|
演说者：Lisa Genova 演说题目：我们如何预防老年痴呆症？ 神经科学家同时也是《我想念我自己》的作者Lisa 说，「老年痴呆症不一定是你大脑的宿命」。她向我们分享这个疾病最新的科学调查，以及一些前瞻性的研究，让我们可以做些事来建构起 一颗「对抗老年痴呆症的大脑」。 中英对照演讲稿 How many people here would like to live to be at least 80 years old? Yeah. I think we all have this hopeful expectation of living into old age. Let's project out into the future, to your future 'you's,' and let's imagine that we're all 85. Now, everyone look at two people. One of you probably has Alzheimer's disease. 在座有多少人希望能活到八十岁以上？ 好。 我想我们每个人 都渴望能够长寿。 让我们穿越到未来， 未来的你们 假设都已85岁。 我们随便挑选两个人， 其中一人就可能患有老年痴呆症。 Alright, alright. And maybe you're thinking, 'Well, it won't be me.' Then, OK. You are a caregiver. So --so in some way, this terrifying disease is likely to affect us all. 好吧，好吧。 也许你会想：“反正不会是我”。 那么好的。你是另一位的照顾人。 所以……所以某种意义上来说， 这个可怕的疾病可能 会影响我们每一个人。 Part of the fear around Alzheimer's stems from the sense that there's nothing we can do about it. Despite decades of research, we still have no disease-modifying treatment and no cure. So if we're lucky enough to live long enough, Alzheimer's appears to be our brain's destiny. 对于老年痴呆的恐惧部分源于 我们对此的无能为力。 尽管几十年的研究下来， 我们依然没有改善病情的方法。 如果我们有幸长命百岁， 老年痴呆似乎是我们大脑的宿命。 But maybe it doesn't have to be. What if I told you we could change these statistics, literally change our brain's destiny, without relying on a cure or advancements in medicine? 情况也许没有这么糟。 如果我告诉你，我们可以改变现状， 就是改变我们大脑的命运， 不依赖于任何疗法或是药物的发展呢？ Let's begin by looking at what we currently understand about the neuroscience of Alzheimer's. Here's a picture of two neurons connecting. The point of connection, this space circled in red, is called the synapse. The synapse is where neurotransmitters are released. This is where signals are transmitted, where communication happens. This is where we think, feel, see, hear, desire ... and remember. And the synapse is where Alzheimer's happens. 让我们先看看目前 神经学上对老年痴呆的了解。 这是一张两个神经元连接的图。 连接的部位，也就是红色圈出的这块， 叫做突触。 突触是神经递质释放的场所， 这是信号传送、交流的场所。 这是我们思考、感受、视听、欲望 和记忆的场所。 而突触也正是老年痴呆发病的地方。 Let's zoom in on the synapse and look at a cartoon representation of what's going on. During the business of communicating information, in addition to releasing neurotransmitters like glutamate into the synapse, neurons also release a small peptide called amyloid beta. Normally, amyloid beta is cleared away metabolized by microglia, the janitor cells of our brains. While the molecular causes of Alzheimer's are still debated, most neuroscientists believe that the disease begins when amyloid beta begins to accumulate. Too much is released, or not enough is cleared away, and the synapse begins to pile up with amyloid beta. And when this happens, it binds to itself, forming sticky aggregates called amyloid plaques. 让我们把突触放大， 看一则动画演示。 在信息沟通的过程中， 除了释放谷氨酸等神经递质到突触， 神经元还释放了一种 名为β淀粉样蛋白的小肽。 正常情况下，β淀粉样蛋白 在新陈代谢时会被清除， 由我们大脑的看护细胞 小神经胶质细胞处理。 尽管分子层面引发 老年痴呆的原因还争论不休， 大多数神经学家相信 β淀粉样蛋白的累积引发了老年痴呆。 释放了太多，或者是未能完全清理， 突触因此便开始堆积β淀粉样蛋白。 若这一事件发生 突触逐渐束缚了自己， 产生一种叫做淀粉样斑块 的黏糊糊的聚合体。 