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  • How many people here would like to live to be at least 80 years old?

    在場有多少人 希望能活到 80 歲以上?

  • Yeah.

    是的。

  • I think we all have this hopeful expectation

    我想我們都有這個期望,

  • of living into old age.

    期望能活得很久。

  • Let's project out into the future,

    讓我們穿越到未來,

  • to your future "you's,"

    想像一下未來的你們,

  • and let's imagine that we're all 85.

    想像我們現在全都已變成 85 歲。

  • Now, everyone look at two people.

    現在,每個人分別看向兩個人,

  • One of you probably has Alzheimer's disease.

    你們之中其中一個 可能就有阿茲海默症。

  • (Laughter)

    (笑聲)

  • Alright, alright.

    好了,好了。

  • And maybe you're thinking, "Well, it won't be me."

    也許你們在想 「好吧,那不會是我。」

  • Then, OK. You are a caregiver.

    那麼,沒關係, 你會是那個照顧他的人。

  • So --

    所以......

  • (Laughter)

    (笑聲)

  • so in some way,

    所以就某方面而言,

  • this terrifying disease is likely to affect us all.

    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

    對於阿茲海默症的恐懼

  • that there's nothing we can do about it.

    部分源於我們對這疾病的無能為力。

  • Despite decades of research, we still have no disease-modifying treatment

    儘管已有數十年的研究, 我們仍未找到改善它的治療方式,

  • and no cure.

    也沒辦法徹底治癒它。

  • So if we're lucky enough to live long enough,

    所以假如我們有幸活得很久,

  • Alzheimer's appears to be our brain's destiny.

    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.

    但也並非得如此。

  • What if I told you we could change these statistics,

    假如我說我們能改變這些數據,

  • literally change our brain's destiny,

    徹底改變我們大腦的宿命,

  • without relying on a cure or advancements in medicine?

    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

    讓我們先看看目前

  • about the neuroscience of Alzheimer's.

    我們對阿茲海默症神經學上的了解。

  • Here's a picture of two neurons connecting.

    這是兩個神經元連結的圖片。

  • The point of connection, this space circled in red,

    它們的連結點, 也就是紅色圈的這個地方

  • is called the synapse.

    叫作突觸。

  • The synapse is where neurotransmitters are released.

    突觸就是神經傳導物釋放的地方。

  • This is where signals are transmitted, where communication happens.

    訊號在這裡被傳遞、 產生交流的地方。

  • This is where we think, feel, see, hear, desire ...

    這裡是我們思考、感覺、 看、聽、產生慾望......

  • and remember.

    和記憶的地方。

  • And the synapse is where Alzheimer's happens.

    而突觸也是阿茲海默症 發病的地方,

  • Let's zoom in on the synapse

    讓我們放大來看突觸,

  • and look at a cartoon representation of what's going on.

    看看這個現象的卡通示意圖。

  • During the business of communicating information,

    在傳訊的過程中,

  • in addition to releasing neurotransmitters like glutamate into the synapse,

    除了釋放神經傳導物, 如:麩胺酸,到突觸中。

  • neurons also release a small peptide called amyloid beta.

    神經元也會釋放一種小分子蛋白質, 叫作 β-類澱粉蛋白。

  • Normally, amyloid beta is cleared away metabolized by microglia,

    通常,β-類澱粉蛋白 會被微膠細胞代謝清除,

  • the janitor cells of our brains.

    微膠細胞就像我們大腦的清潔工。

  • While the molecular causes of Alzheimer's are still debated,

    儘管分子層面引發 阿茲海默症的原因仍爭論不休,

  • most neuroscientists believe that the disease begins

    但大多數的神經學家相信 此疾病發作的起源,

  • when amyloid beta begins to accumulate.

    就是在 β-類澱粉蛋白 開始累積的時候。

  • Too much is released, or not enough is cleared away,

    當他們被釋放太多, 或被清除掉的不夠多,

  • and the synapse begins to pile up with amyloid beta.

    β-類澱粉蛋白就開始堆積在突觸。

  • And when this happens, it binds to itself,

    當此狀況發生,它就會凝結,

  • forming sticky aggregates called amyloid plaques.

    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?

    現場有多少人的年紀 是 40 歲或以上?

  • You're afraid to admit it now.

    現在大家都害怕承認了?

  • This initial step into the disease,

    這就是疾病的最初階段,

  • this presence of amyloid plaques accumulating,

    澱粉樣蛋白斑累積的現象

  • can already be found in your brains.

