, cannot be renewed by the body. Neurological diseases include, as you mentioned at the start, Alzheimer’s, but also Parkinson’s disease, Huntington’s disease and also the array of forms represented by the so-called movement disorders, the ataxias. Unfortunately, neurodegenerative diseases cannot be cured. This we know. They weaken one’s health and lead to the progressive degeneration and ultimately death of nerve cells. The consequences are movement coordination problems. These are the ataxias, or a loss of mental capabilities that are generally termed dementia disorders. That is the difference and, at sixty to seventy per cent, Alzheimer’s disease accounts for the bulk of dementia cases. And it is one of the so-called primary dementias. In contrast to this, dementias that are due, for example, to a brain trauma or alcohol dependency, are secondary dementias.

Friederike Süssig-Jeschor: According to the World Health Organization, by 2050 there will be twice as many people over the age of 65. Is there a connection between this and the increased numbers of people suffering from dementia? In other words is it down to the fact that people are getting ever older? Or why is this diagnosis of Alzheimer’s being made ever more frequently?

Professor Dieterich: The biggest risk factor for dementias is actually getting older in itself. But it is a combination of getting older, in part also better diagnostics that enable us to recognize more readily that a condition is dementia, but also other risk factors that we have in our so-called western world. That is to say being overweight, alcohol, and above all stress. Women, for example, are more likely to suffer from dementia due to their longer life expectancy. We can see this from the statistics. However their mental decline progresses more slowly, whilst for men it may be a little rarer, but the disease progresses more quickly and its course is more severe. Completely new studies from recent months have shown that perhaps the second X chromosome in women might have a protective effect that is an interesting target for devising a treatment since, as already mentioned, at the moment we cannot cure neurodegenerative diseases. Once the process of disease is switched on, nerve cells die leading subsequently to a loss of as much as 20 per cent of the brain’s mass, and we are unable to prevent it. We cannot replace nerve cells as we could, for example, a liver.

Friederike Süssig-Jeschor: Let’s go a little deeper. What exactly happens in the brain to cause Alzheimer’s disease to develop? What is the trigger?

Professor Dieterich: As already mentioned, the clinical symptoms manifest themselves through a progressive loss of nerve cells, and the consequence of this is the shrinkage just mentioned and associated with this the deepening of the sulci on the surface of the brain, which we can see, together with an expansion of the ventricles, the so-called chambers of the brain. In the intermediate and advanced stages of the disease, this shrinkage can be examined by using imaging techniques the like of which we are able to apply very well here in Magdeburg in several locations and these examinations can then help to distinguish a case of dementia, Alzheimer’s disease, from other diseases that have a similar clinical appearance, for example cerebrovascular diseases. This is subsequently extremely important, including for treatment.

Let us come back to the decline of these nerve cells: what actually happens on a molecular and cellular level? Through this decline, nerve cells lose their contact opportunities, and we all know how important contact is in life. We have friends, we have a social environment and nerve cells are actually also not used to anything else. This means, when your points of contact suddenly dry up, when information is not forwarded, then they feel not only detached, but they also lose their metabolic support and begin to decay. Meynert’s basal ganglion is a very important underlying brain structure in this process. A very important neurotransmitter is generated by the nerve cells here, known as acetylcholine. And perhaps you have already heard of so-called anti-dementia drugs, in other words pharmaceuticals that can slow down the progress of the disease at least a little. These so-called acetylcholine esterase inhibitors are used in the clinic and they cause the neurotransmitters to be depleted less quickly which can delay the disease. And as a consequence, above all of the dying of these cells in Meynert’s basal ganglion, there is a real imbalance. I mentioned this already at the beginning. These changes cause the processing of information to be interrupted and are also implicated in the observable loss of memory. And something that is typical of Alzheimer's disease is that we have protein molecules that clump together. This happens to two proteins, on the one hand to a cytoskeleton protein, the tau protein, which then is present in a hyperphosphorylated form. Hyper, sounds like something where you would say, “that’s exciting,” but for a nerve cell it is really not good, and this causes the formation of what are known as neurofibrillary tangles. Alois Alzheimer, after whom Alzheimer's disease is named, was able to identify these in his patients under a microscope. The second point, where protein molecules suddenly begin to behave abnormally - and we don’t yet know exactly why this happens - is when the so-called “Eb beta” forms deposits, this time outside of the cell. Tau does it inside the cell, and “Eb beta” does it outside. Imagine it this way: if the trash starts to pile up in a street and cars can no longer get through, no information gets through anymore either and you can’t get home. And if you have these problems, these deposits, cells begin to die and that is irreversible. And so we have right now identified two targets, or introduced them to the discussion, that are also currently real targets in pharmaceutical research. There are now antibody studies that show that when in cell culture such cells have these agglutinations not only is it possible to help, but also the first tests with trial subjects show that whilst the clock cannot be turned back on the disease it can be slowed down. This means that it is more and more important to detect Alzheimer’s at an early stage.

