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什么是脑雾？
What is brain fog?
那我们来澄清一下。
So let's like clear it up.
也就是说，什么是脑雾？
Like, what is brain fog?
也就是说，人们什么时候
Like, when should someone
应该担心？
be worried?
是的。
Yeah.
这正是脑科学家开始将更年期视为阿尔茨海默病风险因素的原因之一。
It's one of the reasons that actually brain scientists started to look into menopause as a risk factor for Alzheimer's disease.
直到今天，来到我们在威尔康奈尔医学学院、纽约长老会医院所运营的阿尔茨海默病预防诊所的绝大多数患者，都是因为中年时期出现的脑雾——这种脑雾严重到足以引发人们对早发性痴呆的担忧。
And still today, the vast majority of patients who come to us at Alzheimer's Prevention Clinic at Weill Cornell Medicine, New York Presbyterian, which I run, come to us because because of brain fog in midlife that can be so severe to really trigger concerns about early onset dementia.
因此，明确什么是脑雾、什么是阿尔茨海默病，以及前者如何引发对后者的担忧非常重要，因为这种恐惧确实是合理的。
So, it's really important to clarify what is brain fog and what is Alzheimer's and how one thing could lead to concerns about the others because it's really legitimate to be scared.
在UNPAUSED节目中表达的观点和意见仅属于嘉宾本人，仅供信息和娱乐目的。
The views and opinions expressed on unPAUSED are those of the talent and guests alone and are provided for informational and entertainment purposes only.
本播客或任何相关材料均不构成专业医疗建议、诊断或治疗的替代。
No part of this podcast or any related materials are intended to be a substitute for professional medical advice, diagnosis, or treatment.
当我第一次听到丽莎·莫斯科尼医生说的时候。
When I first heard Doctor.
丽莎·莫斯科尼医生展示了女性从绝经前期到绝经后期的大脑影像。
Lisa Mosconi speak, she showed brain imaging that followed a woman from premenopause into postmenopause.
这些变化清晰而不可否认。
The changes were distinct and undeniable.
我们真的会在绝经期间重新塑造大脑。
We literally rewire our brains through menopause.
我记得当时震惊得说不出话来，因为在我的培训和临床实践中，从来没有人向我展示过这些。
I remember sitting there floored, because in my training and practice, no one had ever shown me this before.
看到女性大脑在扫描中经历转变，既令人欣慰，又改变了我的人生。
To see a woman's brain transition captured on a scan was both validating and life changing.
这证明了多年来我的许多患者告诉我的话：我再也感觉不到自己了。
It was proof of what so many of my patients had told me over the years: I just don't feel like myself anymore.
莫斯科尼医生。
Doctor.
莫斯科尼告诉我们，这不仅仅是一种感觉，而是生物学现象，必须认真对待。
Mosconi showed us that this isn't just a feeling, it's biology, and it needs to be taken seriously.
然后，我了解了她的个人经历。
And then I learned her personal story.
她从小目睹祖母和两位姑婆都患上了痴呆症，而她们的兄弟却没有。
She grew up watching her grandmother and two great aunts all develop dementia, while their brother did not.
这种令人心碎的模式成为了她一生的事业。
That heartbreaking pattern became her life's work.
她将悲痛转化为使命，提出了一个无人问及的问题：为什么三分之二的阿尔茨海默病患者是女性？绝经在其中扮演了什么角色？
She turned grief into purpose, asking the question no one else was asking: Why are two thirds of all Alzheimer's patients women, and what role does menopause play in that risk?
最让我印象深刻的是，医生。
What struck me the most is that Doctor.
莫斯科尼从未回避这些艰难的问题。
Mosconi has never shied away from those hard questions.
她挑战了忽视女性大脑的旧有教条，从而开启了一场关于女性健康的新对话。
She has pushed against the old dogma that ignored women's brains, and in doing so, she's opened up an entirely new conversation about women's health.
她让我们明白，更年期不仅仅是一个卵巢的故事，更是一个大脑的故事。
She's shown us that menopause is not just an ovarian story, it's a brain story.
医生。
Doctor.
丽莎·莫斯科尼博士是威尔康奈尔医学院、纽约长老会医院神经学和放射学领域的神经科学副教授。
Lisa Mosconi, PhD, is a neuroscientist and associate professor of neuroscience in neurology and radiology at Weill Cornell Medicine, New York Presbyterian Hospital.
她是阿尔茨海默病预防项目的主任，该项目包括由美国国立卫生研究院资助的女性大脑倡议、屡获殊荣的阿尔茨海默病预防诊所，以及新成立的阿尔茨海默病预防临床试验单位。
She is the Director of the Alzheimer's Prevention Program, which includes NIH funded Women's Brain Initiative, the award winning Alzheimer's Prevention Clinic, and the newly launched Alzheimer's Prevention Clinical Trials Unit.
最近，她被任命为一项价值五千万美元的女性健康项目——“通过内分泌学降低阿尔茨海默病风险”的主任，这是一个开创性的计划，将激素和中年置于痴呆预防的核心位置。
Most recently, she was named director of the $50,000,000 program in women's health, Cutting Alzheimer's Risk Through Endocrinology, a groundbreaking initiative placing hormones and midlife at the center of dementia prevention.
她还撰写了多本畅销书，包括《更年期大脑》。
She's also the author of a number of bestselling books, including The Menopause Brain.
我最钦佩的是，医生。
What I admire most is that Doctor.
莫斯康尼不仅推动了科学进步，还改变了公众的讨论方式。
Mosconi is not only advancing science, she's changing the conversation.
我是医生。
I'm Doctor.
玛丽·克莱尔·哈弗，一位获得认证的妇产科医生和更年期专业医师。
Mary Claire Haver, a board certified obstetrician and gynecologist and certified menopause practitioner.
我同时也是德克萨斯大学医学分部妇产科的兼职教授。
I'm also an adjunct professor of obstetrics and gynecology at the University of Texas Medical Branch.
欢迎收听《Unpaused》——这档播客旨在打破沉默，探讨女性在人生后半程真正走向繁荣所需的一切。
Welcome to Unpaused, the podcast where we cut through the silence and talk about what it really takes for women to thrive in the second half of life.
欢迎来到《Unpaused》。
So welcome to Unpaused.
谢谢您邀请我。
Thank you for having me.
很高兴终于请到您了。
I'm so glad that we got you.
所以
So
我们已经是很久的朋友了。
we have been friends for a long time.
我想说，我第一次见到你是在我举办的首届Well活动上，地点在圣莫尼卡。
I wanna say the first time I saw you was on stage at my first Well event in Santa Monica.
你站起来展示了一系列女性在绝经前期、围绝经期和绝经后期的大脑图像，以及葡萄糖摄取的差异和正在发生的变化。
And you stood up and started showing images of the brain of women in premenopause and perimenopause and postmenopause, and the differences in glucose uptake and what's happening.
我当时就坐在观众席上。
And I stood there in the audience.
那是在Avren Blooming和Carol刚刚拆解了WHI研究之前或之后。
It was before or after Avren Blooming and Carol had, like, dismantled the WHI.
那天我简直震惊了。
My mind was so blown that day.
然后你谈到女性在更年期期间大脑的变化，我当时就想：从来没人告诉过我这些。
And then you're talking about how women's brains change through menopause, and I'm like, no one ever told me this.
在我的整个培训过程中，从来没有人、从来没有、从来没有跟我提过结构性变化、生物学层面的改变，以及更年期其实是一个神经内分泌事件。
No one ever, ever, ever in all of my training talked to me about the structural changes and the biological and, you know, that menopause was a neuroendocrine event.
你为我打开了这扇门。
And you opened that door for me.
因此，我将永远感激自己对这一切的理解。
And so I'll forever be grateful in my understanding.
但让我们来谈谈我们的祖母们。
Back But So to let's talk about our grandmothers.
我们来聊聊这个。
Let's talk about that.
你和我有着类似的故事：我的祖母在九十多岁、快百岁时去世，她最后那段日子，我那时根本不知道该怎么称呼它。
You share a similar story to mine in that my grandmother who died in her early nineties, mid nineties, spent the last I didn't know what to call it back then.
当然，那时我刚上大学，可能刚开始学医。
Of course, I was in early college, maybe starting med school.
她最后卧床不起。
And she was bedridden at the end.
我现在知道她患有痴呆症，很可能是阿尔茨海默病，身体非常虚弱，最后两三年几乎一直躺在床上。
And I know now that she had dementia, likely Alzheimer's, and was very, very frail, and was probably the last two to three years in a bed.
她人很温柔，但后来变得非常困惑，会喊叫，以为房间里有人。
She was very sweet but then became very confused and would like call out and thought people were in the room.
她最后阶段出现了很多幻觉。
She was having a lot of hallucinations at the end.
看着这一切真的非常痛苦。
It was just really painful to watch.
是的。
Yeah.
我妈妈现在已被正式诊断为阿尔茨海默病。
My mom now has been formally diagnosed with Alzheimer's.
她八十多岁了。
She's in her eighties.
她住在一个专门照顾记忆障碍患者的机构。
She's in a facility specifically for memory care.
看着她逐渐衰退，这是我经历过最痛苦的事情之一。
And it's really one of the most painful things I've ever had to do is watch her deteriorate.
抱歉，其实不是这样。
And, sorry, it's not.
情况时好时坏。
It comes and goes.
所以我们有状态好的日子，也有觉得她好像在好转的日子。
So we have our good days, and we have our days where I think, oh, she's doing better.
但接着她会说出一些惊人的话，比如提到我爸爸还在房间里。
And then she'll say something so outrageous, you know, or talk about my dad being in the room.
他七年前就去世了。
He passed away seven years ago.
我刚刚意识到，我不想要这样。
I just realized, I don't want this.
所以我一直觉得这对我来说是不可避免的，但其实不是。
And so I just kind of grew up thinking this is inevitable for me, but it's not.
不是。
No.
是你教会了我这一点。
And you are the one teaching me that.
你是第一个告诉我，这并不是我的宿命的人。
So you're the first person to even say that this is not your inevitability.
我们是可以做些事情的。
There are things that we can do.
你还年轻，可以做到，
You're young enough to,
是的，完全对。
like Absolutely.
提前应对这件事。
Get ahead of this.
