What You Can Do to Prevent Alzheimer's | Lisa Genova | TED

譯者: Jean Liao 審譯者: 易帆 余

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

我們對阿茲海默症神經學上的了解。

about the neuroscience of Alzheimer's.

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

至少曾經經歷過 上述的其中一件事情，

these are all normal kinds of forgetting.

這些都是正常的遺忘症狀。

In fact, I would argue that these examples

事實上，上述這些例子

might not even involve your memory,

可能根本與你的記憶無關，

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

因為你第一時間，

並不會去注意到 你把鑰匙放到哪裡。

in the first place.

After the tipping point,

一旦臨界點發生之後，

the glitches in memory, language and cognition are different.

你的記憶、語言和認知上的偏差 就會變得不同了。

Instead of eventually finding your keys in your coat pocket

你最後才知道鑰匙 並非在你的外套口袋裡，

or on the table by the door,

也並非門旁的桌子上，

you find them in the refrigerator,

而是你把它放在冰箱裡了，

or you find them and you think,

或者，你找到它後，你卻在想：

"What are these for?"

「這東西是用來做甚麼用的？」

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

當澱粉樣蛋白斑累積到臨界點時， 到底會發生甚麼事？

Our microglia janitor cells become hyper-activated,

我們的微膠細胞清潔工 會變得極度活躍，

releasing chemicals that cause inflammation and cellular damage.

它們會釋放出化學物質， 造成發炎和細胞的損壞。

We think they might actually start clearing away

我們認為它們正在清除的

the synapses themselves.

就是突觸本身。

A crucial neural transport protein called "tau" becomes hyperphosphorylated

有一個重要的神經傳導蛋白叫做 「tau 蛋白」會被過磷酸化，

and twists itself into something called "tangles,"

並把自己轉變成一種叫 「纖維纏結」的東西，

which choke off the neurons from the inside.

從內部堵塞神經元。

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

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，

and all-out war at the synapse

and cell death.

然後細胞就會死亡。

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

假如你是科學家， 試著要治療這個疾病，

at what point would you ideally want to intervene?

最佳的介入時機是甚麼時候呢？

Many scientists are betting big on the simplest solution:

許多科學家賭在 最簡單的解決方案上：

keep amyloid plaques from reaching that tipping point,

避免澱粉樣蛋白斑累積到臨界點，

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

也就是說，大部分的 藥物治療主要是研究化合物

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

利用它們來預防、消除或減少 澱粉樣蛋白斑的累積。

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

所以他們研發的藥物， 都只是一些預防老年癡呆的藥物。

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

我們會在達到臨界點之前、

before the cascade is triggered,

在分子連鎖反應產生之前、

before we start leaving our keys in the refrigerator.

在我們開始把鑰匙 遺忘在冰箱裡之前服用這些藥物。

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

我們認為這是目前為止 這些藥物在臨床實驗中

in clinical trials --

失敗的原因……

not because the science wasn't sound,

並不是科學不夠可靠，

but because the people in these trials were already symptomatic.

而是因為實驗對象都已經有症狀了。

It was too late.

已經太遲了。

Think of amyloid plaques as a lit match.

試想澱粉樣蛋白斑 是一根已經點燃的火柴棒。

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

到了臨界點時，火柴棒點燃了森林。

Once the forest is ablaze,

一旦森林著火，

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

把火柴棒吹熄已於事無補。

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

你必須在森林著火之前就吹熄火柴。

Even before scientists sort this out,

即使科學家尚未找到解決方法，

this information is actually really good news for us,

但這個消息確實振奮人心，

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

因為它證明了我們生活的方式

會影響澱粉樣蛋白的累積。

of amyloid plaques.

And so there are things we can do

我們可以做一些事情，

to keep us from reaching that tipping point.

來避免自己達到臨界點。

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

讓我們把罹患老年癡呆的風險 比作是蹺蹺板。

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

我們把造成風險的因素 放在蹺蹺板的其中一邊，

and when that arm hits the floor, you are symptomatic

當這一邊碰到地面， 那麼症狀就會出現，

and diagnosed with Alzheimer's.

然後被診斷為阿茲海默症。

Let's imagine you're 50 years old.

假設你已經 50 歲。

You're not a spring chicken anymore,

你已不再年輕，

so you've accumulated some amyloid plaques with age.

隨著年紀增長，你已經 累積了一些澱粉狀蛋白班。

Your scale is tipped a little bit.

你的蹺蹺板已稍微傾斜。

Now let's look at your DNA.

