Name: 如何減緩認知能力衰退 | 彼得-阿蒂亞博士和安德魯-休伯曼博士 (How to Slow Cognitive Decline | Dr. Peter Attia & Dr. Andrew Huberman)
Uploaded: 2024-11-28T07:12:44.000Z
Duration: 15 min 29 s

What is the story with neurodegenerative disease, Alzheimer's in particular?

神經退行性疾病，尤其是阿爾茨海默氏症是怎麼回事？

情態副詞

And perhaps as importantly, how can we all slow our own cognitive decline irrespective of whether or not we get what is called Alzheimer's dementia?

也許同樣重要的是，無論我們是否會患上所謂的阿爾茨海默氏痴呆症，我們如何才能減緩自己認知能力的衰退？

So Alzheimer's disease is both the most prevalent form of dementia and the most prevalent neurodegenerative disease.

是以，阿爾茨海默病既是最常見的痴呆症，也是最常見的神經退行性疾病。

是以，它佔據了這個獨特的位置。

We're talking about roughly 6 million people in the United States have Alzheimer's disease.

在美國，大約有 600 萬人患有阿爾茨海默病。

That's one in, let's see, I mean, about 2% of the total population.

讓我們來看看，我的意思是，約佔總人口的 2%。

But that doesn't include those with mild cognitive impairment or pre-dementia or other forms of dementia.

但這並不包括那些患有輕度認知障礙、痴呆前期或其他形式痴呆症的人。

And of course, the right metric is not what percent of the population, which of course includes children, things like that.

當然，正確的衡量標準不是人口的百分比，其中當然包括兒童等。

So is age the major risk factor for getting Alzheimer's?  We stay with glaucoma, a disease I'm much more familiar with because my lab worked on it for many years.

那麼，年齡是患老年痴呆症的主要風險因素嗎？  我們繼續討論青光眼，我對這種疾病更為熟悉，因為我的實驗室多年來一直在研究這種疾病。

The biggest risk factor for getting glaucoma is age.

患青光眼的最大風險因素是年齡。

The greatest risk factor for cardiovascular disease is age.

心血管疾病的最大風險因素是年齡。

The greatest risk factor for cancer is age.

We tend to not spend a lot of time talking about that because it's not a modifiable risk.

我們往往不會花很多時間討論這個問題，因為這不是一個可改變的風險。

So, you know, we tend to focus on modifiable risk factors.

是以，我們傾向於關注可改變的風險因素。

So what else can we tell you just to give you kind of lay of the land?

那麼，我們還能告訴你什麼呢？

So the second most prevalent neurodegenerative disease would probably be Lewy body dementia followed by Parkinson's disease, although the rate of growth of Parkinson's disease is the highest.

是以，第二大流行的神經退行性疾病可能是路易體痴呆，其次是帕金森病，儘管帕金森病的增長率最高。

So I think it would probably be most, you know, those three diseases we want to really be paying a lot of attention to.

是以，我認為我們最應該關注的可能就是這三種疾病。

As you know, there are a lot of other neurodegenerative diseases.

大家都知道，還有很多其他的神經退行性疾病。

Every one of these things is devastating.

Like multiple sclerosis.  Multiple sclerosis, ALS, Huntington's disease.

比如多發性硬化症  多發性硬化症、漸凍人症、亨廷頓氏病。

Vascular dementia is not Alzheimer's dementia, but it produces comparable symptoms.

血管性痴呆不是阿爾茨海默氏痴呆，但它會產生類似的症狀。

Each of these things, by the way, are slightly different.

順便說一句，這些事情各有不同。

It's a dementing disease, but it also has a movement component.

這是一種痴呆症，但也有運動的成分。

So it sort of sits on a spectrum that's sort of, you know, I mean, loosely halfway between Alzheimer's disease and Parkinson's disease.

是以，它是一種介於阿爾茨海默病和帕金森病之間的疾病。

We talked obviously about age being the number one risk factor.

我們顯然談到了年齡是頭號風險因素。

Kind of not that interesting because you can't do anything about it.