当然。
Of course.
跟我讲讲你的家人吧。
Tell me about your family.
我的家人也深受阿尔茨海默病和痴呆症的负面影响，这对我来说也涉及我的祖母，她非常出色，极其聪明。
My family has also been negatively impacted by Alzheimer's and dementia, and that for me also involved my grandmother who I mean, she was exceptional, extremely intelligent.
你还记得她得病前的样子吗？
You remember her without dementia?
是的，当然记得。
Oh, yes.
我主要是和祖母一起长大的。
Oh, I I grew up with my grandmother mostly.
我的父母都是核物理学家。
My my parents are nuclear physicists.
他们俩都是核物理教授。
They're professor on nuclear physics, both of them.
他们不像那种刻板印象中的核物理学家。
And they're not like the stereotypical nuclear physicist.
他们更像奥本海默那种类型。
They're more the Oppenheimer type I
我不太清楚那是什么意思。
don't know what that would be.
他们工作非常忙，嗯。
They did work a lot Mhmm.
我小时候就是这样。
When I was growing up.
所以是你祖母负责照顾你。
So your grandmother took on the caretaking.
是的。
Yes.
实际上，我几乎一直和我祖母在一起。
Effectively, I was almost always with my grandmother.
我记得她就是我的祖母。
And I remember her just being my grandmother.
但在我即将大学毕业、开始攻读博士学位时，她开始表现出认知衰退的迹象。
And then at some point when I was about to graduate from university and start my PhD, she started showing signs of cognitive decline.
这让我很震惊，因为她一直非常聪明敏锐。
That was shocking because she was always as sharp as a tack.
但这导致了至少十年的进行性认知衰退，出现了阿尔茨海默病和痴呆的症状，就像你提到的幻觉，这通常是混合型痴呆伴有路易体成分的标志，我祖母的情况也是如此。
But that led to at least a decade of dealing with progressive cognitive decline, Alzheimer's symptoms, dementia symptoms, like you mentioned, hallucinations, which is usually a sign of mixed dementia with some Lewy body components, which was the case for my grandmother as well.
她最后几年几乎一直卧床不起，显然过得并不快乐。
And she ended up spending at least years, her final years in bed, clearly not enjoying her life.
最令人心碎的是那种无助感。
And that was the most heartbreaking part, you know, the helplessness.
而对于我母亲——她是主要照护者——那时我已经在美国了，这对整个家庭来说都极其艰难，因为我们当时没有如今这样的帮助和支持。
And for my mother who was the primary caregiver, I was already in The United States at that point, that was brutal for the whole family because we do not have the kind of help and support that is available today.
更让我们全家震惊的是，我祖母一共有四个兄弟姐妹，三个姐妹和一个兄弟。
Even more shocking to us as a family was that So my grandmother was one of four siblings, three sisters and one brother.
她是最大的。
She was the oldest.
所以她是第一个患上阿尔茨海默病的。
So she was the first one to develop Alzheimer's.
几年后，中间的姐姐也开始出现类似的恶化，记忆力进行性衰退，最终发展为痴呆。
And then a few years later, the middle sister also started showing the same kind of deterioration and more progressive memory loss and then ended up with dementia.
而最小的妹妹也遭遇了完全相同的命运，但兄弟却没有，尽管他们都活到了相同的年龄。
And then the third one, the youngest sister also had exactly the same fate, whereas the brother did not, even though they all lived to the same age.
这令人担忧，因为一个人患病你或许会觉得是偶然，但当三个女性都表现出相同的遗传易感性时，这确实让人深受震撼。
So that was alarming because one person alone, you may be like, but when three, all women, express the same genetic vulnerability, that does hit you hard.
因此，我和妈妈一直密切关注相关研究进展。
And so my mom and I have been just so up to speed with the research.
我当然在做研究，但我的妈妈也非常积极参与，我爸爸也是。
I obviously do research, but my mom is also really, really participatory and so is my father.
我们在生活方式上做了很多小的改变。
And we have changed a lot of little things in terms of lifestyle.
我们了解目前医学界关于预防的所有知识。
We know everything about prevention, whatever we know at this point in the field about prevention.
我们确实做到了。
We do.
我们会深入研究这一点。
We will dig into that.
所以，是的，这让我深入探索，首先去了解遗传学。
So, yes, that sent me down the rabbit hole of trying to understand, first, genetics.
对吧？
Right?
阿尔茨海默病的病因是什么？
What causes Alzheimer's?
这是指什么？
Is this what?
当时已知的基因是哪个？
The gene known or at the time?
所以当时，也就是二十五年前，那时已经很清楚，有一些基因突变会导致阿尔茨海默病。
So at the time, which is now twenty five years ago, it was a long time, we did understand that there are genetic mutations that cause Alzheimer's disease.
至少有三个已知基因会发生突变，分别是APP基因（淀粉样前体蛋白）、早老素1基因和早老素2基因。
So there are mutations in at least three known genes, which are the APP, the amyloid precursor protein, and the presenilin one and two genes.
如果你携带了这三种基因中的任意一种常染色体显性遗传突变，就会直接导致阿尔茨海默病。
If you have an autosomal dominant genetic mutation, one of these three genes, that directly causes Alzheimer's disease.
这种情况会在家族中遗传，具有高度外显率且为常染色体显性遗传，这意味着如果你继承了这种突变，首先，你有百分之五十的概率会遗传到该突变。
And what happens is that it runs in families genetic transmission, but it's highly penetrant and autosomal dominant, which means that if you do inherit the mutation, number one, you have a fiftyfifty chance of getting the mutation.
如果你确实继承了它，外显率几乎接近百分之百。
If you do inherit it, penetrance is almost complete.
而对于
And for
我们的听众来说，外显率指的是你表现出该疾病的可能性。
our listeners, penetrance means the chance that you will express the disease.
这种突变非常强烈。
This mutation So, it's so strong.
这个
This
几乎总是会
is Almost always they're going to
如果他们活着，发病概率接近百分之百。
develop it if they It's live close to a hundred percent.
实际上，这从四十岁就开始了。
Well, that actually starts in the forties.
哇。
Wow.
所以，这种类型的阿尔茨海默病被称为早发性。
So, that's the type of Alzheimer's that is called early onset.
好的。
Okay.
我认为这很重要，因为很多人以为早发性阿尔茨海默病是六十岁左右，但实际上，当我们谈论早发性阿尔茨海默病时，指的是四五十岁。
I think this is important because a lot of people think that early onset is sixties, but early onset, when we talk about early onset Alzheimer's, it's forties and fifties.
哇。
Wow.
肯定是在65岁之前。
Certainly before age 65.
现在，好消息是，这些基因突变极其罕见。
Now, the sort of good news is that those genetic mutations are exceptionally rare.
好的。
Okay.
这些突变根据国家不同，平均存在于百分之二的阿尔茨海默病患者中。
They are found, depending on the country, in, on average two percent of all Alzheimer's patients.
所以，如果看整个人群，比例其实更低，对吧？
So, if you look at the entire population, it's actually even less, right?
但如果你看所有阿尔茨海默病患者，携带这种直接导致阿尔茨海默病的基因突变的人不超过百分之二。
But if you look at all patients with Alzheimer's, no more than two percent carry this kind of genetic mutations that cause Alzheimer's directly.
对于其他人来说——所以，
For everybody else- So,
百分之九十八的人没有遗传突变。
the ninety eight percent of people don't have a genetic mutation.
没有遗传突变。
Do not have a genetic mutation.
那究竟是什么？
So, what is it?
对。
Right.
在这种情况下，我们谈论的是风险。
So, in that case, we talk about risk.
而且我们现在确实了解阿尔茨海默病的分类了。
And we do understand that Alzheimer's is now classified.
首先，我们区分早发性与晚发性。
So, first of all, we look at early onset versus late onset.
早发性是指60岁之前，晚发性是指60岁之后。
Early onset before, I'm gonna say 60, late onset after age 60.
在晚发性阿尔茨海默病的范畴内，有些人接近60岁时就会出现阿尔茨海默病的症状。
Now, in the late onset Alzheimer's umbrella, some people do develop the symptoms of Alzheimer's when they're closer to 60.
很多人把这种情况称为早发性，从任何标准来看这都算早，但准确的说法是‘较早’，因为绝对意义上的早发性是指更年轻的时候，
And a lot of individuals refer to that as early onset, it's early by any standards, but the right term is earlier because early in absolute terms,
更少
Less
四十多岁而不是六十多岁。
forty's than and sixty's.
较早，是的，就是60岁。
Earlier, yes, it's 60.
这太可怕了。
It's horrible.
但好消息是，它并不是由基因引起的。
But the good news is that it's not genetically induced.
好的。
Okay.
然后，大多数人平均在72岁左右出现痴呆症状，这属于晚发性。
And then most people develop dementia around the age of 72 on average, and that is late onset.
我们有散发性阿尔茨海默病和家族性阿尔茨海默病两种情况。
Then we have sporadic Alzheimer's cases and familial Alzheimer's cases.
比如我祖母的情况，我们说家族聚集性，因为不仅是我祖母，她的姐妹们也有。
So like in my grandmother's case, we talk about familiarity because it's not just my grandmother, but also her sisters.
所以这是家族性晚发性。
So that is familial late onset.
这不是基因突变，但确实在家族中遗传。
It's not a genetic mutation, but it does run-in the family.
对你来说也是一样。
Same for you.
散发性意味着只有一人患病。
Sporadic means they're just one person.
家族中没有其他阿尔茨海默病病例。
No other cases of Alzheimer's in the family.
对子女和孙辈而言，风险显然不同。
And the risk is obviously different to the children and grandchildren.
这就是我们在讨论阿尔茨海默病时，用来区分不同类型所谈论的内容。
So this is what we talk about when we discuss Alzheimer's disease in terms of characterizing which type of Alzheimer's one has.
那你的博士呢？
So your PhD?
是的。
Yeah.
专业是什么？
Is in what?
我有
I have
一个神经科学和核医学的双博士学位，核医学是放射学的一个分支。
a dual PhD in neuroscience and nuclear medicine, which is a branch of radiology.
所以我经常做脑部成像。
So I do a lot of brain imaging.
