Can playing brain games delay and prevent Alzheimer's disease? | World Alzheimer's Day

Today (September 21) is World Alzheimer's Day and this year's theme is "Let's Talk About Dementia".

In today's world, dementia affects families as widely as cancer. Countries with aging populations and low birth rates are on the verge of a major outbreak. Is there any way to delay and prevent it early?

British neuroscientist Joseph Jebelli has been committed to studying Alzheimer's disease for a long time and has conducted a lot of field research and interviews. In Chapter 12 of his new book, Chasing Memory: Fighting Alzheimer's Disease (China Science and Technology Press, June 2020), the author strives to answer the very practical question of whether brain exercise can help fight Alzheimer's disease. At the same time, he also describes to readers the selfless pursuit of a Japanese doctor (see below 2 for details).

This book contains both gripping scientific research stories and the surprising inside stories behind the headlines. On February 17, 2018, in an interview with CBS, Dr. Jebeli said: The real cure for Alzheimer's disease is to reverse the diagnosis and treatment earlier. In addition, he also shared with readers the inspiration and insights brought by research in Iceland, India and other places (see below for the transcript 1, and click https://mp.weixin.qq.com/s/xGaMY1jnsAYiBz2XIQTezg for the interview video).

Q: What inspired you to embark on your personal research journey?

A: My interest in Alzheimer's disease stems from my grandfather's experience with the disease. When I was a teenager, he was going through Alzheimer's disease. Like many people, I wanted to know what was going on, what this disease was, what happened to my grandfather, and how we could stop it, and that's how I got interested in this field. I then decided to write this book to provide the public with a report on the evaluability of our research in this field, the history of the research, the means to achieve the ends, and where it's going in the future.

Q: Alzheimer's disease is expected to overtake cancer as the world's second leading cause of death by 2050, affecting millions of people worldwide. So what is the difference between Alzheimer's disease and dementia?

A: “Dementia” describes the cluster of symptoms you see in people with Alzheimer’s, such as memory loss, disorientation, confusion, problems with general thinking skills. But Alzheimer’s describes the underlying disease process of dementia. So to say someone has dementia is like saying they have cancer without identifying what type of cancer they have. So Alzheimer’s is just one type of dementia, just like there are different types of cancer.

Q: You trace the origins and history of Alzheimer's disease. How much do you think public attitudes toward Alzheimer's disease have changed over the years?

A: It's changed a lot. The data in the book show that we have basically moved from fear and apathy to understanding and hope. When German psychiatrist Dr. Eros Alzheimer described the disease in 1906, it was mostly ignored by his peers. The idea of ​​linking biological representations of the brain to behavioral manifestations was a foreign concept at the time, although it is no longer so it took a long time for researchers to finally realize the problem. In the 60s and 70s, Alzheimer's disease was rediscovered by some amazing psychiatrists, such as Martin Ross, a Hungarian, and Michael Kidd, an English microscopist. Since then, people have really awakened to Alzheimer's disease and began to understand it as a disease process that we should treat scientifically and rationally, just like cancer.

Q: When you talk about early warning science, you give the example of people panicking when they misplace their keys, and then you argue that we shouldn't be alarmed by that behavior, but rather take it seriously when we can't remember what our keys were for.

A: Exactly. It is normal to forget where your car keys or glasses are. As we age, we forget things every day. You may not be trying hard or you may be a little tired. When you see your keys and glasses and suddenly ask yourself "what are these?", it indicates something more sinister and that you should really pay attention and see a doctor.

Q: And loss of mobility is also an early sign.

A: Yes, disorientation. There was some excellent research last year showing that it is actually one of the earliest signs, and it may even precede memory loss. Disorientation may be one of the earliest signs.

Q: You talked about how we move from fear to hope. How close are we to a technological breakthrough?

A: The most optimistic estimate, which I, a natural optimist, agree with, is that within 10 to 20 years, we will have a breakthrough in at least one effective treatment, because what we really need to do is to push the age of disease discovery forward. The treatment for Alzheimer's disease is actually not what many people think. The real treatment is to push back, to diagnose and treat earlier. If we can diagnose and treat one year earlier, there will be 9 million fewer cases by 2030. If we can diagnose and treat it five years earlier, the 46 million Alzheimer's patients worldwide will be reduced by half. So we just need to push it back and change the course of the disease so that the victims never experience the symptoms of these diseases.