    可能已存在你們的大腦中,

  • The only way we could be sure of this would be through a PET scan,

    我們唯一可以確認的方法 是透過「正子掃描」,

  • because at this point, you are blissfully unaware.

    因為現在你對此毫無知覺,

  • You're not showing any impairments in memory, language, or cognition ...

    你尚未有任何記憶、 語言或認知方面衰退的現象......

  • yet.

    但……只是尚未。

  • We think it takes at least 15 to 20 years of amyloid plaque accumulation

    我們認為澱粉樣蛋白斑的累積 至少需要 15 到 20 年,

  • before it reaches a tipping point,

    才能到達臨界點,

  • then triggering a molecular cascade

    隨後引發分子的連鎖反應,

  • that causes the clinical symptoms of the disease.

    而造成了阿茲海默症的臨床症狀。

  • Prior to the tipping point,

    在到達臨界點之前,

  • your lapses in memory might include things like,

    你的記憶衰退可能會像這樣:

  • "Why did I come in this room?"

    「我為甚麼要走進這個房間來?」

  • or "Oh ... what's his name?"

    或「喔......他叫甚麼名字?」

  • or "Where did I put my keys?"

    或「我把鑰匙放在了哪裡?」

  • Now, before you all start freaking out again,

    現在,在你們驚慌失措之前,

  • because I know half of you did at least one of those in the last 24 hours --

    我知道你們中的半數, 在過去 24 小時之內

  • these are all normal kinds of forgetting.

    至少曾經經歷過 上述的其中一件事情,

  • In fact, I would argue that these examples

    這些都是正常的遺忘症狀。

  • might not even involve your memory,

    事實上,上述這些例子

  • because you didn't pay attention to where you put your keys

    可能根本與你的記憶無關,

  • in the first place.

    因為你第一時間,

  • After the tipping point,

    並不會去注意到 你把鑰匙放到哪裡。

  • the glitches in memory, language and cognition are different.

    一旦臨界點發生之後,

  • Instead of eventually finding your keys in your coat pocket

    你的記憶、語言和認知上的偏差 就會變得不同了。

  • or on the table by the door,

    你最後才知道鑰匙 並非在你的外套口袋裡,

  • you find them in the refrigerator,

    也並非門旁的桌子上,

  • or you find them and you think,

    而是你把它放在冰箱裡了,

  • "What are these for?"

    或者,你找到它後,你卻在想:

  • So what happens when amyloid plaques accumulate to this tipping point?

    「這東西是用來做甚麼用的?」

  • Our microglia janitor cells become hyper-activated,

    當澱粉樣蛋白斑累積到臨界點時, 到底會發生甚麼事?

  • releasing chemicals that cause inflammation and cellular damage.

    我們的微膠細胞清潔工 會變得極度活躍,

  • We think they might actually start clearing away

    它們會釋放出化學物質, 造成發炎和細胞的損壞。

  • the synapses themselves.

    我們認為它們正在清除的

  • A crucial neural transport protein called "tau" becomes hyperphosphorylated

    就是突觸本身。

  • and twists itself into something called "tangles,"

    有一個重要的神經傳導蛋白叫做 「tau 蛋白」會被過磷酸化,

  • which choke off the neurons from the inside.

    並把自己轉變成一種叫 「纖維纏結」的東西,

  • By mid-stage Alzheimer's, we have massive inflammation and tangles

    從內部堵塞神經元。

  • and all-out war at the synapse

    到了中期的阿茲海默症,

  • and cell death.

    我們的突觸會發生 大量的發炎並糾纏在一起,

  • So if you were a scientist trying to cure this disease,

    然後細胞就會死亡。

  • at what point would you ideally want to intervene?

    假如你是科學家, 試著要治療這個疾病,

  • Many scientists are betting big on the simplest solution:

    最佳的介入時機是甚麼時候呢?

  • keep amyloid plaques from reaching that tipping point,

    許多科學家賭在 最簡單的解決方案上:

  • which means that drug discovery is largely focused on developing a compound

    避免澱粉樣蛋白斑累積到臨界點,

  • that will prevent, eliminate, or reduce amyloid plaque accumulation.

    也就是說,大部分的 藥物治療主要是研究化合物

  • So the cure for Alzheimer's will likely be a preventative medicine.

    利用它們來預防、消除或減少 澱粉樣蛋白斑的累積。

  • We're going to have to take this pill before we reach that tipping point,

    所以他們研發的藥物, 都只是一些預防老年癡呆的藥物。

  • before the cascade is triggered,

    我們會在達到臨界點之前、

  • before we start leaving our keys in the refrigerator.