沒那麼有趣，因為你對此無能為力。

So the real goal is as we age, what are we doing to reduce risk?

是以，真正的目標是，隨著年齡的增長，我們該如何降低風險？

Well, let's start with an important gene.

那麼，讓我們從一個重要的基因開始吧。

The gene that everybody's heard of certainly came up a lot on the Limitless special where Chris Hemsworth was, you know, made the decision to reveal something that none of us expected when we started that whole series, which was that he ended up being homozygous for the ApoE4 isoform.

克里斯-海姆斯沃斯（Chris Hemsworth）在《無極限》（Limitless）特輯中透露了一個大家都聽說過的基因，那就是他是載脂蛋白E4異構體的同卵雙生型。

So maybe folks understand we have two copies of every gene.

所以，也許人們會明白，我們的每個基因都有兩個拷貝。

So for gene X, you have copy that you got from your mom and copy that you got from your dad.

是以，對於 X 基因，你有從母親那裡得到的拷貝，也有從父親那裡得到的拷貝。

And the ApoE gene is kind of a unique gene in that it really, it has three different isoforms that are all considered normal.

載脂蛋白 E 基因是一種獨特的基因，它有三種不同的異構體，但都被認為是正常的。

So you have the E2 isoform, the E3 isoform, and the E4 isoform.

是以有 E2 異構體、E3 異構體和 E4 異構體。

That's the one that we have historically had as far back as we can go.

從歷史上看，我們一直都是這樣做的。

We actually think the E4 isoform offered a lot of advantages back in the day.

實際上，我們認為 E4 異構體在當時具有很多優勢。

It's a bit of a pro-inflammatory isoform and it certainly offered protection against infections, especially parasitic infections in the CNS, which would have been a really important thing to select for 200,000 years ago.

它有點像促發炎同工酶，肯定能抵禦感染，尤其是中樞神經系統的寄生蟲感染，這在 20 萬年前是非常重要的選擇。

寄生蟲如何進入中樞神經系統？

I mean, you have a blood-brain barrier, you have a thick skull.

我是說，你有血腦屏障，你有厚厚的頭骨。

I mean, I'm not calling, I'm not telling you you have a thick skull, but, but I mean, it just seems like parasites and other tissues would be an issue because what we're talking about here is brain disease.

我的意思是，我不是說你的頭骨很厚，但我的意思是，寄生蟲和其他組織似乎是一個問題，因為我們在這裡談論的是腦部疾病。

Anyway, I don't want to take us off course.

總之，我不想讓我們偏離正軌。

It probably offered some protection outside of the brain as well.

它或許還能在大腦之外提供一些保護。

Anyway, the, the E3 isoform I think showed up, God, I think 50,000 years ago.

總之，E3異構體我認為是在5萬年前出現的。

And the E2 isoform showed up very recently, about 10,000 years ago.

而 E2 異構體出現的時間很短，大約在 1 萬年前。

Now, today we realize that there's a clear stratification of risk when it comes to Alzheimer's disease that tracks with those isoforms.

如今，我們意識到，阿爾茨海默病的風險分層與這些同工酶密切相關。

So because you have two copies, you basically have six combinations of how you can combine those genes.

是以，由於你有兩個拷貝，你基本上可以有六種組合來組合這些基因。

You could be 2-2, 2-3, 2-4, 3-3, 3-4, 4-4.

你可能是 2-2、2-3、2-4、3-3、3-4、4-4。

The prevalence of them is basically as follows. 3-3 is now the most common. 3 is the most common.

它們的流行情況基本如下。3-3 現在是最常見的。3 是最常見的。

So double 3 is 55-ish percent of the population.

是以，雙 3 佔總人口的 55%左右。

The next most common is the 3-4, which is about 25% of the population.

其次是 3-4 歲，約佔總人口的 25%。

And then after that, most things are kind of a rounding error.

在此之後，大多數事情都是四捨五入的誤差。

So 2-3s and 2-4s would be the next most common. 4-4s are very rare.