Q: Yeah, and going backwards means that patients no longer die from Alzheimer’s disease.

A: Yes, you can die naturally. You won't have to go through these devastating processes in your final years.

Q: How can we achieve this backwards? Vaccine? Repair? Treatment? A chronic treatment like curing a diabetic patient?

A: Yes, it will become increasingly necessary to treat it early. We know that Alzheimer's disease is a decades-long disease process, and it actually takes 10 or even 20 years to see symptoms, so now scientists are looking for early markers, such as cerebrospinal fluid, blood, and even eyes, and trying to detect the disease in middle age and reduce the risk of disease later in life, so as to completely derail the disease process.

Q: You went to Iceland, Colombia, and India for your research. What did you do specifically?

A: Yes, I did travel a lot to write this book. I fundamentally realized that as a scientist, you really should leave no stone unturned. Who would have thought that there was a group of people in Iceland who were genetically immune to Alzheimer's disease, who would have thought that there were some farming communities in India whose lifestyle protected them from Alzheimer's disease, who would have thought that there were some Colombian patients who had already studied Alzheimer's disease and revealed its causes. So we really need to expand our research on how to cure this disease, because it is a more complex disease than we previously thought. That's what I look for as a scientist. We should search widely.

Q: This is a fascinating book, Chasing Memory: Fighting Alzheimer’s Disease. Thank you, Dr. Gabelli, for sharing this.

A: Thank you.

Can playing games delay and prevent Alzheimer's disease? Everyone will appreciate and admire fruitful research. The difficulty of research is to keep working hard when the results are unclear and the reasons are unclear.

——Still Alice (Lisa Genova)

Written by Joseph Jebelli

Translations | Qi Zhongxia, Zeng Hui

Ryuta Kawashima, a 41-year-old Japanese doctor, began studying the effects of video games on the brain in 2001. Kawashima, who previously conducted neuroscience research at the Karolinska Institute in Sweden and now works at Tohoku University in Japan, knew from the start that functional brain imaging was his passion. The temptation to see the changes in mental activity translated into instantaneous brain images on a screen was irresistible. Functional brain imaging is a living mirror map of the brain, where the observer's various reactions to the outside world are reflected in the brain functional image like an image in a mirror. Two years later, Kawashima published a book full of strange cartoon characters performing various daily behaviors and corresponding brain functional imaging maps next to them. The book also includes simple mental arithmetic, various puzzles and quizzes. As the book clearly states, these contents are designed to "help rejuvenate the brain and improve brain function to a higher level." Kawashima's dream was to turn brain health care into a "social welfare" cause. In 2005, it can be said that his dream came true. The famous Japanese game company Nintendo released the video game "Brain Exercise" developed by him, which set off a global gaming craze.

I've never been very good at Kawashima's famous game. I was a little surprised to hear that playing these games can prevent Alzheimer's disease. I don't think people even agree that playing video games can help your health, let alone prevent or cure diseases. But believe it or not, for more than a decade, thousands of nursing homes across Japan have been using these games as a means of preventing Alzheimer's disease, which is actually a last resort.

A quick look at Japan's demographics shows why. The East Asian island nation now has the world's oldest population, with nearly a third of its population over 65 and 40 percent expected to do so by 2055. During that time, the country's population is expected to drop from 127 million to 90 million, thanks to its notoriously low birth rate. Meanwhile, Japan is on the brink of a massive outbreak of dementia. Given the severity of the situation, Japan's health minister has called for an additional 1 million foreign nurses and elderly care workers by 2025.

So, does playing that game really help your brain? Kawashima thinks it does. "I believe that the brain is still the same whether it is a child or an old person," he says, sitting across from me in Kawashima's office at Tohoku University in Sendai, northern Japan. I'm so intrigued by the idea of ​​using computer games to treat Alzheimer's that I can't miss the opportunity to meet him face to face. "I know that brain function naturally declines with aging, but I think that through 'brain exercise', cognitive function can be maintained to at least a certain extent." "Will it work for Alzheimer's patients?" I ask. "Of course!" Kawashima replies, almost surprised that I've asked the question. He tells me that more than 30,000 people are using the game, and it's working very well in nursing homes. "In fact, people often invite me to visit those nursing homes. They say that games have brought incredible changes. I didn't believe it at first. It didn't seem real, just random talk. But then I went to the nursing home and realized it was true. Some patients used to do nothing but sleep and sit in wheelchairs when they were awake. Now they can even do some simple arithmetic."