    在分子連鎖反應產生之前、

  • We think this is why, to date, these kinds of drugs have failed

    在我們開始把鑰匙 遺忘在冰箱裡之前服用這些藥物。

  • in clinical trials --

    我們認為這是目前為止 這些藥物在臨床實驗中

  • not because the science wasn't sound,

    失敗的原因……

  • but because the people in these trials were already symptomatic.

    並不是科學不夠可靠,

  • It was too late.

    而是因為實驗對象都已經有症狀了。

  • Think of amyloid plaques as a lit match.

    已經太遲了。

  • At the tipping point, the match sets fire to the forest.

    試想澱粉樣蛋白斑 是一根已經點燃的火柴棒。

  • Once the forest is ablaze,

    到了臨界點時,火柴棒點燃了森林。

  • it doesn't do any good to blow out the match.

    一旦森林著火,

  • You have to blow out the match before the forest catches fire.

    把火柴棒吹熄已於事無補。

  • Even before scientists sort this out,

    你必須在森林著火之前就吹熄火柴。

  • this information is actually really good news for us,

    即使科學家尚未找到解決方法,

  • because it turns out that the way we live can influence the accumulation

    但這個消息確實振奮人心,

  • of amyloid plaques.

    因為它證明了我們生活的方式

  • And so there are things we can do

    會影響澱粉樣蛋白的累積。

  • to keep us from reaching that tipping point.

    我們可以做一些事情,

  • Let's picture your risk of Alzheimer's as a see-saw scale.

    來避免自己達到臨界點。

  • We're going to pile risk factors on one arm,

    讓我們把罹患老年癡呆的風險 比作是蹺蹺板。

  • and when that arm hits the floor, you are symptomatic

    我們把造成風險的因素 放在蹺蹺板的其中一邊,

  • and diagnosed with Alzheimer's.

    當這一邊碰到地面, 那麼症狀就會出現,

  • Let's imagine you're 50 years old.

    然後被診斷為阿茲海默症。

  • You're not a spring chicken anymore,

    假設你已經 50 歲。

  • so you've accumulated some amyloid plaques with age.

    你已不再年輕,

  • Your scale is tipped a little bit.

    隨著年紀增長,你已經 累積了一些澱粉狀蛋白班。

  • Now let's look at your DNA.

    你的蹺蹺板已稍微傾斜。

  • We've all inherited our genes from our moms and our dads.

    現在我們來看看你的 DNA。

  • Some of these genes will increase our risk and some will decrease it.

    我們從父母那裡繼承了基因。

  • If you're like Alice in "Still Alice,"

    有些基因會增加風險而有些會減少。

  • you've inherited a rare genetic mutation that cranks out amyloid beta,

    如果你們像電影《我想念我自己》 中的女主角愛莉絲一樣,

  • and this alone will tip your scale arm to the ground.

    遺傳了罕見的基因突變, 不正常地大量增生 β-類澱粉蛋白,

  • But for most of us, the genes we inherit will only tip the arm a bit.

    這會讓你的蹺蹺板一端墜落到地面,

  • For example, APOE4 is a gene variant that increases amyloid,

    但對大多數人來說,

  • but you can inherit a copy of APOE4 from mom and dad

    我們遺傳到的基因 只會讓蹺蹺板稍微傾斜。

  • and still never get Alzheimer's,

    舉例來說,APOE4 是一個 會增生澱粉樣蛋白斑的變種基因,

  • which means that for most of us,

    但你可能從父母那裡 遺傳了 APOE4,

  • our DNA alone does not determine whether we get Alzheimer's.

    卻不會得到阿茲海默症,

  • So what does?

    也就是說對大多數人來說,

  • We can't do anything about getting older or the genes we've inherited.

    光憑我們的 DNA 並不能決定 我們是否會得阿茲海默症。

  • So far, we haven't changed our brain's destiny.

    那麼甚麼能決定呢?

  • What about sleep?

    我們對於衰老無能為力, 也無法決定我們遺傳的基因。

  • In slow-wave deep sleep, our glial cells rinse cerebral spinal fluid

    目前為止,我們仍無法改變 大腦的宿命。

  • throughout our brains,

    那麼睡覺呢?

  • clearing away metabolic waste that accumulated in our synapses

    在慢波深眠中,我們的神經膠細胞

  • while we were awake.