因此，四分之三的女性，也就是75%，在这一混乱和过渡期间会出现脑部症状。
So three quarters of women, seventy five percent, gonna have brain symptoms during this chaos, during this transition.
是的。
Yeah.
脑雾、记忆力减退、焦虑和抑郁。
Brain fog, memory lapses, anxiety, depression.
所以我们谈到了心理健康和半衰期。
So we've got the mental health And the half life.
什么是脑雾？
What is brain fog?
让我们来澄清一下。
So, let's like clear it up.
也就是说，什么是脑雾？
Like, what is brain fog?
那么，人们什么时候应该担心呢？
Like, when should someone be worried?
是的。
Yeah.
这正是脑科学家开始将更年期视为阿尔茨海默病风险因素的原因之一。
It's one of the reasons that actually brain scientists started to look into menopause as a risk factor for Alzheimer's disease.
直到今天，来到我们在威尔康奈尔医学学院、纽约长老会医院阿尔茨海默病预防诊所的绝大多数患者，都是因为中年时期出现严重的脑雾，这种症状足以引发他们对早发性痴呆的担忧，而我一直在管理这个诊所。
And still today, the vast majority of patients who come to us at the Alzheimer's Prevention Clinic at Weill Cornell Medicine, New York Presbyterian, which I've run, come to us because of brain fog in midlife that can be so severe to really trigger concerns about early onset dementia.
因此，明确脑雾和阿尔茨海默病的区别，以及它们之间如何相互关联，是非常重要的，因为这种担忧确实是完全合理的。
So, it's really important to clarify what is brain fog and what is Alzheimer's and how one thing could lead to concerns about the others because it's really legitimate to be scared.
所谓脑雾，是一个非正式术语，人们用它来描述神经科医生所说的认知疲劳或精神疲劳，即在进行认知活动时感到异常吃力。
So, brain fog, it's a genetic term, it's a colloquial term that people use to describe what we in neurology refer to as cognitive fatigue or mental fatigue, which is this having a really hard time doing things cognitively.
对，没错。
You you Yes.
抱怨。
Complain.
尤其是那些在工作中认知能力很强的人。
Like Especially the ones who were, like, cognitive, high functioning at work.
是的。
Yeah.
教师、律师，你知道的，他们中的一些人辞去了工作，因为他们觉得自己无法完成过去轻而易举就能完成的任务。
Teachers, attorneys, you know, they're quitting their jobs, some of them, because they don't feel like they can complete the tasks that they used to it was mindless for them.
还有会计师，你知道的，那些经常处理数字的人
And accountants, you know, people who use numbers
是的。
Yeah.
真的很难受。
Are really struggling.
是的。
Yeah.
正是如此。
It's exactly that.
这是一种在认知努力面前出现的认知疲劳。
It's it's cognitive fatigue in front of a cognitive effort.
那些过去轻松自如、毫不费力的事情，现在却需要巨大的精力才能完成。
It's like things that used to be easy and just seamless now require a huge amount of effort.
我认为我们的一位患者形容这种感觉是，无论你做什么，你的大脑就是无法启动。
And it's I think one of our patients described it as this feeling that no matter what you do, your brain just won't turn on.
有一种感觉，仿佛不再是原来的自己，甚至有点像被毒害了，这样说你能理解吗？
There's this feeling of not being yourself, but also of almost being poisoned, if it makes sense.
就像如果任何人得过细菌感染一样，我曾经得过一次，那时我完全找不到自己的精力，尤其是脑力。
Like if anyone has ever had a bacterial infection, right, I had it once and I could not find my energy, my mental energy.
我觉得这和更年期有点像，虽然我本人没有经历过更年期，但我曾经历过产后脑雾。
And I think that's I'm not a menopausal close to it, I have not experienced that, but I had one experience of brain fog, postpartum.
在低雌激素状态下，是的。
In a low estrogenic state, yeah.
对。
Yes.
而且因为母乳喂养之类的，我完全想不起来孩子在哪里。
And with breastfeeding and whatnot that I just could not remember where my child was.
我完全惊慌失措了。
I was in complete panic.
我首先在打开冰箱前敲了冰箱门，那时候我就想，天哪。
I just, first of all, I knocked on the door of the fridge before opening the fridge, and that was already like, oh my god.
然后我发现我自己推着一个空婴儿车在外面走。
And then I found myself outside with the stroller empty going somewhere.
不可能。
No way.
不行。
No.
因为孩子和保姆在一起。
Because the baby was with the nanny.
但我完全不知道他们在做什么，那是我一生中唯一一次无法依赖自己的大脑，那真的吓坏我了。
But I had no idea what they was doing and that was the only time in my life I could not count on my brain and that was absolutely petrifying.
令人恐惧的。
Petrifying.
如果更年期就像那样，天哪。
So, if menopause is anything like that, oh my gosh.
他们完全能理解，因此我们正在努力帮助前来寻求帮助的女性，同时也通过开展研究
And they completely sympathize and that's why we're really trying to help women who come to us and also by doing the research
显然。
obviously.
因此，我们和其他人发现，目前脑雾与大脑能量水平的变化有关。
So what we and others have found is that there is an association at this point with brain fog and alterations in brain energy levels.
其他人还使用功能性磁共振成像（fMRI）证明，有脑雾的女性与没有脑雾的女性相比，大脑的功能连接发生了改变。
And other people have used fMRI, functional MRI, to show that the functional connectivity of the brain is altered in women with brain fog relative to those without
是的。
it.
我们
We
我们研究了可能涉及的分子机制。
have looked at the molecular mechanisms that may be involved.
我们发现这有点技术性，但磷酸肌酸和肌酸的比例升高了，你喜欢肌酸吗？是的，我喜欢肌酸。
And what we have shown is that it's a bit technical, but the ratio of phosphocreatine, creatine, you like Creatine, yeah, I like creatine.
ATP的生成量减少，意味着磷酸肌酸和肌酸的含量高于ATP。
To ATP is increased, meaning there is more creatine, phosphocreatine than ATP being made.
磷酸肌酸是大脑用来产生能量的缓冲物质，对吧？
So phosphocreatine is what the brain uses to make energy, is the buffer, right?
但你真正需要的是ATP。
But what you want is ATP.
你希望它们的比例保持在1:1。
So you want them to be in a one to one ratio.
而在一些与阿尔茨海默病受影响区域相同的脑区，ATP的生成受到了抑制。
Whereas the ATP production is suppressed in some of the same brain regions that are affected by Alzheimer's disease.
现在，我在网上看到过，虽然我没有数据支持，可能应该查一下相关研究，补充肌酸可能对脑雾有帮助。
Now, I've seen on the internet, well, I have no data to back this up, I probably should pull the studies, that creatine supplementation could be helpful with brain fog.
有什么数据能真正支持这一点吗？
Is there any data to really support that?
有一些
There are
主要是关于肌酸补充对认知影响的小规模研究和观察性研究。
small scale studies, observational mostly of creatine supplementation for cognition.
我认为我们还达不到那个程度。
I think we're not quite there.
有。
There.
是的。
Yeah.
根据我对肌酸生物学及其在磷酸肌酸形式下对大脑健康重要性的了解，我认为这非常值得研究，部分原因是女性体内的肌酸储备低于男性。
Given everything I know about the biology of creatine and how important it is for brain health in the form of phosphocreatine, I think that that is really something that's worth studying in part because the reservoir of creatine are lower in women than in men.
如果肌肉和身体中的肌酸水平较低，那么大脑中的肌酸水平从一开始也可能较低。
And if they are lower in muscle and body, there's also a chance that they're lower in brain to start with.
对。
Right.
而且这些更大的
And these bigger
腿部肌肉，更有可能拥有更高的脑容量。
leg muscles, the more likely to have higher brain volume.
我理解得对吗？
Did I read that correctly?
是的。
Yeah.
那就是说，你知道的，脚越小，皱纹越多，我们就会发现一些有趣的肠道关联。
That's that's you know, also the the smaller your feet and the higher your wrinkle all the time, we find gut relations that are interesting.
我不知道。
I don't know.
我不知道。
I don't know.
但我很希望看到这些研究开始进行。
But I would love to see those start.
是的。
Yeah.
我也希望如此。
I would like that.
我认为他们正在做一些观察性研究。
I think they're doing some observational stuff.
肌酸数据主要来自肌肉，对吧？还有健美运动员。
The creatine data mostly comes from muscle, right, and and the bodybuilders.
但我认为来自北卡罗来纳的艾比·史密斯、莱恩这些人已经开始关注，并在进行出色的认知研究，做一些测量工作。
But but I think Abby Smith Ryan and those people out of North Carolina are starting to look and and doing the great cognitive work, you know, doing some measurement there.
所以
So
我认为这非常值得深入研究。
I think it's something really worth looking into.
在研究尚未完成之前，就有太多东西变得有点流行了。
There are so many things that become a little bit trendy before the research has been done.
是的。
Yeah.
但这并不意味着它没有帮助。
But that doesn't mean It's not helpful.
并不意味着它可能没用。
Doesn't mean It could be.
好吧，你只是还不知道而已。
Well, you just don't know yet.
本集《Unpaused》由Alloy Health赞助播出。
This episode of Unpaused is brought to you by Alloy Health.
我们经常谈论荷尔蒙对情绪和能量的影响，但它们也对皮肤起着重要作用。
We talk a lot about hormones affecting mood and energy, but they also play a major role in your skin.
胶原蛋白、水分、弹性。
Collagen, hydration, elasticity.
在中年时期，当荷尔蒙水平开始变化时，你的皮肤也会随之改变。
And in midlife, when hormone levels start to shift, your skin changes too.
我第一次听说Alloy是通过一位身为皮肤科医生的密友。
I first heard about Alloy through a close friend who is a dermatologist.
她分享了真正能应对荷尔蒙性皮肤变化的产品有多么稀少。
She shared how few products truly address hormonal skin changes.
一旦我了解到Alloy的方法基于荷尔蒙科学和生理学，我就决定亲自试用。
Once I understood that Alloys approach is rooted in hormone science and physiology, I decided to try it myself.
它改变了我对这个人生阶段护肤方式的看法。
It changed the way I think about how skincare is at this stage of life.
Alloy的M4系列包括M4面霜、M4面部精华和M4眼霜。
Alloys M4 line includes the M4 face cream, M4 face serum, and M4 eye cream.
