Li Juan, a researcher at the Institute of Psychology, Chinese Academy of Sciences.
In fact, in the Nordic countries, the incidence of dementia has begun to decline. Why? It's because in the last 20 or 30 years, the Nordic people have been living healthier and healthier lives. So if from now on, all of you in this room change your lifestyle a little bit, such as eating more regularly, sleeping more regularly, exercising, and eating more nutritiously, then it's very likely that by the time you're old, the incidence of dementia in our country will start to go down as well.
How far is dementia from us
Li Juan
Hello, my name is Li Juan, from the Institute of Psychology, Chinese Academy of Sciences, and the title of my speech today is "How far is dementia from us".
Before answering this question, I would like to ask if any of us here are in the post-50s or post-60s? There seem to be very few, so dementia seems to be far away from all of us. I'd also like to ask another question: how old do people hope to live? I've heard 100, which is very good, and most people have a very good expectation of a long and healthy life.
I estimate that there are about 500 of us here, and I imagine that if we all live to be 60 years old - which should be fine, if nothing else - by the time we get to 60, maybe 20 of us will be demented. Do you know what our average life expectancy is now, 70 to 80? Yes, 76.3 to be exact. So if we all live to an average life expectancy of 76 or 77, the number of people with dementia doubles to 40.
I think everyone here is quite healthy and in good spirits, so it's very likely that we'll live to be 85, and by that time, one in three of us will have dementia. If we're very fortunate to make it to 95, then one out of two of us will have dementia. So if we all live long enough, then there may be only one eventual end, and we all end up in the same place.
Kurz A.,?Eur?J Neurol?1998; 5(Suppl 4): S1-8
Wimo A et al.,?Int J Geriatr Psychiatry?1997; 12: 841-56
Does this sound terrible? It does. Especially as our country enters a period of rapid aging, there are now more than 230 million people over the age of 60 in our country, accounting for 16.7% of the total population. Globally, 22% of the elderly are in China. According to modern research reports on the prevalence of dementia, coupled with our country's dementia underdiagnosis rate of up to 73%, it is estimated that the number of people suffering from Alzheimer's disease in our country has exceeded 10 million, with a new case every 12 seconds.
The burden of disease caused by dementia is nearly 400 billion yuan a year. That's the annual GDP of Kenya, the 70th largest country in the world in terms of GDP.
So let's go back and take a look at what Alzheimer's, or dementia in old age, really is. It was at a scientific conference in November of 1906, and there was a German doctor named Ales Alzheimer who reported a particular case.
German doctor Alers Alzheimer
In 1901, this old woman was brought in by a family member, and by that time she had already suffered from severe memory loss, had great difficulty in communicating with other people, and she suspected her husband of infidelity for no apparent reason. Her condition deteriorated dramatically over the next few years, and in the spring of 1906 she died of a severe infection caused by pneumonia and bedsores.
Dr. Alzheimer had never seen such a strange case before, so he performed an autopsy on the old woman with the consent of her family. He found that the old woman's brain, especially the cerebral cortex, was severely atrophied -- we know that the cerebral cortex is what governs our memory, our speech, our thinking.
And under the microscope, the doctor saw a large number of necrotic nerve cells in her brain, as well as many abnormal protein deposits. People later called the disease Alzheimer's disease, or what we call Alzheimer's, in honor of the German doctor.
The right side of this picture is of a dementia patient. On the outside of the nerve cells in this dementia patient, you can see those black so-called plaques, which are age spots in the brain, but of course they are different from the age spots we usually talk about on the hands or face of older people. On the inside of the nerve cells, there are also tangles of nerve fibers, the so-called tangles, which lead to massive nerve cell death and a reduction in cell-to-cell synaptic connections, which in turn leads to cortical atrophy.
Patient on the right, normal elderly brain on the left
This can lead to a gradual decline in memory and other cognitive functions, as well as affecting mood, personality, and ultimately daily functioning. Dementia is now one of the four major killers affecting the health of the elderly.