How many people here are 40 years old or older? You're afraid to admit it now. This initial step into the disease, this presence of amyloid plaques accumulating, can already be found in your brains. The only way we could be sure of this would be through a PET scan, because at this point, you are blissfully unaware. You're not showing any impairments in memory, language, or cognition ... yet. We think it takes at least 15 to 20 years of amyloid plaque accumulation before it reaches a tipping point, then triggering a molecular cascade that causes the clinical symptoms of the disease. Prior to the tipping point, your lapses in memory might include things like, 'Why did I come in this room?' or 'Oh ... what's his name?' or 'Where did I put my keys?' 在座的有多少人已经四十多岁了？ 你不想承认了吗？ 老年痴呆症的起步， 淀粉样斑块的累积， 也许已经在你的大脑初步产生。 我们唯一能确认的方式是PET扫描， 因为现在你对此毫无知觉。 你还没有任何记忆、 语言、或是认知方面的问题... 现在还没有。 我们认为淀粉样斑块的累积 至少需要15至20年时间 才会到达它的临界点， 随后引发分子的连锁反应 导致了这一疾病的临床症状。 在这一临界点之前， 你的记忆衰退可能会像这样： “我为什么到这间屋子来？” 或是“呃，他叫什么来着？” 或是“我把钥匙放哪了？” Now, before you all start freaking out again, because I know half of you did at least one of those in the last 24 hours -- these are all normal kinds of forgetting. In fact, I would argue that these examples might not even involve your memory, because you didn't pay attention to where you put your keys in the first place. After the tipping point, the glitches in memory, language and cognition are different. Instead of eventually finding your keys in your coat pocket or on the table by the door, you find them in the refrigerator, or you find them and you think, 'What are these for?' 现在，在你们惊慌失措之前， 我知道你们中的半数在过去的 24小时内至少有过上述之一， 这些都是正常的遗忘类型。 实际上，我的看法是这些示例， 甚至都与你的记忆没什么关系， 因为起初你并没有在意 你把钥匙放在哪里。 在临界点之后， 记忆、语言和认知的偏差是不一样的。 最后发现钥匙并不在你的大衣口袋， 或是不在门边的桌上， 你在冰箱里找到了你的钥匙， 或者你找到钥匙后想， “这玩意是干嘛的？” So what happens when amyloid plaques accumulate to this tipping point? Our microglia janitor cells become hyper-activated, releasing chemicals that cause inflammation and cellular damage. We think they might actually start clearing away the synapses themselves. A crucial neural transport protein called 'tau' becomes hyperphosphorylated and twists itself into something called 'tangles,' which choke off the neurons from the inside. By mid-stage Alzheimer's, we have massive inflammation and tangles and all-out war at the synapse and cell death. 所以当淀粉样斑块积累到 临界点后会发生什么？ 我们的看护细胞小神经 胶质细胞变得过度活跃， 释放出导致炎症和 细胞损伤的化学物质。 我们认为这可能会 清除突触本身。 一种叫做tau蛋白的神经 转运蛋白变得过度磷酸化 并转化成叫做神经纤维缠结的物质， 从内部阻塞了神经元。 在老年痴呆症的中期， 大量的炎症和神经纤维缠结 以及突触处的全面战争 以及细胞的凋亡。 So if you were a scientist trying to cure this disease, at what point would you ideally want to intervene? Many scientists are betting big on the simplest solution: keep amyloid plaques from reaching that tipping point, which means that drug discovery is largely focused on developing a compound that will prevent, eliminate, or reduce amyloid plaque accumulation. So the cure for Alzheimer's will likely be a preventative medicine. We're going to have to take this pill before we reach that tipping point, before the cascade is triggered, before we start leaving our keys in the refrigerator. We think this is why, to date, these kinds of drugs have failed in clinical trials -- not because the science wasn't sound, but because the people in these trials were already symptomatic. It was too late. Think of amyloid plaques as a lit match. At the tipping point, the match sets fire to the forest. Once the forest is ablaze, it doesn't do any good to blow out the match. You have to blow out the match before the forest catches fire. 