 I am a neuroscientist at the University of Munich. It is a pleasure to be here to talk about a topic that is very close to my heart. And this topic is one of the reasons why I get up every morning and work as a neuroscientist for the past four years. But before I dive into the topic of cognitive reserve, I would like to ask a favor. So I will give you three words. Please try to remember these three words. Don't write it down, simply try to remember. The first word is spoon. Second word, clock. Third word, hospital. So three words, simple enough. Spoon, clock, hospital. Are we good? Everybody gets the word? Okay, good. So let's begin with the good news. Most of us will be lucky enough to be able to celebrate our 70th birthday with family and loved ones. Why? This is because the average life expectancy according to the World Health Organization is 71.4 years. Yes, compared to older generations, we have so much more time to enjoy what life can offer. The bad news is, with as we age, we have higher rates of developing degenerative diseases such as those affecting memory. According to the World Alzheimer's Report, every three seconds someone in this planet develops dementia. 70 to 80% of those dementia are caused by a disease called Alzheimer's disease. Even after 100 years of discovery of Alzheimer's disease, there is still no cure for AD or Alzheimer's disease. Five drugs are approved by the FBA to slow down the symptoms of the disease, but not to treat or cure it. So with this information in mind, I would like to bring your attention to my topic today. First, I will describe what happened to the brain when Alzheimer's disease strikes. And then I will introduce and explain the concept of cognitive reserve. And lastly, we will take a look at some factors that are associated with high cognitive reserve. So let's begin with what happened to the brain when Alzheimer's disease strikes. This is a picture of a healthy, normal human brain. Alzheimer's disease caused nerve cell death as well as tissue loss. As a result, the brain shrinks dramatically. This damage caused progressive problems with memory, thinking, or behavior, which means that the problems get worse and worse and worse over time. At the early stage of the disease, the damage usually happened in areas involving memory, such as the hippocampus or the orbital frontal cortex. At this stage, though, no symptoms can be detected. If there are symptoms, usually it's comparable to normal aging. At the moderate stage, the damage is spread out, and at this stage usually there is a mild memory loss, difficulty remembering new information. As the brain gets more and more damaged, then the damage or the tissue loss spreads almost throughout the entire area of the brain. As a result, at this stage, usually patients with Alzheimer's disease experience confusion, mood changes, not being able to recognize family members. And of course, when this happens, patients with advanced stage of Alzheimer's disease they cannot take care of themselves, so they cannot live independently. The diagnosis of Alzheimer's usually happens in these two stages, and life expectancy of the diagnosis varies between four to eight years. With this information in mind, Alzheimer's disease is affecting a lot of people, and there is no cure. But is there any hope if we can actually slow down the progressions of the disease? A glimpse of hope actually came in 1988 when a group of researchers did a post mortem study. So what they did is that they took brain specimens for the people after they died. So they took 137 brain specimens from residents of nursing or senior home. And the good thing about this study is that throughout the life of the people who donate their brain to science, their memory functions and other cognitive functions were monitored because they live in a nursing or senior home. So they were tested for the memory and cognitive function. To their surprise, ten brain specimens, so ten residents of the seniors or nursing home had quite an advanced stage of Alzheimer's disease. So from the brain specimen itself, it looks like the brain is affected by this damage. However, they did not exhibit any symptoms of Alzheimer's disease. So the brain actually coped up with this damage and they could function as normally as possible. At that time, they didn't understand why did this happen? What is it? But after that period, after 1988, neuroscientists start getting interested in this concept that we know now as cognitive reserve. So what did they actually look at? What this cognitive reserve all about? Well, to put it in a simple term, it is a discrepancy or a mismatch between brain damage and cognitive function, or between pathology and cognitive function. To illustrate this concept or this phenomena even further, I would try to use this graph. So this graph is not very complicated, but let's dissect it one by one. So let's begin with these axes here that represent the severity of brain damage from mild to advanced. And the severity of brain damage is usually monitored, used for example this imaging technique, the magnetic resonance imaging, that can take an anatomical picture of our brain and then from this picture we can see or we can measure how much damage or how much shrinkage is experienced by the brain. So we can measure certain areas of the brain, the volume of certain areas of the brain. So then we can classify the brain damage from mild to severe. Let's add another axis. These axes represent cognitive function from normal cognitive functions to severe impairment. How do we measure this cognitive function? One way is what I call what is called as word recall test. In the beginning of the presentation, I gave you three words. Now it's your time to prove to me that you're all healthy. So what are those three words? Spoon. Very good. So you're all covered. So that's a word recall test. Usually the physician gave three words and in a time that the patient or the subject did not expect, oh I just gave you three words in the beginning, what are those? They are. So this word recall test or other way is the mini mental state examinations or the Montreal cognitive assessment. Using these test batteries or using this test, we can classify the cognitive functions from normal to severe impairment. So now let's talk about two axes and what happens when there is no discrepancy between pathology and cognitive functions. So there's no mismatch. So what happens is when the severity is mild, then the cognitive functions appear normal until certain times that the damage become more severe then the cognitive function starts declining rapidly. So this is what we observe in Alzheimer's dissertation. In some individuals, though, there is a discrepancy. So even until moderate damage of the grave, the cognitive function still appear normal only when the damage become more and more advanced, more and more severe then the cognitive function starts declining. So why is this important? Well, the diagnosis of AD usually happens here. So as you can see that once people is diagnosed, the cognitive functions decline rapidly and for these individuals that doesn't have high cognitive reserve, these blue lines here, they have to suffer longer with the consequences of the disease. While those with the high cognitive reserve like this one, the times from the cognitive decline until they die is usually shorter. So then they don't have to suffer the consequence of this cognitive decline as long as those with the low cognitive reserve. So now, are there any factors associated with the high cognitive reserve? Are there any way we can make our brain more resilient to damage? The answer is yes and that's why I'm here today. So first factor is level of education. So this is an example of a study involving 1,563 participants and in this study, the researcher classified participants into three different groups. Based on their level of education, what is 12 years or less, so primary and secondary school? 