In fact, dementia is not always the degenerative Alzheimer's disease, there are about 20% vascular dementia. As the name suggests, vascular dementia is dementia caused by vascular problems. The study also found that roughly 14% of patients had both neurodegenerative Alzheimer's disease and this vascular problem that causes dementia, which is **** disease. There were also roughly 10% with other types of dementia.
This is a self-portrait by an American painter, William Utermohlen. He insisted on painting self-portraits for five years, from 1996 to 2000, after he was diagnosed with dementia. The first is from 1967, when he was still healthy and young.
His self-portrait is a very graphic depiction of the gradual eating away of his brain by this disease. As we can see, the paintings become less and less detailed, and the style of painting becomes more and more abstract, to the point where in the end it may not even be possible to see that this is the face of a human being. And in this process, we may also feel the painter's kind of fear, sadness, is a very heartbreaking process.
These four people are probably no strangers, especially the top two. On the left of the first row is the 40th President of the United States, Mr. Reagan, who was undoubtedly both in a society that relies on both strength and face. The second is British Prime Minister Margaret Thatcher, the "Iron Lady". The third is a Chinese scientist, Mr. Charles Kao, the Nobel Prize-winning physicist who is known as the father of optical fiber. The fourth is Mr. Marquez, the author of "One Hundred Years of Solitude", who is also a Nobel laureate in literature.
So I have been asked more than once: Why are these celebrities also demented? Is it because they work too hard and use their brains too much, causing their nerve cells to die in large numbers and become demented?
While I don't know exactly why they're demented, I do know for sure that they're not demented because they're using their brains too much, causing their brain cells to die. It could be, for example, that they worked too hard, they were under too much stress, they had trouble sleeping and eating, which led to some cardiovascular disease and then dementia. It is said that Margaret Thatcher was induced vascular dementia after several strokes.
In fact, studies have found that those with low education levels and poor lifestyle habits are more likely to suffer from dementia, such as being sedentary and overeating. Then there is a history of severe traumatic brain injury, or long-term exposure to harmful environments, or smoking, which are also more likely to develop dementia. In addition, dementia, like many diseases, is linked to genetics.
When it comes to the genetic link, it may be important to distinguish between two types of dementia: early-onset dementia and what we call late-onset, or senile, dementia.
Early-onset dementia, as the name suggests, is dementia that usually occurs before old age. Currently, there are genes that are responsible for this early-onset dementia, which means that if you carry the gene, then you will usually have dementia before you reach old age. There are currently three causative genes, the amyloid precursor protein gene (APP), progerin 1 (PS1), and progerin 2 (PS2).
People may think, "Do I need to be sequenced to see if I have this gene? You don't have to. If you have more people in your family with dementia, and more importantly, if you have dementia before you reach old age, then it's very likely that you have a family history of the disease-causing genes.
For late-onset dementia, that is, dementia that develops after old age, there is no causative gene. It's not true that if you carry a gene you're going to get dementia when you get older, after age 60, but there is a risk gene. If you carry the risk gene, you are more likely to develop dementia in old age. Probably the most recognized risk gene is the apolipoprotein E gene (APOE).
At this point, you may be interested in the question of what can I do if I get dementia. What is the cure? Unfortunately, there is no cure. In other words, no drug can cure dementia, or reverse the course of the disease, and existing drugs can only partially relieve some of the symptoms. Probably all the drug companies have invested the most in developing dementia drugs, but unfortunately, all of them have failed when they reached phase III.
People may think that the study subjects in phase III are more severely demented, and that it's too late to give them drugs. In fact, the onset of dementia is not sudden in any one person, and the disease is a long process. Now some studies have found that the disease may have occurred slowly for 20 to 30 years before the final clinical diagnosis. So from the time you're in your 30s or 40s, the disease may have started insidiously.
We can look at this graph again, with age in the horizontal coordinate and scores in the vertical coordinate. The cooler colors are some of the cognitive functions, like our episodic memory, executive control functions, and processing speed. These cognitive functions peak in our twenties - probably the age of most of you here - and then they start to decline.
Park & Bischof, 2013?
