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

翻译人员: Haoliang Chen 校对人员: Conway Ye

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

在座有多少人希望能活到八十岁以上？

Yeah.

好。

I think we all have this hopeful expectation

我想我们每个人

都渴望能够长寿。

of living into old age.

Let's project out into the future,

让我们穿越到未来，

to your future "you's,"

未来的你们

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

假设都已85岁。

Now, everyone look at two people.

我们随便挑选两个人，

One of you probably has Alzheimer's disease.

其中一人就可能患有老年痴呆症。

(Laughter)

（笑声）

Alright, alright.

好吧，好吧。

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

也许你会想：“反正不会是我”。

Then, OK. You are a caregiver.

那么好的。你是另一位的照顾人。

So --

所以……

(Laughter)

（笑声）

so in some way,

所以某种意义上来说，

this terrifying disease is likely to affect us all.

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

对于老年痴呆的恐惧部分源于

that there's nothing we can do about it.

我们对此的无能为力。

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

尽管几十年的研究下来，

我们依然没有改善病情的方法。

and no cure.

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

如果我们有幸长命百岁，

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

老年痴呆似乎是我们大脑的宿命。

But maybe it doesn't have to be.

情况也许没有这么糟。

What if I told you we could change these statistics,

如果我告诉你，我们可以改变现状，

literally change our brain's destiny,

就是改变我们大脑的命运，

without relying on a cure or advancements in medicine?

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

让我们先看看目前

about the neuroscience of Alzheimer's.

神经学上对老年痴呆的了解。

Here's a picture of two neurons connecting.

这是一张两个神经元连接的图。

The point of connection, this space circled in red,

连接的部位，也就是红色圈出的这块，

is called the synapse.

叫做突触。

The synapse is where neurotransmitters are released.

突触是神经递质释放的场所，

This is where signals are transmitted, where communication happens.

这是信号传送、交流的场所。

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

这是我们思考、感受、视听、欲望

and remember.

和记忆的场所。

And the synapse is where Alzheimer's happens.

而突触也正是老年痴呆发病的地方。

Let's zoom in on the synapse

让我们把突触放大，

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

看一则动画演示。

During the business of communicating information,

在信息沟通的过程中，

in addition to releasing neurotransmitters like glutamate into the synapse,

除了释放谷氨酸等神经递质到突触，

neurons also release a small peptide called amyloid beta.

神经元还释放了一种 名为β淀粉样蛋白的小肽。

Normally, amyloid beta is cleared away metabolized by microglia,

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。

the janitor cells of our brains.

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

尽管分子层面引发 老年痴呆的原因还争论不休，

most neuroscientists believe that the disease begins

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。

when amyloid beta begins to accumulate.

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

释放了太多，或者是未能完全清理，

and the synapse begins to pile up with amyloid beta.

突触因此便开始堆积β淀粉样蛋白。

And when this happens, it binds to itself,

若这一事件发生 突触逐渐束缚了自己，

forming sticky aggregates called amyloid plaques.

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?

在座的有多少人已经四十多岁了？

You're afraid to admit it now.

你不想承认了吗？

This initial step into the disease,

老年痴呆症的起步，

this presence of amyloid plaques accumulating,

淀粉样斑块的累积，

can already be found in your brains.

也许已经在你的大脑初步产生。

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

我们唯一能确认的方式是PET扫描，

because at this point, you are blissfully unaware.

因为现在你对此毫无知觉。

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

你还没有任何记忆、 语言、或是认知方面的问题...

yet.

现在还没有。

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

我们认为淀粉样斑块的累积 至少需要15至20年时间

before it reaches a tipping point,

才会到达它的临界点，

then triggering a molecular cascade

随后引发分子的连锁反应

that causes the clinical symptoms of the disease.

导致了这一疾病的临床症状。

Prior to the tipping point,

在这一临界点之前，

your lapses in memory might include things like,

你的记忆衰退可能会像这样：

"Why did I come in this room?"

“我为什么到这间屋子来？”

or "Oh ... what's his name?"

或是“呃，他叫什么来着？”

or "Where did I put my keys?"

或是“我把钥匙放哪了？”

Now, before you all start freaking out again,

现在，在你们惊慌失措之前，

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

我知道你们中的半数在过去的 24小时内至少有过上述之一，

these are all normal kinds of forgetting.

