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.
在場有多少人 希望能活到 80 歲以上? 是的。 我想我們都有這個期望, 期望能活得很久。 讓我們穿越到未來, 想像一下未來的你們, 想像我們現在全都已變成 85 歲。 現在,每個人分別看向兩個人, 你們之中其中一個 可能就有阿茲海默症。
(Laughter)
(笑聲)
Alright, alright. And maybe you're thinking, "Well, it won't be me." Then, OK. You are a caregiver. So --
好了,好了。 也許你們在想 「好吧,那不會是我。」 那麼,沒關係, 你會是那個照顧他的人。 所以......
(Laughter)
(笑聲)
so in some way, this terrifying disease is likely to affect us all.
所以就某方面而言, 這個可怕的疾病 可能會影響我們每一個人。
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.
對於阿茲海默症的恐懼 部分源於我們對這疾病的無能為力。 儘管已有數十年的研究, 我們仍未找到改善它的治療方式, 也沒辦法徹底治癒它。 所以假如我們有幸活得很久, 罹患阿茲海默症似乎就是 我們大腦的宿命。
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?
但也並非得如此。 假如我說我們能改變這些數據, 徹底改變我們大腦的宿命, 而不需要依靠任何 藥物的治療或改善呢?
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.
讓我們先看看目前 我們對阿茲海默症神經學上的了解。 這是兩個神經元連結的圖片。 它們的連結點, 也就是紅色圈的這個地方 叫作突觸。 突觸就是神經傳導物釋放的地方。 訊號在這裡被傳遞、 產生交流的地方。 這裡是我們思考、感覺、 看、聽、產生慾望...... 和記憶的地方。 而突觸也是阿茲海默症 發病的地方,
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.
讓我們放大來看突觸, 看看這個現象的卡通示意圖。 在傳訊的過程中, 除了釋放神經傳導物, 如:麩胺酸,到突觸中。 神經元也會釋放一種小分子蛋白質, 叫作 β-類澱粉蛋白。 通常,β-類澱粉蛋白 會被微膠細胞代謝清除, 微膠細胞就像我們大腦的清潔工。 儘管分子層面引發 阿茲海默症的原因仍爭論不休, 但大多數的神經學家相信 此疾病發作的起源, 就是在 β-類澱粉蛋白 開始累積的時候。 當他們被釋放太多, 或被清除掉的不夠多, β-類澱粉蛋白就開始堆積在突觸。 當此狀況發生,它就會凝結, 形成黏性凝聚物, 叫作澱粉樣蛋白斑。
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?"
現場有多少人的年紀 是 40 歲或以上? 現在大家都害怕承認了? 這就是疾病的最初階段, 澱粉樣蛋白斑累積的現象 可能已存在你們的大腦中, 我們唯一可以確認的方法 是透過「正子掃描」, 因為現在你對此毫無知覺, 你尚未有任何記憶、 語言或認知方面衰退的現象...... 但……只是尚未。 我們認為澱粉樣蛋白斑的累積 至少需要 15 到 20 年, 才能到達臨界點, 隨後引發分子的連鎖反應, 而造成了阿茲海默症的臨床症狀。 在到達臨界點之前, 你的記憶衰退可能會像這樣: 「我為甚麼要走進這個房間來?」 或「喔......他叫甚麼名字?」 或「我把鑰匙放在了哪裡?」
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?"
現在,在你們驚慌失措之前, 我知道你們中的半數, 在過去 24 小時之內 至少曾經經歷過 上述的其中一件事情, 這些都是正常的遺忘症狀。 事實上,上述這些例子 可能根本與你的記憶無關, 因為你第一時間, 並不會去注意到 你把鑰匙放到哪裡。 一旦臨界點發生之後, 你的記憶、語言和認知上的偏差 就會變得不同了。 你最後才知道鑰匙 並非在你的外套口袋裡, 也並非門旁的桌子上, 而是你把它放在冰箱裡了, 或者,你找到它後,你卻在想: 「這東西是用來做甚麼用的?」
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.
當澱粉樣蛋白斑累積到臨界點時, 到底會發生甚麼事? 我們的微膠細胞清潔工 會變得極度活躍, 它們會釋放出化學物質, 造成發炎和細胞的損壞。 我們認為它們正在清除的 就是突觸本身。 有一個重要的神經傳導蛋白叫做 「tau 蛋白」會被過磷酸化, 並把自己轉變成一種叫 「纖維纏結」的東西, 從內部堵塞神經元。 到了中期的阿茲海默症, 我們的突觸會發生 大量的發炎並糾纏在一起, 然後細胞就會死亡。
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.