I couldn't help but be moved by Kawashima. He was dressed in a long black suit, neat and capable, and looked 20 years younger than his actual age of 62. Kawashima was calm and gentle, and I soon realized that behind his calm attitude was his absolute confidence. Although his game invention attracted many doubts, some colleagues even called him a "liar". These views did not change his original intention at all. He was not trying to cure Alzheimer's disease with games, but just trying new methods, different methods. These methods may really work and can slightly delay the deterioration of patients' conditions.

What attracted me most in Kawashima's office was his bookshelf, where books and Nintendo DS games took up about half of the space. He took down a game to show me. "This is Nintendo's 'Concentration Training' game, which is super difficult. In Japan, it is also called 'Devil Training'." He also pointed to a photo on the cover, a cartoon of Kawashima's own head. "Look, I've become a devil!" He laughed and said loudly.

"It's true that it's a bit too difficult for people who have already developed dementia. I'm more interested in how to prevent dementia. You know, after the age of 40 or 50, beta-amyloid and tau proteins start to accumulate in the brain, so I believe we must regularly exercise our brains before the age of 40."

Before meeting Kawashima, I did some serious research on the scientific basis for so-called cognitive training. Some researchers believe that the positive effects come from the Hawthorne effect or the so-called observer effect, that is, when people know they are being observed, they will change their behavior. For example, test takers may improve their test scores by silently reciting some required questions in their minds, but this does not mean that their cognitive abilities have actually improved. Other researchers believe that the brain is always plastic throughout a person's life, but we have not yet developed the right tools to study the impact of daily activities on the brain.

In September 2009, the Alzheimer's Society of the United Kingdom funded a large-scale trial involving more than 13,000 people. The trial found that cognitive training had no significant effect on people under 50, but for people over 60, five 10-minute sessions a day for six months helped them complete daily activities. These daily activities include shopping, remembering things to do, and managing household finances. The researchers claim that the improvement can last up to 5 years. For human brains in their 70s, the experiment showed that cognitive training can increase blood flow in the prefrontal cortex and strengthen neural connections between the two hemispheres of the brain. The frontal cortex is so closely linked to human thinking that some researchers have even called it the "organ that breeds human civilization." Can cognitive training really prevent Alzheimer's disease? The answer is that we don't know yet. Some studies suggest that it may work. For example, a research team in the United States spent five years surveying 700 people over the age of 65 and published their findings in 2012. They found that people who regularly did crossword puzzles or jigsaw puzzles, or played board games, had a 47% lower risk of developing Alzheimer's disease, but the study was small and the authenticity of the findings has been questioned by many.

We can also consider the following passage written by cognitive neuropsychologist André Aleman in 2014: “Cognitive training exercises brain abilities, including memory, attention, and thinking… which tend to be very specific, whereas the decline in brain function in Alzheimer’s disease is global. If people do a lot of Sudoku puzzles, they will become good at Sudoku, but other aspects of the brain will not necessarily be exercised or sharpened.”

Kawashima stressed that while the research behind "brain training" games is still in its early stages, he is convinced that these games can have a huge impact on the brain. "We know that brain activity training can activate the prefrontal cortex," he said, "and the prefrontal cortex plays a key role in higher-level cognitive functions, such as memory, attention and decision-making. If we can stimulate the prefrontal cortex in a way, its basic functions will be improved. Of course, this is just my guess."

I thought the idea sounded plausible enough to make me pull out my old game console and start spending some time training my brain before I turned 40. Japan is a mecca for video gamers, and I felt that "brain training" was not just about fun games, but also about a purposeful and innovative technology industry. In fact, Kawashima is trying to dissect the neurological effects of games using neurofeedback experiments, where a person can watch their brain activity on a computer screen while playing a game, and can control specific brain activity patterns by focusing on different aspects of the game. It makes sense that Nintendo will continue to pay close attention to Kawashima's research. Kawashima is not a boaster. He once refused to sell his invention, even when the other party offered him 15 million euros. Similarly, he did not keep the $30 million in patent royalties for himself. "My wife is very upset with me because of this," he said to me with a grin. "Why would you refuse such a large income?" I found it hard to believe.