这些都是正常的遗忘类型。

In fact, I would argue that these examples

实际上，我的看法是这些示例，

might not even involve your memory,

甚至都与你的记忆没什么关系，

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

因为起初你并没有在意 你把钥匙放在哪里。

in the first place.

After the tipping point,

在临界点之后，

the glitches in memory, language and cognition are different.

记忆、语言和认知的偏差是不一样的。

Instead of eventually finding your keys in your coat pocket

最后发现钥匙并不在你的大衣口袋，

or on the table by the door,

或是不在门边的桌上，

you find them in the refrigerator,

你在冰箱里找到了你的钥匙，

or you find them and you think,

或者你找到钥匙后想，

"What are these for?"

“这玩意是干嘛的？”

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

所以当淀粉样斑块积累到 临界点后会发生什么？

Our microglia janitor cells become hyper-activated,

我们的看护细胞小神经 胶质细胞变得过度活跃，

releasing chemicals that cause inflammation and cellular damage.

释放出导致炎症和 细胞损伤的化学物质。

We think they might actually start clearing away

我们认为这可能会

清除突触本身。

the synapses themselves.

A crucial neural transport protein called "tau" becomes hyperphosphorylated

一种叫做tau蛋白的神经 转运蛋白变得过度磷酸化

and twists itself into something called "tangles,"

并转化成叫做神经纤维缠结的物质，

which choke off the neurons from the inside.

从内部阻塞了神经元。

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

在老年痴呆症的中期， 大量的炎症和神经纤维缠结

and all-out war at the synapse

以及突触处的全面战争

and cell death.

以及细胞的凋亡。

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

如果你是一位想要 治愈该病的科学家，

at what point would you ideally want to intervene?

最佳介入时机是什么时候呢？

Many scientists are betting big on the simplest solution:

许多科学家赌在了 最简单的解决方法上：

keep amyloid plaques from reaching that tipping point,

避免淀粉样斑块达到临界点，

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

也就意味着药物研发 很大程度上聚焦于

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

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。

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

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。

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

我们需要在临界点到达之前，

before the cascade is triggered,

在连锁反应产生之前，

before we start leaving our keys in the refrigerator.

在我们把钥匙落在冰箱前 服用这种药物。

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

我们认为这也是迄今为止 这类药物在临床试验上

in clinical trials --

失败的原因。

not because the science wasn't sound,

并不是因为科学技术不够可靠，

but because the people in these trials were already symptomatic.

而是因为在临床试验的人们 都已是老年痴呆的患者。

It was too late.

这就为时已晚。

Think of amyloid plaques as a lit match.

试想淀粉样斑块是已经点燃的火柴。

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

在临界点后，火柴的火引燃了整片森林。

Once the forest is ablaze,

一旦森林起火，

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

吹灭火柴早已于事无补。

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

你需要在火柴引燃 森林前就把火柴熄灭。

Even before scientists sort this out,

即使科学家还尚未解决问题，

this information is actually really good news for us,

这一好消息确实振奋人心，

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

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。

of amyloid plaques.

And so there are things we can do

我们可以做许多小事

to keep us from reaching that tipping point.

来避免达到临界点。

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

不妨把患老年痴呆的风险比作天平。

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

把可能增加风险的因素放在一端，

and when that arm hits the floor, you are symptomatic

如果一端触到地面，那么你将患病。

and diagnosed with Alzheimer's.

并被诊断为老年痴呆。

Let's imagine you're 50 years old.

假设你已五十岁。

You're not a spring chicken anymore,

你已不再年轻，

so you've accumulated some amyloid plaques with age.

随年岁增长你已积累了部分淀粉样斑块。

Your scale is tipped a little bit.

你的天平已经微微倾斜。

Now let's look at your DNA.

现在观察一下你的DNA。

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

我们的基因全部遗传自我们的父母。

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

一些基因会增加风险 还有一些会降低风险。

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

如果你像《依然爱丽丝》中的爱丽丝一样，

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

你遗传的一种罕见的基因突变， 粗制滥造着β淀粉样蛋白，

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

单单这一点就会使你的天平一端着地。

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

不过对于大多数人而言 该基因只会使天平稍稍倾斜。

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

举个例子，APOE4是一种 增加淀粉样蛋白的变异基因，

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

你可能会从父母那里 遗传一份APOE4的基因

and still never get Alzheimer's,

不过却不会患上老年痴呆，

which means that for most of us,

这也就意味着对大多数人而言，

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

我们的DNA并不是决定 老年痴呆的唯一要素。

So what does?