如果你是一位想要 治愈该病的科学家， 最佳介入时机是什么时候呢？ 许多科学家赌在了 最简单的解决方法上： 避免淀粉样斑块达到临界点， 也就意味着药物研发 很大程度上聚焦于 研发一种可以预防、消除 或是减少淀粉样斑块积累的化合物。 所以老年痴呆症的治疗方法 很有可能是一种预防性的药物。 我们需要在临界点到达之前， 在连锁反应产生之前， 在我们把钥匙落在冰箱前 服用这种药物。 我们认为这也是迄今为止 这类药物在临床试验上 失败的原因。 并不是因为科学技术不够可靠， 而是因为在临床试验的人们 都已是老年痴呆的患者。 这就为时已晚。 试想淀粉样斑块是已经点燃的火柴。 在临界点后，火柴的火引燃了整片森林。 一旦森林起火， 吹灭火柴早已于事无补。 你需要在火柴引燃 森林前就把火柴熄灭。 Even before scientists sort this out, this information is actually really good news for us, because it turns out that the way we live can influence the accumulation of amyloid plaques. And so there are things we can do to keep us from reaching that tipping point. 即使科学家还尚未解决问题， 这一好消息确实振奋人心， 因为这证明了我们的生活方式 可以影响淀粉样斑块的积累。 我们可以做许多小事 来避免达到临界点。 Let's picture your risk of Alzheimer's as a see-saw scale. We're going to pile risk factors on one arm, and when that arm hits the floor, you are symptomatic and diagnosed with Alzheimer's. Let's imagine you're 50 years old. You're not a spring chicken anymore, so you've accumulated some amyloid plaques with age. Your scale is tipped a little bit. 不妨把患老年痴呆的风险比作天平。 把可能增加风险的因素放在一端， 如果一端触到地面，那么你将患病。 并被诊断为老年痴呆。 假设你已五十岁。 你已不再年轻， 随年岁增长你已积累了部分淀粉样斑块。 你的天平已经微微倾斜。 Now let's look at your DNA. We've all inherited our genes from our moms and our dads. Some of these genes will increase our risk and some will decrease it. If you're like Alice in 'Still Alice,' you've inherited a rare genetic mutation that cranks out amyloid beta, and this alone will tip your scale arm to the ground. But for most of us, the genes we inherit will only tip the arm a bit. For example, APOE4 is a gene variant that increases amyloid, but you can inherit a copy of APOE4 from mom and dad and still never get Alzheimer's, which means that for most of us, our DNA alone does not determine whether we get Alzheimer's. So what does? We can't do anything about getting older or the genes we've inherited. So far, we haven't changed our brain's destiny. 现在观察一下你的DNA。 我们的基因全部遗传自我们的父母。 一些基因会增加风险 还有一些会降低风险。 如果你像《依然爱丽丝》中的爱丽丝一样， 你遗传的一种罕见的基因突变， 粗制滥造着β淀粉样蛋白， 单单这一点就会使你的天平一端着地。 不过对于大多数人而言 该基因只会使天平稍稍倾斜。 举个例子，APOE4是一种 增加淀粉样蛋白的变异基因， 你可能会从父母那里 遗传一份APOE4的基因 不过却不会患上老年痴呆， 这也就意味着对大多数人而言， 我们的DNA并不是决定 老年痴呆的唯一要素。 那么什么决定呢？ 我们对于衰老无能为力 也无法决定我们遗传的基因。 到现在我们还没有 改变我们大脑的宿命。 What about sleep? In slow-wave deep sleep, our glial cells rinse cerebral spinal fluid throughout our brains, clearing away metabolic waste that accumulated in our synapses while we were awake. Deep sleep is like a power cleanse for the brain. But what happens if you shortchange yourself on sleep? Many scientists believe that poor sleep hygiene might actually be a predictor of Alzheimer's. A single night of sleep deprivation leads to an increase in amyloid beta. And amyloid accumulation has been shown to disrupt sleep, which in turn causes more amyloid to accumulate. And so now we have this positive feedback loop that's going to accelerate the tipping of that scale. 关于睡眠呢？ 在慢波深度睡眠时， 我们的神经胶质细胞 冲洗着我们大脑中的脑脊液， 清除掉积累在突触的代谢废物 当我们清醒时。 深度睡眠就好像是大脑的强效净化。 那么如果你在睡眠方面亏待了自己呢？ 许多科学家坚信 不良的睡眠卫生可能 是老年痴呆的前兆。 缺乏仅仅一晚的睡眠就会 增加β淀粉样蛋白。 而淀粉样蛋白的累积 已被证实会影响睡眠， 从而导致了更多淀粉样蛋白的累积。 所以现在我们有了正反馈循环， 将会加剧天平的倾倒。 