Friederike Süssig-Jeschor: You probably also know what it's like: I have to make lots of notes for myself so that I don’t forget anything in everyday life and as a young mother: shopping list, to-do lists, everything that goes with it. Is that already a harbinger of Alzheimer’s, or how do I recognize this disease early on?

Professor Dieterich: So that is completely normal, at least I hope so, because I’m always losing my keys, but dementia as we see it with Alzheimer’s, in the form of age-related dementia, that develops slowly. In the beginning those affected stand out, for example, because they become inattentive more often. They ask the same questions often - people are sure to have encountered this in their own environment or at least from films, or from fiction - or can’t think of the right word immediately when talking. Yes, misplacing objects is part of it too. You might find the remote control in some really strange places like the sock drawer or even sometimes in the fridge. People suffering from Alzheimer’s find it difficult to place a face, sometimes even of people who they have known for a very long time. Another point is that their judgment is simply impaired, for example, they go shopping in their slippers or only put on summer clothing in winter and then catch a chill, and then more complex tasks, like receiving change and then checking it, or filling in forms become more difficult. What comes next is behavioral problems and that is probably also one of the times when relatives notice for the first time that something really isn’t right. For example really gentle people suddenly become aggressive, probably because they cannot cope with the new situation in which they now find themselves. And often this leads to this person withdrawing from their social circle, meeting fewer friends, getting outside in the fresh air less, simply because of this uncertainty. And the suspicion of dementia is really very, very often suggested by the relatives, who notice these behavioral changes and the drop-off in cognitive performance. Those affected themselves sometimes mainly put these performance limitations down to their advancing age and not to a disease. This means that the step to the neurological outpatient's clinic for a dementia consultation very often happens at a very late stage.

Friederike Süssig-Jeschor: Is it possible to speak of a typical progression, or does it differ? You have mentioned that the disease can progress differently depending on the person’s sex. Is it possible to say that there is a typical progression?

Professor Dieterich: Yes, the typical progression, as we have said: losing things, loss of judgment, progressive loss of control of one’s own abilities leading on to a state of confusion that makes independent everyday life no longer possible. Right through to care levels one, two and three, in which the patients really need round the clock supervision.

Friederike Süssig-Jeschor: Shall we perhaps discuss what people who notice that they are unwell can do. Nowadays there are quite a lot of apps that one can use to practice one’s cognitive skills, probably the best known of them is Dr. Kawashima's Brain Training. We are all familiar with them. Our start-up, neotiv, is looking into how the brain can be trained using an app. Another research project at the university is examining the connection between exercise and the performance of the brain using a “dancing walker”. In principle, whether older people who exercise are mentally fitter. Does it help? Can I prevent Alzheimer’s with exercise? And slow down its progress?

Professor Dieterich: Yes! Absolutely! Now I can say to my students, when we come to dementia in the pharmacology and toxicology lectures or in the seminars: Dear medical students! Go into research, we have targets now. Do clinical research, because at the moment we have no, or only inadequate treatment options available to us except for “you must get your patients to be active!” The dancing walker is an example of exercise. Exercise involves motor skills that must be coordinated by the brain, it is input for the brain and it trains the brain. Just like the many brain training apps that are on the market and that is where neotiv comes in, monitoring, training and thus being better able to assess the brain's gradual decline over a long period of time. On the one hand, you can train your brain, but at the same time these apps also provide an opportunity for the first time to receive a warning very quickly: perhaps it would be good to attend a neurological outpatient’s clinic now, perhaps this is an indicator of the onset of dementia. And this also reflects very well the testing in animals that has been carried out over the past thirty years. We have known since the 1980s - the tests were carried out by Henriette von Prag, an Israeli, who put mice and rats in a cage in which they could follow their natural desire to run. Rats, rodents, run, we see this in the environment, when we see a rat outside that runs away or runs towards us. They are animals that need to move. And, when they were given this opportunity and then tested at an advanced age, to see what their running skills were like, they did extremely well, especially in comparison with their fellows, their siblings, who had only been able to sit still in their cage. So exercise, movement, is one factor, excess weight is another, that has a negative impact on dementia; this we know. That’s why we tell diabetics to get their weight down - it is a factor in the onset of dementia. So this interplay of exercise, social contacts, interaction, and of course an app is wonderful in this regard, but also human contact, dancing groups! We see in the retirement homes, the really good institutions, they activate their patients with music, dancing, cooking together. This is what makes us human, and this is also a factor for treating dementia disorders. This is part of every treatment and will continue to be so.