那么什么决定呢？

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

我们对于衰老无能为力 也无法决定我们遗传的基因。

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

到现在我们还没有 改变我们大脑的宿命。

What about sleep?

关于睡眠呢？

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

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，

throughout our brains,

clearing away metabolic waste that accumulated in our synapses

清除掉积累在突触的代谢废物

while we were awake.

当我们清醒时。

Deep sleep is like a power cleanse for the brain.

深度睡眠就好像是大脑的强效净化。

But what happens if you shortchange yourself on sleep?

那么如果你在睡眠方面亏待了自己呢？

Many scientists believe

许多科学家坚信

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

不良的睡眠卫生可能 是老年痴呆的前兆。

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

缺乏仅仅一晚的睡眠就会 增加β淀粉样蛋白。

And amyloid accumulation has been shown to disrupt sleep,

而淀粉样蛋白的累积 已被证实会影响睡眠，

which in turn causes more amyloid to accumulate.

从而导致了更多淀粉样蛋白的累积。

And so now we have this positive feedback loop

所以现在我们有了正反馈循环，

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

将会加剧天平的倾倒。

What else?

还有别的吗？

Cardiovascular health.

心血管的健康。

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

高血压、糖尿病、肥胖、 吸烟、高胆固醇，

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

这些都证明会增加患老年痴呆的风险。

Some autopsy studies have shown

一些验尸报告表明

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

有80%的老年痴呆患者

also had cardiovascular disease.

同样患有心血管疾病。

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

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。

in animal models of the disease.

So a heart-healthy Mediterranean lifestyle and diet

所以有益心脏健康的 地中海式生活方式和饮食

can help to counter the tipping of this scale.

可以有效扳回倾斜的天平。

So there are many things we can do

所以我们能做很多事

to prevent or delay the onset of Alzheimer's.

来预防或者延缓老年痴呆症的到来。

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

不过假设你并没有做任何事。

Let's say you're 65;

并且你已经六十五岁了，

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

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，

that tips your scale arm a bit;

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

你的生命之火渐渐微弱，

you love bacon;

你喜欢培根，

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

除非有人追你你懒得跑动。

(Laughter)

（笑声）

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

假设你的淀粉样斑块已经达到临界点。

Your scale arm has crashed to the floor.

你天平的一端已坠地。

You've tripped the cascade,

你触发了连锁反应，

setting fire to the forest,

引发了森林火灾，

causing inflammation, tangles, and cell death.

导致了炎症、神经纤维 缠结以及细胞凋亡。

You should be symptomatic for Alzheimer's.

你表现出老年痴呆的症状。

You should be having trouble finding words and keys

你在措辞和找钥匙时会碰到麻烦

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

并且回想不起我一开始讲的内容。

But you might not be.

也许你不会这样。

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

另外还有一件事可以帮助你

from experiencing the symptoms of Alzheimer's,

免于老年痴呆的症状，

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

哪怕你的大脑已病入膏肓。

It has to do with neural plasticity and cognitive reserve.

它需解决神经可塑性 和认知储备问题。

Remember, the experience of having Alzheimer's

记住，老年痴呆症的发作

is ultimately a result of losing synapses.

是突触损失的最终后果。

The average brain has over a hundred trillion synapses,

一般大脑有超过万亿的突触，

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

这很不可思议， 我们有这么庞大的数量。

And this isn't a static number.

而这一数字不是一成不变。

We gain and lose synapses all the time,

我们在一个叫做神经可塑性的过程之中，

through a process called neural plasticity.

不断生成和消耗着突触。

Every time we learn something new,

每当我们习得新东西，

we are creating and strengthening new neural connections,

我们建立并强化新的神经连接，

new synapses.

新的突触产生了。

In the Nun Study,

在Nun研究中，

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

研究开始时，678位修女全都年过七十五岁，

were followed for more than two decades.

进行了二十多年的研究。

They were regularly given physical checkups and cognitive tests,

她们会定期接受身体检查和认知测试，

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

如果不行去世，她们的大脑 都捐献出去用于验尸。

In some of these brains, scientists discovered something surprising.

