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,