假如你是科學家, 試著要治療這個疾病, 最佳的介入時機是甚麼時候呢? 許多科學家賭在 最簡單的解決方案上: 避免澱粉樣蛋白斑累積到臨界點, 也就是說,大部分的 藥物治療主要是研究化合物 利用它們來預防、消除或減少 澱粉樣蛋白斑的累積。 所以他們研發的藥物, 都只是一些預防老年癡呆的藥物。 我們會在達到臨界點之前、 在分子連鎖反應產生之前、 在我們開始把鑰匙 遺忘在冰箱裡之前服用這些藥物。 我們認為這是目前為止 這些藥物在臨床實驗中 失敗的原因…… 並不是科學不夠可靠, 而是因為實驗對象都已經有症狀了。 已經太遲了。 試想澱粉樣蛋白斑 是一根已經點燃的火柴棒。 到了臨界點時,火柴棒點燃了森林。 一旦森林著火, 把火柴棒吹熄已於事無補。 你必須在森林著火之前就吹熄火柴。
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.
即使科學家尚未找到解決方法, 但這個消息確實振奮人心, 因為它證明了我們生活的方式 會影響澱粉樣蛋白的累積。 我們可以做一些事情, 來避免自己達到臨界點。
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.
讓我們把罹患老年癡呆的風險 比作是蹺蹺板。 我們把造成風險的因素 放在蹺蹺板的其中一邊, 當這一邊碰到地面, 那麼症狀就會出現, 然後被診斷為阿茲海默症。 假設你已經 50 歲。 你已不再年輕, 隨著年紀增長,你已經 累積了一些澱粉狀蛋白班。 你的蹺蹺板已稍微傾斜。
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.
現在我們來看看你的 DNA。 我們從父母那裡繼承了基因。 有些基因會增加風險而有些會減少。 如果你們像電影《我想念我自己》 中的女主角愛莉絲一樣, 遺傳了罕見的基因突變, 不正常地大量增生 β-類澱粉蛋白, 這會讓你的蹺蹺板一端墜落到地面, 但對大多數人來說, 我們遺傳到的基因 只會讓蹺蹺板稍微傾斜。 舉例來說,APOE4 是一個 會增生澱粉樣蛋白斑的變種基因, 但你可能從父母那裡 遺傳了 APOE4, 卻不會得到阿茲海默症, 也就是說對大多數人來說, 光憑我們的 DNA 並不能決定 我們是否會得阿茲海默症。 那麼甚麼能決定呢? 我們對於衰老無能為力, 也無法決定我們遺傳的基因。 目前為止,我們仍無法改變 大腦的宿命。
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.
那麼睡覺呢? 在慢波深眠中,我們的神經膠細胞 會在我們的大腦中,沖洗腦脊液。 當我們清醒的時候, 它會清除掉累積在突觸的 代謝廢物。 深度睡眠就好像大腦的強效淨化。 假如你稍微改變 睡眠方式會發生甚麼事? 許多科學家相信, 糟糕的睡眠狀況 可能會導致阿茲海默症。 僅僅一個晚上的睡眠不足就會導致 β-類澱粉蛋白的增生。 而澱粉樣蛋白斑的累積 已被證實會干擾睡眠, 結果導致更多澱粉樣蛋白斑的累積。 成為一個惡性循環, 加劇了蹺蹺板的傾斜。
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.
還有甚麼? 心血管健康。 高血壓、糖尿病、過重、 抽菸、高膽固醇, 全都會增加罹患阿茲海默症的風險。 病理剖析的研究報告顯示, 罹患阿茲海默的人群中, 多達 80% 的病患, 同時擁有心血管疾病。 許多阿茲海默症的 動物模擬實驗研究中顯示, 有氧運動可以減少 β-類澱粉蛋白的數量。 所以有益身心健康的 地中海式生活飲食方式, 可以幫忙抵抗蹺蹺板的傾斜。
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.
所以我們有很多事可以做, 來預防或延緩老年痴呆症的到來。 但假設你甚麼事都沒做。 假設你已 65 歲; 你有阿茲海默症的家族病史, 所以你很可能帶有阿茲海默基因, 這會讓你的蹺蹺板傾斜一點點; 你已經蠟燭兩頭燒了好幾年; 你愛吃培根; 你也不去跑步,除非有人在追你。
(Laughter)
(笑)
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.