这些是含有雌三醇的处方级配方，雌三醇是你身体自然停止产生的黄金标准荷尔蒙，并且得到了临床研究的支持。
These are prescription strength formulas made with estriol, the gold standard hormone your body stops producing naturally, and they are backed by clinical research.
女性们正在寻求更光滑的肌肤、更好的紧致度以及更明亮、更均匀的肤色。
Women are seeking smoother looking skin, improved firmness, and a brighter, more even tone.
如果你的皮肤在变化，你的护肤方式也该随之改变。
If your skin is changing, your skin care should change too.
通过Alloy，你可以咨询医生，获得专业指导，并且治疗产品会直接送到你家门口。
With alloy, you consult with a doctor and receive expert guidance and have your treatment delivered right to your door.
前往myalloy.com并使用代码MCH20。
Head to myalloy.com and use code MCH20.
输入MCH20，即可享受首单20美元优惠。
That's MCH20 to get $20 off your first order.
围绝经期不是早期绝经。
Perimenopause is not early menopause.
它是一个独立的生理阶段。
It is its own distinct biological phase.
而这一阶段长期以来被忽视。
And it has been largely ignored.
我的新书《新围绝经期》讲述了月经停止前的七到十年。
My new book, The New Perimenopause is about the seven to ten years before your period stop.
这一转变绝非温和平静。
A transition that is anything but gentle.
荷尔蒙剧烈波动，对许多女性而言，正是在此时，焦虑、脑雾、睡眠紊乱、体重变化、情绪波动、关节疼痛以及‘我不再是原来的自己’这种不安感开始出现。
Hormones fluctuate wildly, and for many women, this is when the anxiety, brain fog, sleep disruption, weight changes, mood shifts, joint pain, and that unsettling feeling of I don't feel like myself anymore begin.
早在任何人提到‘更年期’这个词之前。
Long before anyone says the word menopause.
围绝经期往往悄然开始。
Perimenopause often starts quietly.
它首先在大脑中显现，然后波及身体，再蔓延至全身。
It shows up in the brain first, then the body, then everywhere else.
但太多女性被告知一切正常，没什么问题。
And too often, women are told nothing is wrong.
我写下《新围绝经期》，是因为在情况恶化之前，你值得拥有答案。
I wrote the new perimenopause because you deserve answers before things spiral.
你在耗竭之前值得被关怀，你值得拥有一份清晰的指南，来应对这个被医学长期忽视的转变。
You deserve care before burnout, and you deserve a clear roadmap for a transition that medicine has ignored for far too long.
《新围绝经期》现已在所有售书渠道开放预购。
The new perimenopause is now available for preorder everywhere books are sold.
了解更多并预购您的副本，请访问thepauselife.com。
Learn more and preorder your copy at thepauselife.com.
让我们谈谈它的情感层面。
Let's talk about the emotional side of it.
所以，你知道，我的很多患者偶尔会情绪爆发，他们前来就诊时完全焦虑不安，因为感到愤怒、恐惧、偏执、严重焦虑和易怒。
So, you know, the occasional outburst in a lot of my patients, they come in and they're completely worried because of rage and fear and paranoia and severe anxiety and anger.
而且，你
And, you
这影响着人际关系。
know, it's affecting relationships.
同时，对我们许多人来说，这也是人生中一段艰难的时期，要照顾年迈的父母和青春期的孩子。
And at the same time, it is a hard time of our lives for a lot of us with aging parents and teenagers.
你知道，我们正处在这种夹心层中。
You know, we're kind of in this sandwich area.
完美风暴。
Perfect storm.
那么，到底发生了什么？
So what's happening?
导致这些情绪变化的，是同样的生物力学过程吗？
Is it the same biomechanical process that's happening that's leading to this emotional changes?
是的。
Yeah.
所以，这至少在一定程度上反映了更年期在大脑中的结构特征。
So this is really in part at least reflective of the architecture of menopause in the brain.
雌激素受体遍布全身，但在大脑的某些特定区域更为集中，尤其是在最原始的脑区。
So estrogen receptors are a little bit everywhere, but they're more prevalent, they're more abundant in very specific brain regions and especially in the most primitive parts of the brain.
我们主要从动物研究中了解到这一点，但如今通过我们刚刚查看的脑部扫描图像，也在人类身上得到了证实，这让他们感到非常有趣。
And these we know mostly from animal studies, but we also now see with the brain scans that we just looked at, which is the first time in humans and they thought it was really fascinating.
它们在大脑的记忆中心表达最强烈，比如海马体和内侧颞叶，同时也大量存在于情绪调控中心，特别是位于海马体上方、与大脑其他部分相连的杏仁核，它调节着包括恐惧和共情在内的各种情绪。
They are most expressed in the memory centers of the brain, like the hippocampus and the medial temporal lobes, but also in the emotion control centers of the brain, like especially one region that's called the amygdala that sits right on top of the hippocampus and is connected to the rest of the brain, of course, and kind of regulates emotions, including fear, but also empathy.
所以这非常复杂。
So it's very complex.
然后，雌激素受体还存在于前额叶皮层，它负责思考、推理和抑制，非常重要；以及后扣带回皮层和楔前叶，这些区域更多涉及自传体记忆，即你去过的地方和做过的事情的记忆。
And then the estrogen receptors are present in the frontal cortex, which is in charge of thinking and reasoning and inhibition, very important, and the posterior cingulate cortex and precuneus, which are more about autobiographical memory, which is the memory of places you've been and things you've done.
是的。
Yes.
接着在脑干中，我们发现了所有与睡眠和清醒、睡眠周期相关的节点，同时也涉及压力。
And then in the brainstem where we find all the nodes for sleep and wake, the sleep cycle, but also stress.
当然，我们还有下丘脑和垂体腺，它们主要是生殖区域，但下丘脑和这两个腺体在自主神经功能中也起着重要作用，比如控制血压和心率。
And then of course we have the hypothalamus and the pituitary gland, is predominantly reproductive regions, but the hypothalamus also really both regions, actually both glands play an important role in autonomic function, which is like control of blood pressure, heart rate.
因此，所有最原始的功能实际上都受到雌激素及其与受体相互作用方式的影响，这意味着如果雌激素开始波动且四处乱窜，海马体就无法被正确激活。
So all the most primitive functionalities are effectively influenced by the presence of estrogen and the way it works with the receptors, which means if estrogen starts fluctuating and is all over the place, then the hippocampus is not activated correctly.
于是你无法巩固记忆，会感觉自己得了注意力缺陷多动障碍（ADHD）。
And then you don't consolidate memories and you feel like you have ADHD.
对。
Yes.
我们看到了。
We see.
一直如此。
All the time.
患者们不断抱怨这一点。
Patients complain constantly of that.
是的。
Yes.
他们意识到自己记不住事情，也很难集中注意力。
They become aware that they can't memorize things and they have a hard time paying attention to things.
这是注意力缺陷多动障碍，还是更年期，或者两者都有？
Is it ADHD or is it menopause or both?
或者
Or
两者都有。
both.
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那我们是不是在揭开某种此前就已存在的状况的面纱，
Do we unmask something that
我们之前就在应对的状况？
we're managing before?
一种身心层面的脆弱性。
Vulnerability.
也就是揭开面纱。
Unmask.
没错。
Yes.
杏仁核布满了雌激素受体。
Amygdala, full of estrogen receptors.
对。
Yeah.
如果雌激素开始波动或者分泌不足，杏仁核在调节情绪方面就会出现紊乱。
And if estrogen starts fluctuating or is not there, the amygdala will glitch in regulating emotions.
嗯。
Mhmm.
对吧？
Right?
所以你可能会在没有理由的情况下感到焦虑和恐惧。
So you may feel anxiety and fear when there's no reason for it.
你可能觉得这不仅仅是杏仁核的问题，而是整个网络的问题。
You may it's not just the amygdala, it's the whole network.
对吧？
Right?
但为了说明解剖结构，你可能会突然发怒，对吧？
But but just to explain the anatomy, you may get a rage, right?
如果你因为雌激素没有激活而没有睡觉，你的睡眠周期和褪黑素会完全紊乱，这会让情况更糟。
And if you haven't slept because the estrogen hasn't been activated, your sleep cycle and your melatonin is completely out of whack, that will make it worse.
如果你的前额叶皮层受到影响，你就更难抑制这种强烈反应，这种不属于你的反应。
And if your frontal cortex is impacted, you're going to have a harder time inhibiting this response, this strong response that is not you.
你的大脑是否正在过渡到基本在缺乏雌激素的情况下工作？
Is your brain transitioning to work mostly without estrogen?
因此，之前由雌激素支持的相同脑区，现在正处在重塑状态。
So, the same brain regions that were supported by the presence of estrogen before are now finding themselves in a state of remodeling.
是的，翻新。
Yeah, renovation.
对。
Yes.
所以，罗比实际上说，更年期是大脑的一次翻新工程。
So, Robbie actually says that, that menopause is a renovation project on the brain.
我想给你看一张幻灯片，如果我能找到的话。
I want to show you one slide if I find it.
所以我们现在看到的是绝经前女性与年龄匹配的男性之间的差异，女性大脑内部的所有纤维束都显示出更强的连接性标志。
So here we are looking at differences between premenopausal women and age controlled men when the women in all those fiber tracts inside the brain show more positive markers of connectivity.
因此，扩散性更强，也就是说，相对于同龄男性，这些特定脑区的连接性更好。
So there's more diffusivity, there's more it's just the brain is basically better connected in those specific parts of the brain relative to men at the same age.
所以我们有
So, we have
在某个阶段之前，女性的大脑功能优于男性。
better brain function than men up to a certain point.
连接性。
Connectivity.
而在围绝经期，情况就不同了。
And then this is what happens at the perimenopausal stage.
基本上没有差异了。
Are basically no differences.
这个情况，你会喜欢的。
This, and you're gonna love this.
哇哦。
Woah.
是的。
Yes.
哦，我喜欢这个。
Oh, I love that.
哇哦。
Woah.
这是绝经后女性的情况，而且比之前更好。
This is postmenopausal women and it's better than before.
哇。
Wow.
是的。
Yes.
所以，它会重新塑造。
So, it remodels.