科学家们在一些大脑中 发现了一些神奇的东西。

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

尽管样斑块、神经纤维 缠结和大脑的萎缩，

what appeared to be unquestionable Alzheimer's --

这些现象似乎是老年痴呆症无疑，

the nuns who had belonged to these brains showed no signs

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。

of having the disease while they were alive.

How can this be?

这是怎么回事呢？

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

我们认为这是因为这些 修女拥有高级的认知储备，

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

意味着她们有功能更强的突触。

People who have more years of formal education,

接受正式教育的时间越长的人，

who have a high degree of literacy,

拥有较强读写能力的人，

who engage regularly in mentally stimulating activities,

定期参加刺激心理活动的人，

all have more cognitive reserve.

这些人都有更高的认知储备。

They have an abundance and a redundancy in neural connections.

他们有着大量甚至多余的神经连接。

So even if they have a disease like Alzheimer's

所以即使他们患上老年痴呆等疾病

compromising some of their synapses,

损伤了部分突触，

they've got many extra backup connections,

他们依然有充足的额外后备连接，

and this buffers them from noticing that anything is amiss.

而这减缓了他们的大脑产生混乱。

Let's imagine a simplified example.

让我们来看一个简单的例子。

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

假设你只知道关于某一主题的一件事。

Let's say it's about me.

比方说是关于我的。

You know that Lisa Genova wrote "Still Alice,"

你知道丽莎·吉诺瓦 写下了《依然爱丽丝》，

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

这是你唯一知道的关于我的事。

You have that single neural connection,

你拥有一处单一的神经连接，

that one synapse.

那一个特定突触。

Now imagine you have Alzheimer's.

如果现在你患上了老年痴呆。

You have plaques and tangles and inflammation

你有样斑块、神经纤维缠结和炎症

and microglia devouring that synapse.

以及小神经胶质细胞吞噬了那一突触。

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

现在若有人问起你 “嘿，谁写了《依然爱丽丝》？“

you can't remember,

你无法回想起来了，

because that synapse is either failing or gone.

因为那个突触要么衰弱要么消失了。

You've forgotten me forever.

你把我忘得一干二净。

But what if you had learned more about me?

但是如果你对我了解更深呢？

Let's say you learned four things about me.

比如你了解我的四件事情。

Now imagine you have Alzheimer's,

现在如果你患上了老年痴呆，

and three of those synapses are damaged or destroyed.

即使三处突触已损伤或者毁坏。

You still have a way to detour the wreckage.

你依然有一条路来 绕过阻碍找到我的信息。

You can still remember my name.

你依然记得我的名字。

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

所以我们可以通过使用那些未损坏的通路

through the recruitment of yet-undamaged pathways.

有效应对老年痴呆。

And we create these pathways, this cognitive reserve,

同时我们通过学习新事物，

by learning new things.

创造了新的通路，改变着认知储备。

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

理想情况下，我们希望 这些新事物的意义尽可能丰富，

recruiting sight and sound and associations and emotion.

吸纳视觉与听觉的联合感受。

So this really doesn't mean doing crossword puzzles.

所以这并不意味着 去做横纵字谜游戏。

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

你不希望去重拾 那些你早已学会的信息，

because this is like traveling down old, familiar streets,

这就好比游览老旧的熟悉街道，

cruising neighborhoods you already know.

那些周边环境你早已了然于心。

You want to pave new neural roads.

你想要开辟新的神经道路。

Building an Alzheimer's-resistant brain

使你的大脑抵抗老年痴呆

means learning to speak Italian,

意味着学习说意大利语，

meeting new friends,

去遇见新朋友，

reading a book,

读一本书，

or listening to a great TED Talk.

或是听一场精彩的TED演讲。

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

如果做了所有的这一切之后 有一天你被诊断为老年痴呆，

there are three lessons I've learned from my grandmother

我从我的祖母以及我认识的许多患者中

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

学习到了三件事情。

Diagnosis doesn't mean you're dying tomorrow.

诊断并不意味着死期将至。

Keep living.

顽强地活下去吧。

You won't lose your emotional memory.

你不会丢失你的情感记忆。

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

你依然可以理解爱与喜悦。

You might not remember what I said five minutes ago,

你也许不会记得我五分钟前的话语，

but you'll remember how I made you feel.

但是你依然会记得我带给你的感受。

And you are more than what you can remember.

你远胜于你所能记住的一切。

Thank you.

谢谢。

(Applause)

（掌声）