In addition to these relatively high-level cognitive functions, lower-level cognitive functions such as some sensory perceptions also change as people enter middle and old age. In vision, for example, people perceive colors as warmer and warmer after age 50, and the clarity with which they see objects in motion declines very dramatically after age 60. And research is now finding that a severe early decline in the sense of smell may be an early sign of dementia.
Speaking of hearing, I'd actually like to ask if we have any older people in our homes here who have hearing loss. I can't see it very well from where I'm standing, but I'm guessing it's fairly common. In this case, I would like to ask if we have ever yelled at the elderly because they may not hear us clearly or they may hear us wrongly when they communicate with us because of their hearing loss. We just have to be very honest and recall it in our mind, and I reckon that we certainly have.
In the long run, the elderly may become cautious when communicating with us, and even fearful of socializing with people and interacting with the young. Over time, this may lead to social withdrawal, leading to a reduction in interpersonal interactions, and social withdrawal and reduction in interpersonal interactions are also closely related to the high incidence of dementia.
So, if there is an elderly person with hearing loss in the family, I would suggest that he or she should wear a hearing aid if he or she can get relief from it at the beginning, even though it may be uncomfortable at first. More importantly, of course, we must be patient when communicating with the elderly with hearing loss.
You may remember from the movie clip that the earliest sign of dementia is memory loss like Alice. You may remember that when she was lecturing at university, she couldn't remember very familiar words, and when she was running, she got lost on her regular route.
These are the earliest symptoms of dementia.?
These declines in cognitive functioning can be measured by standardized neuropsychological tests, in addition to the ones you can feel. Here is a clock drawing test, and as you can see, with these three different clocks, we can visualize the gradual progression of the disease.
In addition to these directly observable behavioral changes, there are some early signs that we cannot directly observe, and we need to use other indicators, such as neurological indicators and biological indicators. I'd like to share with you two related pieces of work from my team.
The first one is a neural indicator, which is a result of our collaboration with Prof. Yang Jiang Clark of the University of Kentucky. As you can see in the picture, by putting an electrode cap on an elderly person's head, we can measure the electrical activity in his brain. The old man wearing the cap did a very simple task, actually a memory task, and the results were very interesting.
We had two groups of elderly people, one group of normal elderly people and one group of elderly people with mild cognitive impairment. When they did this memory task, there was no difference in the correctness rate or response time, but if we look at his EEG activity we can see that in the left prefrontal part, the impaired elderly had a significant negative wave. This means that he may have to put in more cognitive effort to achieve the same performance as a normal elderly person.
Li et al.,?Alzheimer's Research & Therapy,?2017
The next example is a biomarker. This one is a study my team did in collaboration with researcher Rongqiao He's team at the Institute of Biophysics, Chinese Academy of Sciences. Formaldehyde, which may be unfamiliar to anyone who has renovated, but you may not know that we actually have formaldehyde in our bodies and metabolize it. Formaldehyde in the body can be measured by collecting morning urine. Our research has found that the higher the level of formaldehyde in an older person's body, the worse his cognitive function will be.
YuJ et al.,?Neuroscience Bulletin,?2014?
So I was talking about how these markers like behavioral markers, neurological markers, including these biochemical markers, can help us find people at what we call high risk for dementia in the future.
What can we do to find those at risk? Or what can we do to help them? You can do physical activity, you can do cognitive activity. Physical activity and social and cognitive activity are two of the most important protective factors, and if you do them regularly, the risk rate for dementia goes down.
Elderly people who regularly engage in daily cognitive activities have a 67% lower risk of developing dementia than those who seldom do these cognitive activities. These daily cognitive activities include playing chess, playing cards, writing in brushstrokes, reading books and newspapers, and even playing mahjong counts.
The Proceedings of the National Academy of Sciences once reported an interesting study in which they scanned the brains of cab drivers in London and found that the volume of the posterior hippocampus in these people's brains was significantly larger than that of controls of the same age. The hippocampus is closely linked to our memories, so that means cognitive activity can change our brains.
Maguire et al.,?PNAS, 2000?