它会重新塑造。
It remodels.
为了让我们它会重新塑造。
To make us It remodels.
连接
Connect
与以前不同。
Differently from before.
所以，大脑的这些部分——这是一项横断面研究。
So, these parts of the brain are, this is a cross sectional study.
我们现在正在随着时间的推移进行相同的纵向分析。
We're now doing the same analysis longitudinally over time.
要映射这一转变需要很长时间，因为这需要很多年。
It takes a long time to map the transition because it takes many, many years.
七到十年，而且
Seven to ten years and
然后你就进入绝经后了。
then you gotta go postmenopausal.
没错。
Exactly.
你谈的是一个十五年的
You're talking at a fifteen year
这需要一点时间。
It's gonna take a minute.
但我们现在已经有六年的数据了，所以我们在做这个分析。
But we do have six year data now, so we're doing that.
但这表明这是一项横断面研究。
But this suggests that this is a cross sectional study.
很多人一听到横断面研究就会皱眉头，但你必须从横断面开始，因为如果根本没有提示变化的差异，就不想浪费时间做纵向研究。
Lots of people kind of like give me like a wrinkled nose when something is done cross sectionally, but you have to start cross sectionally because you don't want to waste your time longitudinally if there's no differences that are suggestive of a change.
这表明一开始就有差异——围绝经期时没有差异，而绝经后阶段差异更明显。
These suggests that there are differences to start with, no differences when we're perimenopausal and more differences at the postmenopausal stage.
这里没有人接受激素治疗。
Nobody here is taking hormone therapy.
因此，这表明我们发现的是一种U形变化，其他研究方法也发现了类似模式。
So, that does suggest a U shape change that we find with other modalities as well.
女性的大脑衰老不是线性的。
Brain aging is not linear in women.
这很难建模和研究，但我们正在做。
And that is something that is difficult to model and study, but we are doing it.
我们正在进行深度表型分析和增加采样频率，现在正努力非常细致地绘制这一过程。
We're doing deep phenotyping and increased sampling, and we're trying to map it really, really carefully now.
但我认为这太出色了。
But I thought this was brilliant.
太惊人了。
It's amazing.
太惊人了。
It's amazing.
女性在年老时一直是智慧的守护者。
Women have been the wisdom keepers in their older age.
绝经后的女性，也就是祖母们，是智慧的守护者，传统上，如果她们活得足够久，就会传承她们的传统。
The postmenopausal women, the grandmothers were the wisdom keepers and that, you know, traditionally, if they lived long enough, you know, carried their traditions.
她们教导年轻一代。
They taught the younger.
这种演变方式真的很美好。
You It's kind of beautiful how that played out.
我觉得这很美好。
I think it's beautiful.
我认为我们这个领域所思考的是，这种重塑是必不可少的。
And I think what we're thinking as a field is that this remodeling is essential.
这非常重要，因为大脑和卵巢之间的联系是人体内一条非常重要的通路，维持它需要付出巨大代价。
It's very important because the link between the brain and the ovaries is a very big pathway in the body and is very expensive to maintain.
因此，一旦女性不再具有生育能力，继续维持所有这些与触发排卵和使身体具备孕育妊娠能力相关的连接和机制就毫无意义了。
So once women are no longer reproductive, it makes no sense to keep all these connections and all these mechanisms that are necessary to trigger ovulation and to potentially make your body able to host a pregnancy.
实际上，妊娠过程中的很多变化都源自大脑，对吧？
A lot of what happens in the pregnancy actually comes from the brain, Right?
一旦你不再具备怀孕的能力，大脑就非常有理由说：你知道吗？
And once you no longer have the ability to be pregnant, it's really cost effective for the brain to say, you know what?
我们来一次春季大扫除吧。
Let's do a little spring cleaning.
所有这些我不再需要的东西，最好都扔掉。
All this stuff I no longer need is best if I discard it.
这是我个人的理解。
That's my personal own interpretation.
但我认为这就是发生的事情。
But I think this is what happened.
这就是一个重新连接的改造过程，对吧？
And this is the renovation process where the connectivity is changed, right?
我们正在为一个非生育但依然富有成效的生命阶段做准备。
We're preparing for a non reproductive phase of life which needs to remain productive.
所以，大脑会重新调整自身。
So, the brain rearranges itself.
但与此同时，这样做其实很棘手，对吧？
But at the same time, that is tricky to do, right?
对。
Right.
这可能导致更年期的症状、紊乱，以及在一段时间内带来许多不适。
And that can lead to the symptoms of menopause, to the glitches, and unfortunately to a lot of discomfort for a certain amount of time.
但我们希望，这当然是有好理由的，对吧？
But it's for, we're hoping, of course, a good reason, right?
所以，当某种基因编程且预期会发生的事情发生时，这并不是一种病理。
So, when something that is genetically programmed and expected to happen happens, that is not a pathology.
是的。
Yeah.
这一点很重要。
And that's important to say.
更年期绝非轻松之事，对许多女性来说 certainly 不是件惬意的事，但它有其原因，她们的大脑和身体都具备应对它的能力。
Menopause is no walk in the park, it's certainly no picnic for so many women, but there's a reason for it and their brains and bodies are equipped to go through it.
好的。
Okay.
我们能做的就是在她们过渡期间提供支持，为大脑提供所需的工具和化学物质，帮助她们更平稳地度过更年期，降低患阿尔茨海默病、焦虑、抑郁、帕金森病等长期风险。
What we can do is to support them during the transition, is to provide their brains with the tools and chemicals that it needs to support us and go through a gentler menopause weight and lower long term risk of Alzheimer's and anxiety and depression and Parkinson's and whatnot.
所以对于正在经历脑雾或焦虑的听众，尤其是认知方面的症状。
So for someone who's listening who's having the brain fog or having the anxiety, you know, especially on the cognitive side.
但什么时候脑雾或认知症状应该引起警惕呢？
But when should the brain fog or the cognitive symptoms be a red flag?
什么时候你应该担心并决定去接受评估？
When should you worry and say, I need to go get evaluated?
我会建议无论如何都去检查一下，因为你需要一个基线数据。
Well, I would go regardless because you want to have a baseline.
至少在当今这个时代，我们确实拥有相应的工具、技术、可能性和通常的可及性。
For me, at least in this day and age, we do have the tools, have the technology, we have the possibility, we have the access often.
我认为在你相对年轻的时候，建立自己大脑和认知表现的基线是个好主意，因为当你年纪大一些时，你自己就是最好的参照标准。
I think it's a good idea to have a baseline of your own brain and your own cognitive performance when you're relatively young because you are the best reference for you when you are a little bit older.
通常来说，如果脑雾在更年期过渡期间出现，并没有理由过度担忧。
Now, there is no reason usually to get alarmed if brain fog tends to emerge during the transition to menopause.
如果你注意到月经变得不规律，同时伴有脑雾，这很可能是激素过渡期的一部分。当然，一旦进入更年期后，症状应该会好转，并在绝经后两到六年左右逐渐缓解——我知道这是一段很长的时间。
If you do notice that your period is changing and is getting more irregular and you also experience brain fog, that is most likely to be part of the hormonal transition once obviously you go to your And gets g better, should get better, it should resolve within two to six years of the final menstrual period, which I know it's a lot of time.
这段日子确实很长。
It's a long time.
很遗憾，这段时期确实很长，但症状终会好转。
It's unfortunately a lot of time, but it should get better.
但我们是可以提供支持的。
But we can We support can support it.
是的。
Yes.
在这一过渡过程中。
Through the transition.
没错。
Exactly.
在我们的诊所，我们会为这些情况提供激素治疗，患者通常反应很好。
In our clinic, we offer hormone therapy in these cases and they usually do very well.
而且还有更多研究正在进行，你知道的，会有更多选择。
And there's more research coming, you know, there are more options.
所以，知道有帮助可用，有治疗方法以及其他方式，包括生活方式的调整，这非常重要。
So, that is really important to know that help is available and there are therapies and other things, also lifestyle.
你是个大孩子了。
You're a big kid.
哦，是的。
Oh, Yeah.
我们来谈谈这个。
Let's get into that.
我们来谈一谈吧。
Let's into Let's do that.
如果脑雾变得更严重了，对吧？
If brain fog gets worse, right?
如果你记不起把钥匙放在哪儿了，那并不是阿尔茨海默病。
And if you don't remember where you put your keys, that is not Alzheimer's.
如果你不记得钥匙是干什么用的，那就是个问题。
If you can't remember what your keys are for, that is a problem.
我会再用这个。
I will use that again.
这太好了。
That is excellent.
但很多人来找我们做认知测试。
But then again, a lot of people come to us to get cognitive testing done.
我们做认知测试，你可以看到，比如有一个叫做MMSE的测试，我们总是用它来做筛查，得分范围是0到30分。
And we do cognitive testing and you can see that, for instance, there's this test that's called the MMSE that we always do as a screening, where the scores go from zero to 30.
像我这个年纪、你这个年纪的人，通常会得28到30分，对吧？
And most people my age, your age, will score 28 to 30, right?
如果你本来是30分，更年期让你降到28分，对你来说这简直是灾难。
If you are at 30 and menopause brings you down to 28, to you, that is a catastrophe.
但对我们来说，你仍然处于同龄、同教育水平女性的正常范围内。
To us, you are within normal range for women your age and educational level.
听到这个真是松了一口气。
And that is a huge relief to hear.
是的，我们理解您正在经历一种认知功能的变化，临床上称之为主观认知下降，因为您自己感受到了，意识到了，但通过标准化的认知测试却无法测量出来，这意味着您目前并没有痴呆。
That yes, we understand you are experiencing a change in cognitive performance that we refer to clinically as subjective cognitive decline because you feel it, you're aware of it, it's not measurable using standardized cognitive tests, which means you do not have dementia at this stage.
我喜欢这一点。
I love that.
如果您想不起来把钥匙放在哪儿了，
If you can't remember where you put your keys,
但如果您不知道
but if you don't know what
钥匙是干什么用的，您就需要去
the keys are for, you need to go
接受评估。
get evaluated.
这是个好情况。
That's a Okay.
好吧，让我们谈谈中年的大脑计划和应对策略，因为这里充满了希望。
All right, let's talk about our brain plan, our game plan for midlife because there's so much hope here.