想像你的澱粉樣蛋白斑 已經累積到臨界點。 你的蹺蹺板已經墜落到地面。 你觸發了連鎖反應, 引發了森林大火, 你開始出現發炎、 神經纏結和細胞凋亡的情況。 你的阿茲海默症已經病發。 你開始會造詞困難、找不到鑰匙, 記不得我在演講剛開始時 到底說了些甚麼。 但你也可能不會這樣。
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.
你還可以做一件事來保護自己, 來避免阿茲海默症狀出現, 那怕你的大腦已病入膏肓, 它仍然跟神經可塑性 和認知儲備有關。 記住,老年痴呆症發作的根本原因 就是突觸已經被破壞了。 大腦平均擁有超過百萬億個突觸, 這很奇妙;我們要處理 這麼龐大的數目。 而這不是一個不變的數目。 我們的突觸數目隨時都在增減, 透過一個叫做 「神經可塑性」的過程。 每當我們學到新東西, 我們就會創造和強化新的神經連結, 和新的突觸。
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.
在我們以修女為研究對象 進行的研究當中, 實驗開始時,678 位 全超過 75 歲的修女, 將會被追蹤調查超過 20 年。 她們會定期接受 健康檢查和認知測試, 當她們死後,她們的大腦 會捐贈出來做病理解剖。 科學家們在其中一些大腦中 發現了不可思議的東西。 儘管那些大腦中有澱粉樣蛋白斑、 神經纏結和大腦收縮的情況, 這很明顯的,根本就是 阿茲海默症的典型病狀, 但擁有這些大腦的修女, 她們在世時, 卻沒有表現出阿茲海默症的症狀。
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.
怎麼會這樣? 我們認為那是因為這些修女 擁有高度的認知儲備量, 也就是說他們有較多 運作良好的突觸。 接受正規教育較多年的人、 擁有較高學歷的人、 和會定期參與 促進精神刺激活動的人, 都會有較多的認知儲備量。 他們有充裕的神經連結。 所以即使他們因為患有像 阿茲海默那樣的疾病, 使她們減少了一些突觸, 她們還有很多備用的連結, 從而減緩她們的大腦產生混亂。
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.
讓我們假想一個簡單的例子。 假設你對一個主題只有一個認知。 假設那個主題就是我。 你知道麗莎.吉諾瓦寫了一本 《我想念我自己》, 而這是你對我唯一的認知。 你對我的認知, 只有單一個神經連結, 單一個突觸。 現在假設你有阿茲海默症。 你有澱粉樣蛋白斑、 神經纏結和發炎的情況, 你的微膠細胞吞噬了突觸。 現在當有人問你, 「嘿,誰寫了《我想念我自己》?」 你不記得了, 因為那個突觸不是失效就是不見了, 你就會永遠忘記我。
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.
但假如你對我了解更深呢? 比如,你了解我四件事情。 現在想像一下,你得了阿茲海默症, 其中三個突觸被破壞了。 你仍有一條可以繞過那些 被破壞的突觸的路線。 你仍能記得我的名字。 所以當我們有阿茲海默症的 病理狀況發生, 藉由使用那些尚未受損的神經通道, 我們仍有可能可以復原, 我們可以藉由學習新事物, 創造出新的通路、 增加認知的儲備量。 理想上,我們希望這些新事物 越有豐富的意義越好, 越能喚起我們的視覺、 聽覺、聯系和情感越好。
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.
我的意思並非要你去做拼字遊戲。 你不會想只是重拾你 已學習過的記憶, 因為這就好比遊覽 老舊而熟悉的街頭, 那些周邊環境你已了然於心。 你要鋪設新的神經通路。 建造一個能抵禦阿茲海默症的大腦, 像是去學習義大利語、 去交新朋友、 讀一本書, 或聆聽超讚的 TED 演講。
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.
假如,儘管做了這些事, 你還是會在某一天 被診斷出阿茲海默症, 我從我祖母 和許多我認識的阿茲海默症患者 那兒學到了三件事。 被診斷出阿茲海默症 並不代表你明天就會死掉。 繼續活下去。 你不會喪失你的情感記憶。 你仍能理解愛與歡樂。 你可能不會記得 五分鐘前我說了甚麼, 但你會記得我讓你感受到了甚麼。 你本身,比你能記得的 東西更有意義。
Thank you.
謝謝。
(Applause)
(掌聲)