In addition to doing everyday cognitive activities, we can also go to specialized cognitive training, like we usually do in the lab with memory training and executive control. These are the functions that you might remember, the ones that peak in your 20s and then decline, and the main ones are memory and executive control, which is kind of like the CPU in our computers.
When we do memory strategy training, we're going to be teaching some strategies, which are called mnemonics. One of the most classic mnemonic techniques is probably the "palace of memory", or the temple of memory, which is actually positional mnemonics.
According to legend, positional mnemonics was invented by an ancient Greek poet, who is said to have gone to a grand banquet in 447 B.C. Suddenly two young men came looking for him, so he went out. When he went outside, the young men disappeared, the roof of the banquet hall collapsed, and all the people inside were smashed to death, so bloody that there was no way to tell who was who. The Greek poet then relied on his mind to recall the scene of the banquet and who was sitting in the different seats.
After that, the philosophers and politicians of ancient Greece and Rome began to use these so-called memory palaces to help them memorize their speeches. Why? First, because paper was extraordinarily expensive at the time, and writing it down on paper would have been expensive, so he memorized it in his brain. Number two, because it looked cool. It definitely doesn't look cooler when you take a speech and go into a long speech than when you don't take anything at all.
That was a joke, of course. Then someone studied the so-called super-memory people, the strongest brains, and found that 90% of them actually used this mnemonic technique. Scanning the brains of these super-memory people, it was found that during the memorization process, those parts of the brain that govern spatial perception, that is, our parietal lobe, the back of the hippocampus and other parts of the brain are activated more strongly. This also proves that they do use this mnemonic technique.
In time, this kind of mnemonics became more and more used. For example, when we were in the lab, how would we teach older people to use it? When an older person comes to our lab, he passes through a series of classic landmarks, and we have the older person use these landmarks to build a so-called spatial map of the brain, or a memory palace. And then connect the things he wants to memorize with these classic landmarks one by one.
In fact, this memory palace is not so mysterious. The picture shows a memory palace as well, which was supposedly designed by Emma Willard, an American educator in the 19th century. She designed this memory palace at that time in order to teach her students about history. Memory palaces can be big or small, real or imagined by you. But as long as you are familiar enough with it and it is well organized, then it can serve as a memory palace.
It was just said that there is another function called executive control, and we can make a little game to train executive control. It's very simple, later the numbers will appear on the screen, one by one, please remember the last four numbers. For example, 1 2 3 4, what are the last four numbers? 1 2 3 4. If 6 appears again, what are the last four numbers? 2 3 4 6, right.
So here's what we're going to try. I'm going to present it on the screen one number at a time, and your task is to memorize the last four numbers. We'll start now.
--What are the last four numbers? --9 7 2 9
Wow, I realize that there really are a lot of strongest brains sitting among us. It's actually a difficult task, and more than half of us can't remember it when we first start the quiz without daily training, so it's okay if you can't remember it, it just means that maybe you're going to have to start training.
We just said that doing cognitive training is definitely something that can improve or enhance our cognitive functioning, and in addition to cognitive training, physical activity can also. We know that there are a lot of benefits of exercise, and if we do it regularly, you might look like this picture on the right by the time you're 70, otherwise you might be sitting on the left.
But we may not realize that exercise also changes our brains. You may remember the hippocampus as a structure that shrinks at a rate of 1-2 percent per year as we enter old age. There was a study where older people did this aerobic brisk walking, and after a year, it was found that not only did the hippocampus not shrink, but it grew by 2% in the older people who did the aerobic brisk walking. So we're saying that exercise doesn't just strengthen our muscles, it actually strengthens our brains.
Tai chi is one of the jewels of the Oriental culture, and my colleague Dr. Wei Gaoxia's team at the Institute of Psychology of the Chinese Academy of Sciences has found that older people who have been doing tai chi for a long time have a significant increase in the thickness of the cortex in certain areas of the brain, in the areas that are highlighted.
What's even more interesting is the graph below. As you may recall, I said earlier that there are risk genes for dementia in old age, for example, this graph talks about the association with the BDNF (neurotrophic factor) gene.