是以，2-3 級和 2-4 級是其次最常見的。4-4非常罕見。

And 2-2s are the rarest of them all. 2-2s are less than 1%. 4-4s are about 1-2%.

而 2-2 是最罕見的。2-2 的比例不到 1%。4-4 約為 1-2%。

Very important point here is that the E4 genes are not deterministic.

這裡非常重要的一點是，E4 基因不是決定性的。

So they're highly associated with the risk, but they're not deterministic.

是以，它們與風險高度相關，但並不是決定性的。

There are at least three deterministic genes in Alzheimer's disease.

阿爾茨海默病至少有三種決定性基因。

One is called PSEN1, another one is called PSEN2, and another one is called APP.

一個叫 PSEN1，另一個叫 PSEN2，還有一個叫 APP。

Those genes collectively make up about 1% of cases of people with Alzheimer's disease.

在阿爾茨海默氏症患者中，這些基因合計約佔 1%。

So they're fortunately very rare genes, but sadly they are deterministic.

是以，幸運的是，它們是非常罕見的基因，但不幸的是，它們是決定性的。

Meaning if you have those genes, you do get Alzheimer's disease.

也就是說，如果你有這些基因，你就會得阿爾茨海默病。

And what's perhaps most devastating about those genes is how early the onset is of the disease.

而這些基因最具破壞性的地方，或許就在於其發病的早期性。

These are people that are usually getting Alzheimer's disease in their 50s.

這些人通常在 50 多歲時就會患上老年痴呆症。

所以，我們的診所裡確實有一個病人。

Actually, she's spoken about this very openly, whose mom had one of these genes.

事實上，她曾公開談論過這個問題，她的媽媽也有這樣的基因。

And she got Alzheimer's disease in her early 50s.

她在 50 歲出頭時得了老年痴呆症。

I think she might have made it into her 60s before she died.

我想她可能活到 60 多歲才去世。

But absolutely devastating consequences here.

阿爾茨海默氏症患者為什麼會死亡？

Because I know about the hippocampal degeneration.

因為我知道海馬體退化的情況。

Hippocampus, of course, being an area of the brain important for learning and memory.

當然，海馬體是大腦中對學習和記憶非常重要的區域。

Do they lose breathing centers or cardiovascular control?

他們會失去呼吸中樞或心血管控制嗎？

Usually what happens is it's sort of failure to thrive, aspiration, things like that.

通常情況下，會出現發育不全、抽風之類的症狀。

So it's usually they just stop eating or they can't control secretions.

是以，他們通常會停止進食或無法控制分泌物。

Or they really lose the ability to even sense pain in their body.

或者，他們真的失去了感知身體疼痛的能力。

And therefore they'll get an ulcer and they don't realize it.

是以，他們會得潰瘍，卻不自知。

And it'll become cellulitic and they'll develop a horrible infection in response to it.

然後就會變成蜂窩組織，並引發可怕的感染。

The reason I ask is every once in a while a news report will come out based on a legitimate case study where they'll do a scan on some person and discover that they're missing literally half their cerebral cortex.

我問這個問題的原因是，每隔一段時間就會有新聞報道，根據一個合法的案例研究，他們會對某個人進行掃描，發現他們的大腦皮層實際上缺失了一半。

Like huge chunks of brain and they're functioning relatively normally.

就像大塊大塊的大腦，它們的功能相對正常。

And so here we're talking about a neurodegenerative disease of relatively, it's widespread but there are a few hot spots, of course, in the brain that degenerate more profoundly than others and the people dying.

是以，我們在這裡討論的是一種神經退行性疾病，這種疾病的發病範圍很廣，但在大腦中，當然有幾個熱點部位的退化程度比其他部位更深，而人們也會是以而死亡。

It extends to lack of peripheral awareness or control and then some acute injury or infection.

它延伸到缺乏周邊意識或控制，然後是一些急性損傷或感染。

You mentioned earlier some of the controversy, right?

你剛才提到了一些爭議，對嗎？

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