    會在我們的大腦中,沖洗腦脊液。

  • Deep sleep is like a power cleanse for the brain.

    當我們清醒的時候,

  • But what happens if you shortchange yourself on sleep?

    它會清除掉累積在突觸的 代謝廢物。

  • Many scientists believe

    深度睡眠就好像大腦的強效淨化。

  • that poor sleep hygiene might actually be a predictor of Alzheimer's.

    假如你稍微改變 睡眠方式會發生甚麼事?

  • A single night of sleep deprivation leads to an increase in amyloid beta.

    許多科學家相信,

  • And amyloid accumulation has been shown to disrupt sleep,

    糟糕的睡眠狀況 可能會導致阿茲海默症。

  • which in turn causes more amyloid to accumulate.

    僅僅一個晚上的睡眠不足就會導致 β-類澱粉蛋白的增生。

  • And so now we have this positive feedback loop

    而澱粉樣蛋白斑的累積 已被證實會干擾睡眠,

  • that's going to accelerate the tipping of that scale.

    結果導致更多澱粉樣蛋白斑的累積。

  • What else?

    成為一個惡性循環,

  • Cardiovascular health.

    加劇了蹺蹺板的傾斜。

  • High blood pressure, diabetes, obesity, smoking, high cholesterol,

    還有甚麼?

  • have all been shown to increase our risk of developing Alzheimer's.

    心血管健康。

  • Some autopsy studies have shown

    高血壓、糖尿病、過重、 抽菸、高膽固醇,

  • that as many as 80 percent of people with Alzheimer's

    全都會增加罹患阿茲海默症的風險。

  • also had cardiovascular disease.

    病理剖析的研究報告顯示,

  • Aerobic exercise has been shown in many studies to decrease amyloid beta

    罹患阿茲海默的人群中, 多達 80% 的病患,

  • in animal models of the disease.

    同時擁有心血管疾病。

  • So a heart-healthy Mediterranean lifestyle and diet

    許多阿茲海默症的 動物模擬實驗研究中顯示,

  • can help to counter the tipping of this scale.

    有氧運動可以減少 β-類澱粉蛋白的數量。

  • So there are many things we can do

    所以有益身心健康的 地中海式生活飲食方式,

  • to prevent or delay the onset of Alzheimer's.

    可以幫忙抵抗蹺蹺板的傾斜。

  • But let's say you haven't done any of them.

    所以我們有很多事可以做,

  • Let's say you're 65;

    來預防或延緩老年痴呆症的到來。

  • there's Alzheimer's in your family, so you've likely inherited a gene or two

    但假設你甚麼事都沒做。

  • that tips your scale arm a bit;

    假設你已 65 歲;

  • you've been burning the candle at both ends for years;

    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,

  • you love bacon;

    這會讓你的蹺蹺板傾斜一點點;

  • and you don't run unless someone's chasing you.

    你已經蠟燭兩頭燒了好幾年;

  • (Laughter)

    你愛吃培根;

  • Let's imagine that your amyloid plaques have reached that tipping point.

    你也不去跑步,除非有人在追你。

  • Your scale arm has crashed to the floor.

    (笑)

  • You've tripped the cascade,

    想像你的澱粉樣蛋白斑 已經累積到臨界點。

  • setting fire to the forest,

    你的蹺蹺板已經墜落到地面。

  • causing inflammation, tangles, and cell death.

    你觸發了連鎖反應,

  • You should be symptomatic for Alzheimer's.

    引發了森林大火,

  • You should be having trouble finding words and keys

    你開始出現發炎、 神經纏結和細胞凋亡的情況。

  • and remembering what I said at the beginning of this talk.

    你的阿茲海默症已經病發。

  • But you might not be.

    你開始會造詞困難、找不到鑰匙,

  • There's one more thing you can do to protect yourself

    記不得我在演講剛開始時 到底說了些甚麼。

  • from experiencing the symptoms of Alzheimer's,

    但你也可能不會這樣。

  • even if you have the full-blown disease pathology ablaze in your brain.

    你還可以做一件事來保護自己,

  • It has to do with neural plasticity and cognitive reserve.

    來避免阿茲海默症狀出現,

  • Remember, the experience of having Alzheimer's

    那怕你的大腦已病入膏肓,

  • is ultimately a result of losing synapses.

    它仍然跟神經可塑性 和認知儲備有關。

  • The average brain has over a hundred trillion synapses,

    記住,老年痴呆症發作的根本原因

  • which is fantastic; we've got a lot to work with.