Erickson et al., 2013
If one carries the risk allele of this gene, obviously, one's memory is going to be worse relative to those who carry the non-risk allele. However, we can see that the two lines overlap in the upper right corner. That is, even though a person carries the risky allele, by exercising regularly, there's really no difference in memory performance between them and those who don't. In other words, exercise counteracts the unfavorable effects that risk genes give us.
Maybe when I said just now that playing mahjong is beneficial, did all the young people here think of playing games? Isn't playing games also good for the health of our brain? Indeed it is. A considerable number of studies have now found that playing games is helpful to our brain health and can prevent dementia. Although there are also a small number of inconsistent studies reported.
Don't these two pictures look so childhood and familiar? The game on the left is the 2D version of Crazy Birds, and the one on the right is the 3D Super Mario, which you should have played at your age. This is an interesting study, actually a recent project, so I thought I'd share it here.
It actually trained two groups of college students, one to play Crazy Birds and one to play Super Mario. Played the game for two weeks, 30 minutes a day. The result was that in the Super Mario group, after two weeks, its spatial memory ability improved significantly.
Spatial memory ability is a very special kind of memory ability. As you may know, in 2014, the winner of the Nobel Prize in Physiology and Medicine was for the discovery that there are location cells responsible for spatial information in the hippocampus of mice.
This 3D Mario is probably because it requires a lot of spatial navigation, and this game is much more stimulating in terms of scenarios. So it would seem that the constant updating of the game is still necessary.
But if we sit there for a long time playing games or mahjong exercise our brain at the same time, may be for our cardiovascular and cerebrovascular circulation will bring adverse effects. However, it does not matter, because the game manufacturers still quite understand the science. We may also have played sports games, we can exercise while playing games, the two can be combined together.
Dance is actually a very good form of exercise, because we can do both physical exercise, at the same time to memorize the movement, memorize the rhythm, can exercise to our brain, especially square dance. There are now 200 million older people in our country, and I suspect that about 100 million of them are square dancing.
In fact, one of the studies we are doing right now is to teach those sedentary seniors to square dance. We're looking forward to seeing if square dancing can help improve the cognitive function of these older people, especially their memory, and if it can remodel their brains, especially the hippocampus.
I just said that the 3D version of Super Mario would help brain health because it's rich in stimulation. But for older people, such games may no longer be suitable. But we can still teach mom and dad and grandparents to play simple video games, or even just teach them to use their smartphones a bit.
For the elderly, especially those who are senior citizens, over 75 years old, if he learns to use his smartphone, for example, if he learns to use WeChat, and he is able to set up a group with his old friends, colleagues and classmates from the past, and he can share bits and pieces of his life in his circle of friends, it is actually tantamount to opening up a very interesting door to his life.
These pages next to it may not be very clear, in fact, this is a netizen in order to teach mothers and fathers how to use WeChat to do the guidebook, illustrated with text, really let a person very touched.
In fact, looking back, many of us here may have started out very well when we taught our moms and dads how to use smartphones, and we may have been impatient for a while. But let's think about it, did mom and dad ever get impatient when they were trying to teach us how to use a spoon?
Maybe some of our friends have noticed without realizing it that mom and dad are no longer the same people who were very upright and able to take care of everything for us. Sometimes we suddenly realize how they have become careful in front of us and sometimes timid like children. Because they are getting old, they actually need our care, our love.
Many young parents say they want to be involved in every step of their children's development, but ask yourself, are we actually missing out on a lot of opportunities to be involved in the second half of an older person's growth or development? In fact, teaching older people to use electronic devices is a great opportunity to feed back, on the one hand, it can exercise their brains, on the other hand, it can also broaden their social network. This is actually good for preventing depression and loneliness, which are common negative emotions in old age.
So to summarize what we just said, it's good to do exercise, and it's also good to do more educational activities. And we wondered curiously if those two together would be even more beneficial. There's an interesting animal study that answers that question.
The animal is actually a rat. On this picture, on the left are four feeding conditions, the top one is the usual feeding condition, the second one has a lot of toys in the usual feeding condition that the rats can play with, what we call an enriched stimulating environment. The third condition also has a big roller in which the rats can also exercise. The last one, which was a combination of the first three, had both toys and a big roller.