是的。
Yes.
对。
Yes.
你知道，我们可以做的有很多。
You know, there's so much we can do.
比如玛丽·克莱尔的养老院预防项目是
Like Mary Claire's Nursing Home Prevention Program is
我通常这么称呼它。
what I like to call it.
预防骨质疏松症对我来说要容易得多，你知道，比起如何尽可能长时间地保持我的大脑功能。
Preventing, you know, preventing osteoporosis is much easier for me, you know, to deal with than how do I hang on to my brain function as long as I possibly can.
所以我真的不会感觉到有什么不同。
And so that I really, I won't know the difference.
你知道吧？
You know?
我会感到沮丧，但我真的不希望我的孩子们经历这些。
I'll be frustrated, but I don't want to do this to my kids.
你知道吧？
You know?
我不希望他们不得不做出这种令人心碎的决定，就像我的家人和我丈夫的家人正在经历的那样，如何最好地帮助我们的父母度过这一阶段。
I don't want them to have to go through this, like, gut wrenching decision making that my family and my husband's family is going through and how to best help our parents, you know, as they traverse this.
更年期是一种神经学上的转变，而不仅仅是生殖方面的。
So menopause is a neurological transition, not just a reproductive one.
是的。
Yes.
那么女性实际上能做些什么来保护大脑呢？
But what can women actually do to protect their brains?
让我们来谈谈影响大脑健康的关键生活方式因素。
So let's talk about the key lifestyle factors involved in brain health.
是的。
Yes.
那么我们先从睡眠说起。
So we're gonna start with sleep.
哦，是的。
Oh, yes.
抱歉。
Sorry.
是的。
Yes.
我觉得这可能是个问题，对我们大多数人来说可能是最重要的事情之一。
Think that's a problem Probably one with of a lot most important us, things.
我听说过
Isn't I've heard
睡眠被称为清理循环。
sleep is called as the wash cycle.
是的。
Yes.
那么，‘是的’是什么意思？
So what does Yes.
那
That
这意味着，大脑每分钟都在不停地监督身体的其他部分。
What that means is that the brain, minute after minute, is always busy supervising the rest of the body.
大脑一直在不断地思考、记忆、感受，甚至过度思考。
The brain is constantly either thinking, memorizing, feeling, is very Overthinking.
希望你记错了。
Wish you were misremembering.
但同时也监督着身体的其他部分。
But also supervising the rest of the body.
好的。
Okay.
甚至连心率、呼吸和运动，这些都需要时刻保持活跃。
Even heart rate and breathing and moving, all of that needs to be active at all times.
一天中，大脑唯一能真正照顾自己的时间就是睡眠，特别是慢波睡眠或深度睡眠，这时你的身体完全静止。
The only time in the day that the brain can actually take care of itself is during sleep and specifically during slow wave sleep or deep sleep, which is when your body is completely still.
你一动不动，只是非常安静地呼吸。
You are not moving, just breathing very quietly.
大脑可以放下所有其他事务，激活一种叫做类淋巴系统的机制，这就像一个汽车清洗系统。
The brain can let go of everything else and activate a system that is called the glymphatic system, which is like effectively like a car wash.
有液体开始在大脑中流动，清除毒素、废物和阿尔茨海默病的斑块。
There's like fluid that starts moving throughout the brain, removing toxins, removing waste, removing Alzheimer's plaques.
这时许多清除机制都会被激活。
That's when a lot of clearance mechanisms are activated.
氧化应激被消除，炎症被排出，而且
The oxidative stress is removed, the inflammation is flushed out, and
睡眠是全天累积而来的。
the sleep is kind of accumulated through the day.
所有那些，是的。
All the things that yeah.
嗯，它是一个器官。
Well, it's an organ.
有很多活动在进行。
There's a lot of activity going on.
所以，如果你的睡眠被打断，尤其是深度睡眠受到影响，失去了这个睡眠窗口，长期下来会有后果，因为所有的毒素都无法被清除，对吧？
So, you don't sleep, if your sleep is fragmented and you sleep, especially your deep sleep is impacted and you lose that window of sleep, that over time has consequences because then all the toxins will not be cleared out, right?
它们会在大脑中积累。
They will accumulate in the brain.
阿尔茨海默病的斑块会留在大脑中。
The Alzheimer's plaques will stay in the brain.
炎症也可能留在大脑中。
The inflammation may stay in the brain.
因此，睡眠卫生和睡眠保护是大脑健康和阿尔茨海默病的一种非常重要且新近发现的保护因素，而睡眠剥夺则是一个风险因素
So, sleep hygiene and sleep protection is a very important and just recently discovered protective factor for brain health and Alzheimer's disease, whereas sleep deprivation is a risk factor
因此，目前在心血管疾病中，睡眠已被认定为一个风险因素。
So for now sleep is now, in cardiovascular disease, now characterized as a risk factor.
我们需要多少睡眠？
How much sleep do we need?
你知道吗？
You know?
这是个非常好的问题。
That's a really good question.
那么，为什么会有半夜醒来的情况呢？我的很多患者都抱怨这一点，包括
And then why do these middle of the night wake ups, which a lot of my patients complain of, including
其中一个可能的机制与更年期有关。
So one potential mechanism is related to menopause.
当然，压力和焦虑是另一个问题。
And, of course, stress, anxiety, that is a different story.
但对于经历更年期的女性来说，睡眠紊乱可能存在激素方面的因素。
But for women who are going through menopause, there can be a hormonal component to sleep disruption.
而可能发生的情况是，所有这些不同的激素共同作用，使得内分泌系统处于波动状态。
And what can happen is that all these different hormones work together is the hormonal system that is in a flux.
我们总是谈论雌激素和孕激素，但其他激素也受到影响。
We're always talking about estrogen and progesterone, but other hormones also are impacted.
特别是压力激素和睡眠激素。
And in particular, stress hormones and sleep hormones.
皮质醇。
Cortisol.
皮质醇。
Cortisol.
还有褪黑素。
And melatonin.
好的。
Okay.
对于皮质醇而言，其关系已被充分阐明：身体需要一种共同的前体物质——孕烯醇酮，来合成性激素和皮质醇这种压力激素。
So, for cortisol, the relationship is well characterized in that the body needs a common precursor, which is pregnenolone, to make both sex hormones and cortisol, the stress hormone.
所以，如果你压力非常大，身体就会不得不将大部分或更多的孕烯醇酮用于制造皮质醇。
So, if you're super stressed out, the body is going to have to use most or more of the pregnenolone to make the cortisol.
这意味着它无法制造那么多的性激素。
And that means it cannot make as much of the sex hormones.
哇。
Wow.
是的。
Yes.
这就是为什么压力会耗尽你的激素。
That's why stress sinks your hormones.
而那些压力非常大的女性可能会经历更严重的更年期症状，因为性激素的原料供应减少了。
And women who are really, really stressed out may experience more severe symptoms of menopause because you have less availability.
出血周期会被消耗掉。
The bleeding loop gets eaten up.
是的。
Yes.
荷尔蒙开始沿着一条小通路转化为皮质醇。
Hormone started running little pathway to make cortisol.
是的。
Yes.
对于褪黑素来说，情况也类似：如果压力和皮质醇水平很高，就会抑制褪黑素的生成。
And for melatonin, it's a similar problem where if stress and cortisol, say cortisol is high in your body, that suppresses melatonin production.
通常，褪黑素会在深夜到凌晨一点到三点之间达到峰值，但之后会持续存在于体内，除非你压力极大，这时皮质醇会在凌晨两点左右开始升高。
So, what happens is that usually melatonin peaks around that time of night before day one to 3PM window, but then it remains in the system unless you're super stressed out, in which case cortisol kicks in around two in the morning.
哇。
Wow.
所以这是一个完整的机制。
And so it's a whole mechanism.
你知道，当性激素受到影响时，压力激素和睡眠激素也会一并被打乱。
You know, when the sex hormones are disrupted, the stress hormones are disrupted, the sleep hormones are disrupted.
所以，你可以从任何一个环节入手。
So, you can start at any of these nodes.
互联网上充斥着各种健康疗法，你知道的，但我没有任何数据。
The internet is full of all of these wellness cures, you know, and I have no data, you know?
对。
Right.
我们怎么降低皮质醇？
How do we lower cortisol?
我知道我们可以做压力管理、写日记，你知道的，但有没有补充剂？
I know we can do, you know, stress reduction, journaling, you know, but are there supplements?
有没有，你
Are there, you
知道，没有皮质醇。
know No cortisone.
是的。
Yeah.
据我所知，没有。
Not that I'm aware of.
好的。
Okay.
网上有很多说法，说吃这个就能降低你的……天啊。
A lot of claims out there to take this and we'll lower your Oh, god.
各种网络上的宣称。
All kind of internet claims.
你知道，买我的补充剂，我就能帮你降低。
You know, buy my supplement and I'll lower
我不了解有任何补充剂能直接降低皮质醇。
not aware of any supplements that can directly lower cortisol.
听起来不错。
Good to hear.
已被证实能降低皮质醇水平的，就像你说的，是冥想和减压。
What has been shown to lower cortisol levels is like you said, is meditation, stress reduction.
如果你能睡好觉，也应该有助于降低压力激素水平。
If you can sleep, that should also lead to a reduction in stress hormone levels.
因此，优先保证睡眠也非常重要。
So prioritizing sleep is also really important.
这更多是个人经验之谈，但甘氨酸镁可能有所帮助。
And this is more anecdotal than anything else, but magnesium glycinate may be helpful.
别问我有没有临床试验。
And do not ask me for clinical trials.
我们不可能为每件事都做临床试验。
We can't do clinical trials for everything.
但至少对几位女性来说，甘氨酸镁特别有助于放松肌肉，帮助入睡并保持睡眠，从而对皮质醇通路产生不同影响。
But at least for several women, magnesium glycinate in particular can help relax the musculature and help you fall asleep and stay asleep, which then has a differential effect on the cortisol pathway.
褪黑素可以帮助你入睡并保持睡眠，这也可能有助于降低胆固醇。
Melatonin can help you sleep and stay asleep, and that also may help lower cholesterol.
换句话说，所有有助于睡眠的事情，也可能对皮质醇产生降低作用，但这不是直接的。
So all the things that help you sleep, in other words, may also have a lowering effect on It's not direct.