現在我們來看看你的 DNA。

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

我們從父母那裡繼承了基因。

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

有些基因會增加風險而有些會減少。

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

如果你們像電影《我想念我自己》 中的女主角愛莉絲一樣，

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

遺傳了罕見的基因突變， 不正常地大量增生 β-類澱粉蛋白，

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

這會讓你的蹺蹺板一端墜落到地面，

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

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。

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

舉例來說，APOE4 是一個 會增生澱粉樣蛋白斑的變種基因，

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

但你可能從父母那裡 遺傳了 APOE4，

and still never get Alzheimer's,

卻不會得到阿茲海默症，

which means that for most of us,

也就是說對大多數人來說，

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

光憑我們的 DNA 並不能決定 我們是否會得阿茲海默症。

So what does?

那麼甚麼能決定呢？

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

我們對於衰老無能為力， 也無法決定我們遺傳的基因。

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

目前為止，我們仍無法改變 大腦的宿命。

What about sleep?

那麼睡覺呢？

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

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。

throughout our brains,

clearing away metabolic waste that accumulated in our synapses

當我們清醒的時候，

while we were awake.

它會清除掉累積在突觸的 代謝廢物。

Deep sleep is like a power cleanse for the brain.

深度睡眠就好像大腦的強效淨化。

But what happens if you shortchange yourself on sleep?

假如你稍微改變 睡眠方式會發生甚麼事？

Many scientists believe

許多科學家相信，

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

糟糕的睡眠狀況 可能會導致阿茲海默症。

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

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 amyloid accumulation has been shown to disrupt sleep,

而澱粉樣蛋白斑的累積 已被證實會干擾睡眠，

which in turn causes more amyloid to accumulate.

結果導致更多澱粉樣蛋白斑的累積。

And so now we have this positive feedback loop

成為一個惡性循環，

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

加劇了蹺蹺板的傾斜。

What else?

還有甚麼？

Cardiovascular health.

心血管健康。

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

高血壓、糖尿病、過重、 抽菸、高膽固醇，

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

全都會增加罹患阿茲海默症的風險。

Some autopsy studies have shown

病理剖析的研究報告顯示，

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

罹患阿茲海默的人群中， 多達 80% 的病患，

also had cardiovascular disease.

同時擁有心血管疾病。

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

許多阿茲海默症的 動物模擬實驗研究中顯示，

in animal models of the disease.

有氧運動可以減少 β-類澱粉蛋白的數量。

So a heart-healthy Mediterranean lifestyle and diet

所以有益身心健康的 地中海式生活飲食方式，

can help to counter the tipping of this scale.

可以幫忙抵抗蹺蹺板的傾斜。

So there are many things we can do

所以我們有很多事可以做，

to prevent or delay the onset of Alzheimer's.

來預防或延緩老年痴呆症的到來。

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

但假設你甚麼事都沒做。

Let's say you're 65;

假設你已 65 歲；

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

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，

that tips your scale arm a bit;

這會讓你的蹺蹺板傾斜一點點；

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

你已經蠟燭兩頭燒了好幾年；

you love bacon;

你愛吃培根；

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

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.

想像你的澱粉樣蛋白斑 已經累積到臨界點。

Your scale arm has crashed to the floor.

你的蹺蹺板已經墜落到地面。

You've tripped the cascade,

你觸發了連鎖反應，

setting fire to the forest,

引發了森林大火，

causing inflammation, tangles, and cell death.

你開始出現發炎、 神經纏結和細胞凋亡的情況。

You should be symptomatic for Alzheimer's.

你的阿茲海默症已經病發。

You should be having trouble finding words and keys

你開始會造詞困難、找不到鑰匙，

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

記不得我在演講剛開始時 到底說了些甚麼。

But you might not be.

但你也可能不會這樣。

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

你還可以做一件事來保護自己，

from experiencing the symptoms of Alzheimer's,

來避免阿茲海默症狀出現，

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

那怕你的大腦已病入膏肓，

It has to do with neural plasticity and cognitive reserve.

它仍然跟神經可塑性 和認知儲備有關。

Remember, the experience of having Alzheimer's

記住，老年痴呆症發作的根本原因

is ultimately a result of losing synapses.

就是突觸已經被破壞了。

The average brain has over a hundred trillion synapses,

大腦平均擁有超過百萬億個突觸，

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

這很奇妙；我們要處理 這麼龐大的數目。

And this isn't a static number.

而這不是一個不變的數目。

We gain and lose synapses all the time,

我們的突觸數目隨時都在增減，

through a process called neural plasticity.

透過一個叫做 「神經可塑性」的過程。

Every time we learn something new,

每當我們學到新東西，

we are creating and strengthening new neural connections,

我們就會創造和強化新的神經連結，

new synapses.

和新的突觸。

In the Nun Study,

在我們以修女為研究對象 進行的研究當中，

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

實驗開始時，678 位 全超過 75 歲的修女，

were followed for more than two decades.