What else? Cardiovascular health. High blood pressure, diabetes, obesity, smoking, high cholesterol, have all been shown to increase our risk of developing Alzheimer's. Some autopsy studies have shown that as many as 80 percent of people with Alzheimer's also had cardiovascular disease. Aerobic exercise has been shown in many studies to decrease amyloid beta in animal models of the disease. So a heart-healthy Mediterranean lifestyle and diet can help to counter the tipping of this scale. 还有别的吗？ 心血管的健康。 高血压、糖尿病、肥胖、 吸烟、高胆固醇， 这些都证明会增加患老年痴呆的风险。 一些验尸报告表明 有80%的老年痴呆患者 同样患有心血管疾病。 许多研究表明有氧运动 在该病的动物模型试验中 可以有效减少β淀粉样蛋白。 所以有益心脏健康的 地中海式生活方式和饮食 可以有效扳回倾斜的天平。 So there are many things we can do to prevent or delay the onset of Alzheimer's. But let's say you haven't done any of them. Let's say you're 65; there's Alzheimer's in your family, so you've likely inherited a gene or two that tips your scale arm a bit; you've been burning the candle at both ends for years; you love bacon; and you don't run unless someone's chasing you. 所以我们能做很多事 来预防或者延缓老年痴呆症的到来。 不过假设你并没有做任何事。 并且你已经六十五岁了， 你的家庭中有老年痴呆的患者 所以你可能遗传了一两种 可能会倾斜天平的基因， 你的生命之火渐渐微弱， 你喜欢培根， 除非有人追你你懒得跑动。 Let's imagine that your amyloid plaques have reached that tipping point. Your scale arm has crashed to the floor. You've tripped the cascade, setting fire to the forest, causing inflammation, tangles, and cell death. You should be symptomatic for Alzheimer's. You should be having trouble finding words and keys and remembering what I said at the beginning of this talk. But you might not be. 假设你的淀粉样斑块已经达到临界点。 你天平的一端已坠地。 你触发了连锁反应， 引发了森林火灾， 导致了炎症、神经纤维 缠结以及细胞凋亡。 你表现出老年痴呆的症状。 你在措辞和找钥匙时会碰到麻烦 并且回想不起我一开始讲的内容。 也许你不会这样。 There's one more thing you can do to protect yourself from experiencing the symptoms of Alzheimer's, even if you have the full-blown disease pathology ablaze in your brain. It has to do with neural plasticity and cognitive reserve. Remember, the experience of having Alzheimer's is ultimately a result of losing synapses. The average brain has over a hundred trillion synapses, which is fantastic; we've got a lot to work with. And this isn't a static number. We gain and lose synapses all the time, through a process called neural plasticity. Every time we learn something new, we are creating and strengthening new neural connections, new synapses. 另外还有一件事可以帮助你 免于老年痴呆的症状， 哪怕你的大脑已病入膏肓。 它需解决神经可塑性 和认知储备问题。 记住，老年痴呆症的发作 是突触损失的最终后果。 一般大脑有超过万亿的突触， 这很不可思议， 我们有这么庞大的数量。 而这一数字不是一成不变。 我们在一个叫做神经可塑性的过程之中， 不断生成和消耗着突触。 每当我们习得新东西， 我们建立并强化新的神经连接， 新的突触产生了。 In the Nun Study, 678 nuns, all over the age of 75 when the study began, were followed for more than two decades. They were regularly given physical checkups and cognitive tests, and when they died, their brains were all donated for autopsy. In some of these brains, scientists discovered something surprising. Despite the presence of plaques and tangles and brain shrinkage -- what appeared to be unquestionable Alzheimer's -- the nuns who had belonged to these brains showed no signs of having the disease while they were alive. 在Nun研究中， 研究开始时，678位修女全都年过七十五岁， 进行了二十多年的研究。 她们会定期接受身体检查和认知测试， 如果不行去世，她们的大脑 都捐献出去用于验尸。 科学家们在一些大脑中 发现了一些神奇的东西。 尽管样斑块、神经纤维 缠结和大脑的萎缩， 这些现象似乎是老年痴呆症无疑， 然而这些大脑的主人 那些修女却没有在生前 表现出患有老年痴呆的症状。 