How did it turn out? You can see that the right side is actually a sub-structure of the hippocampus, called the dentate gyrus, which is more posterior to the hippocampus. The hippocampus is actually not that big, unilateral hippocampus is about five or six cubic centimeters in size. The red dots in the dentate gyrus are newborn nerve cells.
Kobilo et al.,?Learning & Memory?2011
We can see that under the conditions where there is wheel movement, there are a lot of red dots in the dentate gyrus, which means there are newborn nerve cells. There are probably only two places in our brain where nerve cells can be born, the dentate gyrus and our olfactory bulb.
But the second condition is that no nerve cells can actually be born if there is only abundant stimulation. So let's look at this last combined group of conditions. It actually looks like there are more red dots, because although enrichment stimulation doesn't lead to neuronal neogenesis, it does lead to better maintenance of the existing function of the neuronal cells and slower apoptosis. So the last condition looks like it has the most nerve cells in it.
This animal study actually inspired my group to do a study with humans as subjects. We selected four neighborhoods in Beijing's Chaoyang District, on the street of Olympic Village, next to our office, and invited some elderly people from each neighborhood to participate in our study, randomly assigning the elderly people in these four neighborhoods to four conditions.
One was the control group, which did nothing. One was told to do cognitive training. Another one did tai chi in addition to cognitive training. The last one is the comprehensive intervention group, where we do psychosocial counseling on top of the first three.
We can see the results. Cognitive ability and social functioning were the most improved in the comprehensive group. And after three months we did follow-up and found that these effects were still retained. There's no way to see nerve cell renewal directly in people, but we can use noninvasive neuroimaging techniques, such as MR*** vibration, to scan the brains of seniors before and after the intervention.
As a result, we found that functional connectivity between the hippocampus and the prefrontal lobe, the two regions most closely associated with memory and executive control, and the ones most affected by aging, improved significantly after training.
And even more interesting is the bar graph below. The vertical coordinate of the bar graph is how similar the brains of older people are to the brains of younger people, with the pink bar representing older people after our training and the blue being untrained. We can see that the brain of the elderly after training is becoming more and more similar to the brain of the young in all the five brain networks below. In other words, older people are becoming more and more like younger people.
I think all of us who are over 30 probably have the same ****: we want to be younger. Don't you all want to? So from here doesn't it feel like a dream realized too suddenly. You do the training, your brain is able to become younger, it looks more like young people.
In addition to cognitive training and exercise, comprehensive interventions can also include nutritional diets. And a very important point is the control of cardiovascular disease risk factors.
Currently, the cutting edge and hotspot of research in this field is to take these risk factors and protective factors into account to make comprehensive interventions. One such research program that has the largest sample size in the world and has reported positive results is the FINGER program. It's actually an acronym for the Finnish Dementia Prevention Program, and the F is actually for Finnish. That's because the program originally started in Finland, even though the leader of this study was based in Karolinska, Sweden.
Now we can see that globally, the United States, the United Kingdom, Australia, China, Singapore, a whole range of countries actually have research programs and research projects that use similar research protocols. My group is also a member of CHINA-FINGER.
We are actually working hard on this path right now with scientists in various parts of the world. Even though we don't know exactly how dementia develops, it doesn't prevent us from making comprehensive interventions to address the risk factors and protective factors that we do know. I especially hope that interested young people here will join our team.
We say that population aging is a global challenge that cannot be reversed, but it does not necessarily follow that the incidence of dementia will increase with population aging. In fact, in the Nordic countries, the incidence of dementia has already begun to decline. Why? It's because the Nordic people have been living healthier and healthier lives over the past 20 or 30 years.
So if we change our lifestyles a little bit from now on, such as eating more regularly, sleeping more regularly, exercising more regularly, eating more nutritiously, it's very likely that by the time you're old, the incidence of dementia in our country will have begun to fall.
Lastly I'd like to share a couple of interesting findings that have been published recently. The first is a team of researchers at MIT who developed a functional drink that nourishes synapses.
Why don't you go to heaven.