    就是突觸已經被破壞了。

  • And this isn't a static number.

    大腦平均擁有超過百萬億個突觸,

  • We gain and lose synapses all the time,

    這很奇妙;我們要處理 這麼龐大的數目。

  • through a process called neural plasticity.

    而這不是一個不變的數目。

  • Every time we learn something new,

    我們的突觸數目隨時都在增減,

  • we are creating and strengthening new neural connections,

    透過一個叫做 「神經可塑性」的過程。

  • new synapses.

    每當我們學到新東西,

  • In the Nun Study,

    我們就會創造和強化新的神經連結,

  • 678 nuns, all over the age of 75 when the study began,

    和新的突觸。

  • were followed for more than two decades.

    在我們以修女為研究對象 進行的研究當中,

  • They were regularly given physical checkups and cognitive tests,

    實驗開始時,678 位 全超過 75 歲的修女,

  • and when they died, their brains were all donated for autopsy.

    將會被追蹤調查超過 20 年。

  • In some of these brains, scientists discovered something surprising.

    她們會定期接受 健康檢查和認知測試,

  • Despite the presence of plaques and tangles and brain shrinkage --

    當她們死後,她們的大腦 會捐贈出來做病理解剖。

  • what appeared to be unquestionable Alzheimer's --

    科學家們在其中一些大腦中 發現了不可思議的東西。

  • the nuns who had belonged to these brains showed no signs

    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,

  • of having the disease while they were alive.

    這很明顯的,根本就是 阿茲海默症的典型病狀,

  • How can this be?

    但擁有這些大腦的修女, 她們在世時,

  • We think it's because these nuns had a high level of cognitive reserve,

    卻沒有表現出阿茲海默症的症狀。

  • which is a way of saying that they had more functional synapses.

    怎麼會這樣?

  • People who have more years of formal education,

    我們認為那是因為這些修女 擁有高度的認知儲備量,

  • who have a high degree of literacy,

    也就是說他們有較多 運作良好的突觸。

  • who engage regularly in mentally stimulating activities,

    接受正規教育較多年的人、

  • all have more cognitive reserve.

    擁有較高學歷的人、

  • They have an abundance and a redundancy in neural connections.

    和會定期參與 促進精神刺激活動的人,

  • So even if they have a disease like Alzheimer's

    都會有較多的認知儲備量。

  • compromising some of their synapses,

    他們有充裕的神經連結。

  • they've got many extra backup connections,

    所以即使他們因為患有像 阿茲海默那樣的疾病,

  • and this buffers them from noticing that anything is amiss.

    使她們減少了一些突觸,

  • Let's imagine a simplified example.

    她們還有很多備用的連結,

  • Let's say you only know one thing about a subject.

    從而減緩她們的大腦產生混亂。

  • Let's say it's about me.

    讓我們假想一個簡單的例子。

  • You know that Lisa Genova wrote "Still Alice,"

    假設你對一個主題只有一個認知。

  • and that's the only thing you know about me.

    假設那個主題就是我。

  • You have that single neural connection,

    你知道麗莎.吉諾瓦寫了一本 《我想念我自己》,

  • that one synapse.

    而這是你對我唯一的認知。

  • Now imagine you have Alzheimer's.

    你對我的認知, 只有單一個神經連結,

  • You have plaques and tangles and inflammation

    單一個突觸。

  • and microglia devouring that synapse.

    現在假設你有阿茲海默症。

  • Now when someone asks you, "Hey, who wrote 'Still Alice?'"

    你有澱粉樣蛋白斑、 神經纏結和發炎的情況,

  • you can't remember,

    你的微膠細胞吞噬了突觸。

  • because that synapse is either failing or gone.

    現在當有人問你, 「嘿,誰寫了《我想念我自己》?」

  • You've forgotten me forever.

    你不記得了,

  • But what if you had learned more about me?

    因為那個突觸不是失效就是不見了,

  • Let's say you learned four things about me.

    你就會永遠忘記我。

  • Now imagine you have Alzheimer's,

    但假如你對我了解更深呢?

  • and three of those synapses are damaged or destroyed.

    比如,你了解我四件事情。

  • You still have a way to detour the wreckage.

    現在想像一下,你得了阿茲海默症,

  • You can still remember my name.

    其中三個突觸被破壞了。

  • So we can be resilient to the presence of Alzheimer's pathology

    你仍有一條可以繞過那些 被破壞的突觸的路線。

  • through the recruitment of yet-undamaged pathways.

    你仍能記得我的名字。