How can this be? We think it's because these nuns had a high level of cognitive reserve, which is a way of saying that they had more functional synapses. People who have more years of formal education, who have a high degree of literacy, who engage regularly in mentally stimulating activities, all have more cognitive reserve. They have an abundance and a redundancy in neural connections. So even if they have a disease like Alzheimer's compromising some of their synapses, they've got many extra backup connections, and this buffers them from noticing that anything is amiss. 这是怎么回事呢？ 我们认为这是因为这些 修女拥有高级的认知储备， 意味着她们有功能更强的突触。 接受正式教育的时间越长的人， 拥有较强读写能力的人， 定期参加刺激心理活动的人， 这些人都有更高的认知储备。 他们有着大量甚至多余的神经连接。 所以即使他们患上老年痴呆等疾病 损伤了部分突触， 他们依然有充足的额外后备连接， 而这减缓了他们的大脑产生混乱。 Let's imagine a simplified example. Let's say you only know one thing about a subject. Let's say it's about me. You know that Lisa Genova wrote 'Still Alice,' and that's the only thing you know about me. You have that single neural connection, that one synapse. Now imagine you have Alzheimer's. You have plaques and tangles and inflammation and microglia devouring that synapse. Now when someone asks you, 'Hey, who wrote 'Still Alice?'' you can't remember, because that synapse is either failing or gone. You've forgotten me forever. 让我们来看一个简单的例子。 假设你只知道关于某一主题的一件事。 比方说是关于我的。 你知道丽莎·吉诺瓦 写下了《依然爱丽丝》， 这是你唯一知道的关于我的事。 你拥有一处单一的神经连接， 那一个特定突触。 如果现在你患上了老年痴呆。 你有样斑块、神经纤维缠结和炎症 以及小神经胶质细胞吞噬了那一突触。 现在若有人问起你 “嘿，谁写了《依然爱丽丝》？“ 你无法回想起来了， 因为那个突触要么衰弱要么消失了。 你把我忘得一干二净。 But what if you had learned more about me? Let's say you learned four things about me. Now imagine you have Alzheimer's, and three of those synapses are damaged or destroyed. You still have a way to detour the wreckage. You can still remember my name. So we can be resilient to the presence of Alzheimer's pathology through the recruitment of yet-undamaged pathways. And we create these pathways, this cognitive reserve, by learning new things. Ideally, we want these new things to be as rich in meaning as possible, recruiting sight and sound and associations and emotion. 但是如果你对我了解更深呢？ 比如你了解我的四件事情。 现在如果你患上了老年痴呆， 即使三处突触已损伤或者毁坏。 你依然有一条路来 绕过阻碍找到我的信息。 你依然记得我的名字。 所以我们可以通过使用那些未损坏的通路 有效应对老年痴呆。 同时我们通过学习新事物， 创造了新的通路，改变着认知储备。 理想情况下，我们希望 这些新事物的意义尽可能丰富， 吸纳视觉与听觉的联合感受。 So this really doesn't mean doing crossword puzzles. You don't want to simply retrieve information you've already learned, because this is like traveling down old, familiar streets, cruising neighborhoods you already know. You want to pave new neural roads. Building an Alzheimer's-resistant brain means learning to speak Italian, meeting new friends, reading a book, or listening to a great TED Talk. 所以这并不意味着 去做横纵字谜游戏。 你不希望去重拾 那些你早已学会的信息， 这就好比游览老旧的熟悉街道， 那些周边环境你早已了然于心。 你想要开辟新的神经道路。 使你的大脑抵抗老年痴呆 意味着学习说意大利语， 去遇见新朋友， 读一本书， 或是听一场精彩的TED演讲。 And if, despite all of this, you are someday diagnosed with Alzheimer's, there are three lessons I've learned from my grandmother and the dozens of people I've come to know living with this disease. Diagnosis doesn't mean you're dying tomorrow. Keep living. You won't lose your emotional memory. You'll still be able to understand love and joy. You might not remember what I said five minutes ago, but you'll remember how I made you feel. And you are more than what you can remember.Thank you. 如果做了所有的这一切之后 有一天你被诊断为老年痴呆， 我从我的祖母以及我认识的许多患者中 学习到了三件事情。 诊断并不意味着死期将至。 顽强地活下去吧。 你不会丢失你的情感记忆。 你依然可以理解爱与喜悦。 你也许不会记得我五分钟前的话语， 但是你依然会记得我带给你的感受。 你远胜于你所能记住的一切。谢谢。 |
|
|