我会说这是间接的，但通过中介机制实现的。
Would say it's more indirect, but mediated.
放松身体，然后
Relaxing the body and then
就是锻炼。
it just Exercise.
锻炼。
Exercise.
这正是我下一个问题。
That's my next question.
所以那些身体健康的女人
So women who are fit
在中年时期，无论‘健康’如何定义，患痴呆症的风险低百分之三十。
in midlife, whatever fit is defined as, have a thirty percent lower dementia risk.
这些是中年时期心血管健康水平最高的女性。
Those are the women who have the highest level of cardiovascular fitness in midlife.
是的。
Yes.
所以，运动对
So to What
大脑有什么作用？
is exercise doing to the brain?
运动通过多种途径支持大脑健康，我认为最有趣的是直接途径。
Exercise supports brain health through multiple pathways and the most interesting ones, I believe, are the direct pathways.
第一个途径是增加大脑的血流量。
So the first one is by increasing blood flow to the brain.
这非常重要，因为它支持供氧和营养输送。
That is very, very important because that supports oxygenation and nutrient transmission.
因此，你实际上是在为大脑提供养分。
So, you're effectively feeding your brain.
运动还具有抗炎作用，并减少氧化应激，而大脑对这些非常敏感。
Exercise is also anti inflammatory and reduces oxidative stress, which the brain is very sensitive to.
几年前，一项非常有趣的发现发表在《科学》杂志上：当肌肉在运动中收缩时，会产生一种名为‘鸢尾素’的肽，这个名字源自彩虹女神，非常优美。
And then there was a really super interesting discovery just a couple of years ago, it came out in Science, that when muscles contract as part of exercise, they produce a peptide that is called iridescent from goddess of the rainbow, which is very pretty.
而iridin可以穿过血脑屏障，对吧？
And iridin can cross the blood brain barrier, right?
一旦它穿过血脑屏障，就会像雌激素一样，促进BDNF的生成，并直接减少神经元中的促炎细胞因子。
And once it crosses the blood brain barrier, it supports like estrogen, it supports BDNF production and reduces the amount of pro inflammatory cytokines directly in neurons.
所以，这是运动直接支持大脑的一种美妙方式，太棒了。
So that's a beautiful way that exercise can directly support Amazing.
大脑，而且当谈到阿尔茨海默病时，这一点尤其重要。
Brain And look, this is when it comes to Alzheimer's disease.
我非常喜欢这张幻灯片。
I love this slide.
前几天我还在找这张图。
I was looking for this the other day.
好了，找到了。
Okay, here we go.
太好了。
Oh, good.
这是我们目前所了解的阿尔茨海默病的可调节风险因素，这些因素累计导致了超过百分之四十的阿尔茨海默病病例。
So this is what we currently know about the modifiable risk factors for Alzheimer's disease, which cumulatively account for over forty percent of all Alzheimer's cases.
好的。
Okay.
这些都与生活方式有关。
These are all lifestyle based.
我标出了每种因素所对应的风险比例。
And I specified what percentage of risk they each account for.
如果你看一下，运动不足——当然可以通过锻炼来弥补——在全球范围内导致了超过百分之二的阿尔茨海默病病例。
And if you look, exercise, actually, physical inactivity, which can be obviously offset by exercise, accounts for over two percent of all Alzheimer's cases globally.
然后我们还有过量饮酒，所谓过量是指每天超过两杯。
And then we have things like excessive alcohol consumption, which excessive means more than two glasses a day.
社交孤立。
Isolation.
我们还有中年期抑郁，这对女性的影响比对男性更大。
We have depression in midlife, more of an issue for women than for men.
我们还有空气污染。
We have air pollution.
他们说低教育实际上更像缺乏智力刺激。
Have low they say low education is more like low intellectual stimulation.
对。
Right.
与其只看受教育年限，尽管这也是一个因素，更应关注未经治疗的听力和视力损失。
Would say rather than just years of schooling, although that is a factor as well, hearing and vision loss if untreated.
因此，眼镜和助听器也正成为预防阿尔茨海默病的重要手段。
So glasses, hearing aids are becoming important for Alzheimer's prevention as well.
脑外伤，尤其是伴有意识丧失的情况，还有吸烟，以及心脏病风险因素。
Tumor brain injury, especially with loss of consciousness, smoking, and then the heart disease risk factors.
比如糖尿病、高血压和高LDL胆固醇。
So, diabetes, hypertension, and high LDL cholesterol.
这些共有14项，已被确认为可改变的阿尔茨海默病风险因素，对吧？
Those are 14 and have been formalized as risk factors for Alzheimer's disease that can be modified, right?
任何人都可以采取这些措施中的任何一项，以降低患阿尔茨海默病的风险。
Anyone can do any of all these things if necessary to reduce the risk of Alzheimer's.
现在我们也在关注其他因素，比如睡眠，这非常重要，还有饮食和营养，显然也很重要。
And now we're looking at other things like sleep, very important, diet and nutrition, obviously important.
那GLP呢？
What about GLP ones?
我们还达不到那一步。
We're not there yet.
不，不，不，不，不。
Everyone's No, no, no, no, no.
还没到那一步。
Not yet.
还没到那一步。
Not yet.
好的，那我们来谈谈食物吧，因为我在你的书中特别喜欢你花了大量篇幅讨论营养。
All right, well, let's talk about food because what I loved in your books is that you spend a lot of time talking about nutrition.
我热爱化学，而营养学本质上就是生物化学。
I love chemistry, and nutrition is effectively biochemistry.
我女儿在上医学院之前的专业是营养学，凯瑟琳现在是医学院三年级学生，她的本科专业就是营养科学。
My daughter's undergrad before med school, Katherine's a third year med student, and so her undergraduate is nutrition science.
她上的是一门生物化学课程，而不是为一千人做饭的那种课程。
She went to a biochemistry program, not the cooking for a thousand people program.
你知道，营养科学其实有两方面的发展方向。
You know, they're kind of the nutrition science goes two ways.
你知道吗？
You know?
是的。
Yeah.
对。
Yeah.
她非常喜欢，我认为这为她打下了非常坚实的基础，对于
And she absolutely loved it, and I think it's such a strong foundation for her, for
医学太棒了。
medical It's so good.
我也没有在学校学过营养学，但我是自学的。
I also I did not study nutrition at school, but I am kinda self taught.
有段时间，我想：给我找来所有化学书籍吧，因为我学到的关于大脑健康的所有知识——比如钠钾泵，还有血清素是由色氨酸合成的。
At some point, I was, okay, just get me every chemistry book because all the things I'm learning about brain health, all the sodium potassium pumps, you know, serotonin is made of tryptophan.
这些都来自食物中的营养素，对吧？
And these are all nutrients that come from food, right?
它们不是大脑自己产生的，而是从外部摄入的。
They're not made by the brain, they are imported.
所以我特别喜欢。
So I loved it.
我花了很多时间研究：我们应该吃些什么来滋养大脑？
I spent a lot of time So what studying should we the be eating for our brains?
大脑是一个有趣的器官。
The brain is an interesting organ.
如果你为了大脑健康而健康饮食，那么你也会对身体有益，但反过来却不一定成立。
And if you eat healthy for your brain, you're also eating healthy for the body, not necessarily the other way around.
所以大脑的要求更具体。
So the brain is more specific.
好的。
Okay.
相对于其他器官，大脑是个有点挑食的家伙，它主要需要抗氧化剂，比如维生素A、C、镁和维生素E，特定的氨基酸，尤其是必需氨基酸——这些来自多种食物，以及主要存在于鱼类、坚果和种子中的Omega-3脂肪酸。
It's a little bit more of a picky eater relative to other organs and it loves predominantly, and it needs predominantly antioxidants like vitamin A, C, magnesium and vitamin E, specific amino acids, especially the essential amino acids, which come from many different foods, and omega three fatty acids, which are predominantly from fish, nuts, and seeds
嗯。
Mhmm.
如果你愿意，也可以来自一些海洋藻类。
And some marine algae, if you wish.
鱼体内的Omega-3
That's where the fish
是它们吃了藻类获得的。
get the omega-three is they eat the algae.
所以这是食物链的一部分。
So it's part of the food chain.
所以如果你不能吃鱼或者对鱼过敏，可以服用补充剂。
So if you can't tolerate fish or you're allergic, you can get the Supplement.
藻类为基础的补充剂。
The algae based supplement.
是的。
Yeah.
当然。
Absolutely.
显然，葡萄糖也很
And obviously glucose is very
重要
important
但对于大脑来说，适量即可，你知道，不需要吃很多，但少量对大脑功能很重要。
But for brain within reason, you know, you don't need to eat a ton, but a little bit is important for brain function.
此外，它还参与谷氨酸的合成。
Also for the synthesis of glutamate.
因为很多人只把葡萄糖看作一种糖，对吧。
Since a lot of people just look at glucose as a sugar, Right.
但葡萄糖具有多种功能。
But glucose has a number of functionalities.
对于大脑来说，葡萄糖是谷氨酸的构建模块，而谷氨酸是大脑中最普遍的神经递质，也是合成主要抑制性神经递质GABA所必需的。
And for the brain, it's the building block of glutamate, which is the most prevalent neurotransmitter in the entire brain and is needed to synthesize GABA, which is the prevalent inhibitory neurotransmitter.
所以，葡萄糖不仅仅是能量来源——当我看到生酮饮食兴起时，我有点震惊，因为葡萄糖不仅对供能重要，还对合成我们体内最丰富的神经递质至关重要。
So, glucose is not just And I'm thinking when the keto diets came out, I was a little bit like, woah, because it's important not just for energy but also to synthesize the most abundant neurotransmitters that we have.
为什么超加工食品对大脑健康有害？
Why are ultra processed foods so bad for brain health?
它们是间接有害的。
They're bad indirectly.
这些食物和营养物质本不该穿过血脑屏障，但它们会增加身体其他部位的炎症，并且肯定会对肠道产生类似毒性的效应，进而导致全身和大脑出现广泛的负面影响。
So, those kinds of foods and nutrients should not be able to cross the blood brain barrier, but they do increase inflammation in the rest of the body and they do have almost like a sort of toxic effect in your gut for sure that then leads to widespread negative effects throughout the body and brain.