Friederike Süssig-Jeschor: You have said it yourself. At present this disease cannot be cured. What motivates you then, to go to the laboratory every day and in spite of this take up the battle against this disease?

Professor Dieterich: It is an unsolved puzzle. I am fascinated by puzzles and I am a person who intrinsically likes to make the best of things. I am truly hopelessly trapped by this attraction but also: let us look at the statistics. Every one of us knows somebody with dementia or will have a person with dementia in our close family or group of friends. So it is down to the statistics and also my own family has been affected by it. We watched this exact progression with our father and that is a motivating factor. So it is the attraction of the complex, but also that we really do see, every day, that this disease is increasing, and the figures speak for themselves. As you have already said at the beginning, it is a very, very emotional topic. It can only be tackled with wide-ranging research and that is what we are attempting to do with our research training group. It is what we are trying to do on campus. There is an amazing number of groups that are currently devoted to Alzheimer's disease or dementias in general, and I believe that if we are able to decode a disease of this nature, then we will be able to draw parallels for other neurodegenerative diseases. Perhaps not one-to-one, but still so that we do not always have to start from the very beginning.

Friederike Süssig-Jeschor: You have been working for a very long time on this topic, more than 20 years in this field. Have you ever discovered something that surprised you?

Professor Dieterich: Yes, the interaction of this unbelievably large number of factors: stress, diet, healthy sleep, social behavior, interaction. That was surprising for me. In retrospect you would say, “ah, that wasn’t all that surprising. That was a no-brainer.” But when we stumbled upon the fact that there was a direct connection with diabetes, with a lack of exercise, with an unhealthy diet, that really struck me. And when we looked more closely to see where, for example, around the world, the regions are that are least affected by Alzheimer’s, then it was the regions in which certain foods are consumed more often, like fermented soya beans, spermidine and these have a good effect not only on the brain but on the entire organism.

Friederike Süssig-Jeschor: Let’s come back to the total of thirteen sub-projects. You are the spokesperson, and as spokesperson you coordinate this research partnership. It is an enormous partnership of an amazing number of scientists. You need to find a lot of answers to countless questions all at the same time. How do you manage? How do you get everyone heading in the same direction?

Professor Dieterich: It is like the Wild 13, Jim Button and Luke the Engine Driver - sometimes I feel as though I’m being pulled in fifty different directions at once. How can we succeed? Because we have a common goal and because we have very dedicated sub-project managers, who in some cases already have a long history of conducting research and somehow living together. We have the same goals, of course we have the same defeats sometimes too, but that binds us together. Early on we decided to carry out a long recruitment process for the students who are carrying out research on these sub-projects. This means we organized a small symposium and got to know one another over two days and were then able to search for and find one another from both sides. Research, for me in any case, is always a personal thing. When I supervise somebody, I form a relationship with them. I am responsible for somebody, for training them, and leading them to the next step. So, pointing out career opportunities, but also limitations, that is also part of it. We have extremely dedicated, highly motivated students who also contribute their own ideas, but we have the good fortune that through this recruitment process, so far at least, everything has been extremely harmonious, and we have managed to make the input work with the Wild 13! And input always means having to find a balance. Last but not least, we also have an unbelievably dedicated coordinator, Anika Dirks, who really also brings us all together a bit, organizes joint events, from career events to “The Pint of Science” and that brings us together.

Friederike Süssig-Jeschor: That brings us to the end of interesting discussion about this, in my opinion, extremely important topic. I would like to thank you, Professor Dieterich, for taking the time to speak to us today. Of course I’d also like to wish you continued success in your work and research, and to you out there, thank you for being here.

Intro voice: "Wissen, wann du wilst." The podcast about research at the University of Magdeburg.