13 to 16, so those who experience tertiary education including two year college or the bachelor degree for example and 17 or more. So those who take it all the way from primary school to PhD for example or maybe get a second PhD. Maybe you have time. So now we have the graph again. So they categorized the damage into three different categories, so moderate and severe. And then they looked at, for each of these groups of individuals based on their level of education, how many are close, showing symptoms of Alzheimer's disease. And let's look at the low level of brain damage. And what they found is that the more educated, the higher level of education, the lower risk of Alzheimer's disease this group has. And as you can see here, only 25% of those with 17 or more years of education actually exhibit symptoms of Alzheimer's disease with the same severity of brain damage. And this trend also continues with the moderate as well as the severe. The second factor is complexity of jobs, so your occupation at the moment. There are several ways to determine how complex your jobs are. Two factors, one is numbers or data and the second one is people. So jobs with low complexity of data or numbers would be, for example, a cashier. And moderate level of complexity would be like an accountant or highest one, maybe like a theoretical physicist. Well, that's the only thing I can think of at the moment. With as high as possible. So with people, for example, low complexity in terms of people would be like a barrister. Moderate would be like a news anchor. Highest, I can think of like a hostage negotiator. So as you can see from this example, these are not just categories. It's more like a fluid scale, of course. From this example, as you can see, it doesn't really matter how many data or people you deal with, but it's more the level of engagement. For example, a barrister might deal with more people on a daily basis than a hostage negotiator, but the level of engagement of a hostage negotiator is more complex because maybe they have to analyze people, persuade people, negotiate with people, or sometimes manipulate people. And what the researcher found out is that with increasing complexity there is better chance for higher cognitive reserves. So increasing complexity of the job is associated with higher cognitive reserves. Last but not least, physical activities. So from these activities, golf, biking, running, gardening, tennis, dancing which one do you think promotes cognitive reserves more? Dancing. Yes, that's correct. So they found that for those who regularly do dancing when they're young, they exhibit less risk or less symptoms of dementia and Alzheimer's disease. Well, I've told you about what happened to the brain when Alzheimer's disease strikes and we know that there's no cure, but there are hopes because of the concept of this phenomenon of cognitive reserve. And we as neuroscientists, we still try to understand the brain even more. We still try to find the best way to treat certain brain diseases. But we can't do it alone. We need your help. And one way that you can help is, for example, we always look for participants. We always want to see what's inside your head. We always want to take pictures of your brain. So if you're interested or there's someone who is interested, you can contact me. There are lots of different studies that you can take part of. Now I'm doing studies with older people. So if you know anyone, and you can get up to 100 euro as the gift from us and many other projects, of course. Or if you are interested in cognitive reserve, next week there is a conference on cognitive reserve only because this is such a fascinating subject for us neuroscientists at the Institute for Stroke and Dementia in Munich. So, well, with that, I would like to conclude my presentation with a salute that I think is very fitting for talk on aging and cognitive reserve. So I wish you all to live long and prosper. Thank you very much. You gave a bunch of examples with, say, like higher education correlating positively to the higher levels of cognitive reserve. Is that correlation only or can you prove causation? Is it maybe just something inherent in the people who were perhaps born with the genetics to predispose that? Yes. Thank you for the questions. That's an interesting question because, of course, with this study we cannot explain causation. We can only see correlation because if we want to look at causation then we have to take 200 group of participants, divide them into two and in one of them we have to say you cannot educate yourself whatsoever. And in the other group we say we will educate you as high education as possible. So no ethics committee will allow us to do that, fortunately. We would like to do it. Fortunately. And the other thing that people also look at when you talk about if it is a genetic factor, there has been studies on that as well but the one that is very robust and always come out as a positive association with cognitive reserve is the level of education. One way is because the more you train your brain the more likely the brain can actually compensate for damage. And second of all, high level of education is quite easy to quantify compared to others. Some studies have tried for example IQ level but the problems with IQ is that you can't actually test the IQ on the people who already have the damage brain, for example. So it's a little bit harder to establish the correlation. I hope that answers your question. So you said that the people that hire cognitive reserve they show signs of Alzheimer's. But the damage to their brain is the same. Yes, the damage to their brain is the same. They won't realize that they have Alzheimer's and the damage is too much. Do they have it bad? That's a good question. Because the thing is what now scientists are trying to look at is that we cannot cure or treat Alzheimer's or treat the root cause of it but can we do something so that as we age we can age more gracefully. So in a way that, okay, now instead of suffering for eight years well we kind of limit your suffering to two years. So then six years you have a good life with your family and then usually those who, because in the end they die but before they die they still have the ability to remember their family members. And I think this is something that people want to have as well. We have time for one question more. I don't have the number in mind unfortunately. But these are the drugs that are proved to slow down. But then again, usually when the patients are already treated with this drug the progressions of the decline in cognitive function is already quite severe. Because you don't diagnose Alzheimer's disease when... Yeah, some problems. Okay, so you don't diagnose people with Alzheimer's disease when they are still healthy and can't remember stuff. But usually it's when they start confusing like okay or taking Christmas decorations in March for example then you start the diagnosis. Yes, so that's also one of the reasons. I'm a neuroscientist myself and every six months I get a brain scan. I participate in a study and then I get a brain scan. That is like the way that you can actually do to actually see if there is something wrong with your brain as early as possible. Not that I'm promoting my study but yeah. I think it was a great talk.