He shrugged and said: "I don't think the money belongs to me. I'm just a staff member of the university, doing my research. My salary is paid by Japanese taxpayers, so I think the money should belong to the university."

Kawashima uses the proceeds from game development for his research at Tohoku University. Shin and Akira are two of a group of energetic 40-something neuroscientists who lead him around. They take me to a lab in a building across from Kawashima's office. The lab is painted white and mice are doing "brain exercises." They're not playing games. They've designed a clever simulation. First, the mice live in a bare cage with almost nothing to excite their brains. Then they're moved to an "enriched" cage filled with toys, passages, steps, and mazes. Akira changes the maze three times a week to keep the mice fresh. Then Akira uses a specialized mini MRI machine to observe changes in their brains. "I'm looking for evidence of plasticity in the mouse brain," he says, "changes in the structure of the brain and the connections between different parts." Surprisingly, every time Akira trained the mice with an enriched and interesting environment, their brains grew in size. Crucially, the changes occurred in both old mice and mice genetically modified to have Alzheimer's disease.

Qiu Liang believes that this situation may be related to another theory called "brain reserve". This theory was proposed by James Mortimer, an American gerontology researcher. He believes that every brain has the ability to resist intellectual decline. This ability has nothing to do with structural damage, but depends on the amount of benign mental stimulation people receive in their lives. The more benign stimulation people receive, the greater the brain's ability to resist adversity. He believes this is why some people do not develop dementia even though they have plaque accumulation in their brains.

In 1990, Mortimer and epidemiologist David Snowden studied the “brain reserve” of a group of elderly nuns. These highly educated nuns lived in the Sisters of Notre Dame in Mankato, Minnesota. Snowden thought they were ideal candidates for an experiment. Their well-organized schedules, diet, and exercise regimens helped to eliminate random factors and focus the study on the role of education. The nuns kept meticulous records of their lives, which meant Snowden had access to medical and historical records dating back to the late 19th century. These records included a collection of autobiographical writings that the nuns had written when they first entered the convent in their 20s. By analyzing the grammatical and semantic complexity of these writings, Snowden found that the complexity of the writings, which he named “idea density,” was strongly associated with Alzheimer’s risk.

For example, describing siblings, one nun wrote: "There are 10 children in the family, 6 boys and 4 girls. Two of the boys are dead." Another nun wrote: "The family started with one boy and one girl, two children, and gradually grew to 8... When I was in the fourth grade, death came to my family and took away my most beloved brother, Carl. He was only one and a half years old at the time." Of the two nuns, the first one would be more likely to suffer from Alzheimer's disease.

Almost unbelievably, 90% of the nuns with lower "thought density" later developed Alzheimer's disease. Based solely on these articles written more than 60 years ago, Snowden could predict which nuns would become ill with an accuracy rate of 80%.

The surprising findings of the "Nun Study" caused a sensation as soon as they were published, and media outlets of all sizes competed to report on it. Time magazine even put a nun on its cover with an alluring headline: "Believe it or not, this 91-year-old nun can help you beat Alzheimer's disease." As Snowden wrote in his book Aging with Grace:

We now know that the brain is always capable of changing and growing. Of course, most of the brain growth occurs in our first years of life… Parents ask me whether they should play Mozart to their children, buy expensive educational toys, ban television, or start using computers early. I give them the same answer… “Read to your children.” If “brain reserve” is real, it should be a developmental phenomenon that provides lifelong protection for the nervous system.

In Kawashima's view, it's never too late to continue exercising your brain in adulthood. With the number of people with Alzheimer's growing rapidly in Japan, Kawashima's mission is more urgent than ever. "My ideal is to successfully prevent this disease," he said when I said goodbye to him. "That's also my hope and my dream."

This article is authorized by the publisher and excerpted from Chapter 12 of "In Search of Memory: Fighting Alzheimer's Disease". The original title is "Brain Training".

About the author: Joseph Jebelli is a British neuroscientist and popular science writer. He graduated from the University of London with a PhD in neurobiology. The author has been engaged in the research of Alzheimer's disease for many years and is trying to find a way to use the body's immune system to stop the progression of this disease. He has done relatively new research in this field. The author has written articles for the British "Guardian" and "Wellcome Trust" and is a scientist who loves popular science creation.