將會被追蹤調查超過 20 年。

They were regularly given physical checkups and cognitive tests,

她們會定期接受 健康檢查和認知測試，

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

當她們死後，她們的大腦 會捐贈出來做病理解剖。

In some of these brains, scientists discovered something surprising.

科學家們在其中一些大腦中 發現了不可思議的東西。

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

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，

what appeared to be unquestionable Alzheimer's --

這很明顯的，根本就是 阿茲海默症的典型病狀，

the nuns who had belonged to these brains showed no signs

但擁有這些大腦的修女， 她們在世時，

of having the disease while they were alive.

卻沒有表現出阿茲海默症的症狀。

How can this be?

怎麼會這樣？

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

我們認為那是因為這些修女 擁有高度的認知儲備量，

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

也就是說他們有較多 運作良好的突觸。

People who have more years of formal education,

接受正規教育較多年的人、

who have a high degree of literacy,

擁有較高學歷的人、

who engage regularly in mentally stimulating activities,

和會定期參與 促進精神刺激活動的人，

all have more cognitive reserve.

都會有較多的認知儲備量。

They have an abundance and a redundancy in neural connections.

他們有充裕的神經連結。

So even if they have a disease like Alzheimer's

所以即使他們因為患有像 阿茲海默那樣的疾病，

compromising some of their synapses,

使她們減少了一些突觸，

they've got many extra backup connections,

她們還有很多備用的連結，

and this buffers them from noticing that anything is amiss.

從而減緩她們的大腦產生混亂。

Let's imagine a simplified example.

讓我們假想一個簡單的例子。

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

假設你對一個主題只有一個認知。

Let's say it's about me.

假設那個主題就是我。

You know that Lisa Genova wrote "Still Alice,"

你知道麗莎．吉諾瓦寫了一本 《我想念我自己》，

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

而這是你對我唯一的認知。

You have that single neural connection,

你對我的認知， 只有單一個神經連結，

that one synapse.

單一個突觸。

Now imagine you have Alzheimer's.

現在假設你有阿茲海默症。

You have plaques and tangles and inflammation

你有澱粉樣蛋白斑、 神經纏結和發炎的情況，

and microglia devouring that synapse.

你的微膠細胞吞噬了突觸。

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

現在當有人問你， 「嘿，誰寫了《我想念我自己》？」

you can't remember,

你不記得了，

because that synapse is either failing or gone.

因為那個突觸不是失效就是不見了，

You've forgotten me forever.

你就會永遠忘記我。

But what if you had learned more about me?

但假如你對我了解更深呢？

Let's say you learned four things about me.

比如，你了解我四件事情。

Now imagine you have Alzheimer's,

現在想像一下，你得了阿茲海默症，

and three of those synapses are damaged or destroyed.

其中三個突觸被破壞了。

You still have a way to detour the wreckage.

你仍有一條可以繞過那些 被破壞的突觸的路線。

You can still remember my name.

你仍能記得我的名字。

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

所以當我們有阿茲海默症的 病理狀況發生，

through the recruitment of yet-undamaged pathways.

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，

And we create these pathways, this cognitive reserve,

我們可以藉由學習新事物，

by learning new things.

創造出新的通路、 增加認知的儲備量。

Ideally, we want these new things to be as rich in meaning as possible,

理想上，我們希望這些新事物 越有豐富的意義越好，

recruiting sight and sound and associations and emotion.

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.

我的意思並非要你去做拼字遊戲。

You don't want to simply retrieve information you've already learned,

你不會想只是重拾你 已學習過的記憶，

because this is like traveling down old, familiar streets,

因為這就好比遊覽 老舊而熟悉的街頭，

cruising neighborhoods you already know.

那些周邊環境你已了然於心。

You want to pave new neural roads.

你要鋪設新的神經通路。

Building an Alzheimer's-resistant brain

建造一個能抵禦阿茲海默症的大腦，

means learning to speak Italian,

像是去學習義大利語、

meeting new friends,

去交新朋友、

reading a book,

讀一本書，

or listening to a great TED Talk.

或聆聽超讚的 TED 演講。

And if, despite all of this, you are someday diagnosed with Alzheimer's,

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，

there are three lessons I've learned from my grandmother

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。

and the dozens of people I've come to know living with this disease.

Diagnosis doesn't mean you're dying tomorrow.

被診斷出阿茲海默症 並不代表你明天就會死掉。

Keep living.

繼續活下去。

You won't lose your emotional memory.

你不會喪失你的情感記憶。

You'll still be able to understand love and joy.

你仍能理解愛與歡樂。

You might not remember what I said five minutes ago,

你可能不會記得 五分鐘前我說了甚麼，

but you'll remember how I made you feel.

但你會記得我讓你感受到了甚麼。

And you are more than what you can remember.

你本身，比你能記得的 東西更有意義。

Thank you.

謝謝。

(Applause)

（掌聲）