在超加工食品的生产和制造过程中使用了大量化学物质，而我们的身体根本无法应对这些物质，这会导致氧化应激和炎症，进而引发各种健康问题，对大脑健康也产生负面影响。
There are a lot of chemicals that are used in the synthesis and making of ultra processed foods that our bodies are just not equipped to handle, which then leads to oxidative stress and inflammation and those sort of medical issues really that then also negatively impact brain health.
对心脏有益的，对大脑也有益。
What's good for your heart is good for your brain.
对心脏有害的，对大脑也有害。
What's bad for your heart is bad for your brain.
超加工食品对我们的几乎所有器官都有害。
And ultra processed food is bad for pretty much every organ we have.
你认为有哪些补充剂是炒作过度的，还是
Are there any supplements you think are hype or are
对大脑健康真正有效的？
realistic for brain health?
是的。
Yeah.
我希望我们能有更多的数据。
I wish we had more data.
我认为有些营养素对大脑健康确实有益，如果你缺乏或亚临床缺乏某些营养素，补充可能有所帮助。
I think there are some nutrients for the supplements that are clearly beneficial for brain health and it makes sense that if you are deficient or subclinically deficient in some nutrients, then supplementation might help.
我在想B族维生素。
I'm thinking B vitamins.
我们知道，尤其是B12，对很多人来说都是个问题，因为随着年龄增长，从食物中吸收B12会变得更加困难。
So, we do know, especially B12 is an issue for a lot of people because as we get a little bit older, it becomes more difficult to absorb in from the foods that we eat.
几乎所有的老年人都缺乏B12，但他们自己却并不知道。
And almost all elderly individuals are B12 deficient and just don't know that.
因此，检测B12水平非常重要。
So, it's important to have that measured.
我们检查了我们所有患者的B12水平。
We checked B12 levels in all of our
是的，叶酸和B6对大脑健康也非常重要。
patients.
是的，叶酸、B6这些也是对大脑非常重要的维生素。
Yeah, the folate, B6, those are really important brain vitamins as well.
临床试验的结果参差不齐。
Clinical trials have shown mixed results.
我认为我们证据最充分的补充剂是欧米伽-3脂肪酸。
I think that the supplement that we have the best evidence for is omega-three fatty acids.
我完全偏向抗氧化剂。
And I'm 100% partial to antioxidants.
坦白说，我没有利益冲突。
Full disclosure, I have no conflicts of interest.
我什么都不卖。
I don't sell anything.
我喜欢抗氧化剂，因为我认为大脑特别容易受到氧化应激的影响，而氧化应激实际上是细胞和神经元衰老的主要原因。
I love antioxidants because I think that the brain is exceptionally prone to oxidative stress, is actually the major cause of cellular and neuronal aging.
大脑对氧化应激完全无能为力。
And the brain is completely powerless against oxidative stress.
对抗这种影响的唯一方法是通过饮食摄入维生素A、C、E、硒和抗氧化矿物质。
The only way to counteract the effects is by importing vitamin A, C, E, selenium, and the antioxidant minerals through the diet.
但很少有人摄入足够的水果、蔬菜、坚果和种子来确保充足的水平。
And very few people eat enough fruit and vegetables and some nuts and seeds to really ensure adequate levels.
然后这就因人而异了。
And then it depends.
我相信精准医学的方法。
And I do believe in a precision medicine approach.
我知道你也这么认为。
Know you do too.
并不是每个人都能获得像俄亥俄州坐在沙发上听的那位女士那样的资源，她只有一位全科医生，能告诉她的无非是些常规建议，我们能对她说什么？
Not everyone So has access to like for the lady on the couch in Ohio listening, you know, who just has a primary care doctor who's gonna do standard, you know, like, what can we tell her?
例如，如果你曾经吸烟——这是我一生中最大的遗憾之一。
Well, for instance, if you are a former smoker, which this is one of the biggest regrets of my life.
我也是。
Same.
我23岁就戒了。
I quit at 23.
我也是。
Same.
我也是。
Me too.
你知道吗，在意大利，我长大时，周围没人抽烟。
You know, in Italy, I was growing up there and everybody Nobody else smoked.
天哪。
Oh my god.
我也抽过。
And so did I.
我真的希望我没抽过。
And I really wish I hadn't.
但我确实抽了，我知道。
But I did, I'm aware.
我们知道吸烟会严重影响卵巢功能和大脑健康，你该如何对抗吸烟引起的活性氧的负面影响，以及可能由此导致的表观遗传修饰，进而引发更多氧化应激？抗氧化剂。
And we know that smoking is a major risk for ovarian function and for brain health, how do you counteract the negative effects of reactive oxygen species that are caused by smoking and the possible epigenetic modifications that then lead to more oxidative stress being produced, antioxidants.
所以，我理解人们希望看到补充剂的临床试验。
So, I understand that people want clinical trials of supplements.
我不确定在财务和投入方面这是否切实可行。
I'm not sure how feasible that is financially and in terms of commitment.
但我想说，如果你是前吸烟者，使用抗氧化补充剂没有任何坏处。
But I would say if you are a former smoker, there is no downside to using antioxidant supplements.
举个例子，什么是抗氧化剂？
For example, what would an antioxidant be?
为了我们的听众。
Just for our listeners.
维生素C。
Vitamin C.
维生素C。
Vitamin C.
是的，那就是
Yeah, That's
就是首推的那一个。
the number one.
而且就连那位博士，
And even Doctor.
鲍林，你知道的，就是发现维生素C还凭这个发现拿了诺贝尔奖的那个人，他自己就服用大剂量的维生素C。
Pauling, you know, who's the one who discovered vitamin C and then won the Nobel Prize for the discovery, he took very high doses of it.
我不是说大家要
I'm not saying anyone
得吃大剂量的，把自己的胃都折腾坏了
should take high doses and tear their stomach up
一直到他去世那天都是如此
Until the day he died.
而且他的身体状态好得不得了
And he was as healthy as anyone can be.
当然，这只是一个人的例子，他可是诺贝尔奖得主
Now, that's one person, Nobel Prize.
但这毕竟只是一个人。
That's still one person.
我会说，日常摄入适量的维生素C，尤其是液态的。
I would say regular amount of vitamin C, especially liquid.
液态维生素在吸收方面确实很好。
Liquid vitamins are really good in terms of being absorbed.
吸收。
Absorption.
这很有用。
Good to know.
好的。
Alright.
那么，摆在明面上的问题是，大家谈了很多，也很担忧。
So elephant in the room, lots of talk, worries.
更年期学会的会议专门设了一个部分讨论这个。
The menopause society meeting had a whole section on this.
我们来谈谈激素疗法与痴呆症。
Let's talk about hormone therapy and dementia.
是的。
Yes.
那么，我们了解些什么？
This What do we know?
我们了解什么，又有哪些还不知道？
What do we know and what we do not know yet?
我认为这两点都非常重要。
And I think both are really important.
这正是讨论语言重要性的绝佳时机，不知是否合适。
And this is the perfect situation to talk about the fact that language matters, if it's okay.
当然。
Absolutely.
双向都是如此。
In both directions.
是的。
Yes.
那么，我们知道了什么？
So, what do we know?
我们知道，我们还没有完成所有本可以做的工作。
We know that we have not done all the work that we could have.
这是一个事实。
That is a fact.
只有一项临床试验曾研究过激素疗法在预防痴呆方面的应用，那就是我们之前提到的女性健康倡议。
There is only one clinical trial that ever looked at hormone therapy for dementia prevention, which is the Women's Health Initiative that we mentioned before.
他们远远领先于时代。
They were way ahead of their time.
这是一项针对绝经多年女性的出色研究。
Fantastic study in women who were postmenopausal by decades.
女性健康倡议中有一部分被称为女性健康倡议记忆研究，其中专门测试了激素疗法，即高剂量口服结合马雌激素和醋酸甲羟孕酮作为孕激素，有或没有醋酸甲羟孕酮，以及安慰剂。
There's a part of the Women's Health Initiative that is called the Women's Health Initiative Memory Study, where they specifically tested hormone therapy, which in this case is high dose oral conjugated equine estrogen and MPA as the progestin with or without an MPA and placebo.
他们对这些女性进行了若干年的随访。
And they followed these women for a certain number of years.
他们发现了两件事。
And what they showed is two things.
第一，他们无法以阿尔茨海默病作为主要终点，因为发展为阿尔茨海默病的女性太少。
Number one, they could not use Alzheimer's disease as the endpoint because too few women developed Alzheimer's disease.
因此，他们不得不将终点改为痴呆。
So, they had to switch their endpoint to dementia.
不，痴呆并不等于阿尔茨海默病。
No, dementia is not Alzheimer's.
对。
Right.
阿尔茨海默病是唯一一种表现出女性与男性发病率差异的痴呆类型。
Alzheimer's is the only form of dementia that shows the female to male disparity.
据我们所知，女性在妇女健康倡议记忆研究中所患的其他类型痴呆主要是血管性痴呆，其激素相关性低于阿尔茨海默病，还有一些是混合性痴呆。
The other forms of dementia that the women in the Women's Health Initiative, memory study developed was predominantly vascular, where there is a lower hormonal component relative to Alzheimer's as far as we know, and some had mixed dementia.
所以，这是一个重要的发现。
So, that was an important finding.
然而，当他们观察女性患痴呆症的比率时，发现接受结合型马雌激素和醋酸甲羟孕酮治疗的女性群体中，痴呆症的发生率是安慰剂组的两倍。
Nonetheless, when they looked at the rates of how many women develop dementia, they found in the conjugated equine estrogen and NPA group, there was an increased rate, double the rate of dementia in women who were taking the hormones as compared to placebo.
病例的绝对差异很小，仅比安慰剂组多出约12名女性。
The absolute difference in cases was small, was about twelve more women than in the placebo group.
在仅接受雌激素治疗的女性群体中，风险增加了百分之五十，但这一结果并不显著。
In the group of women who were taking only the estrogens, there was a fifty percent increased risk that was not significant.
这些结果不适用于中年女性。
These results are not generalizable to midlife women.
对。
Right.
因为这些受试者年龄要大得多。
Because these patients were much older.
是的。
Yes.
这正是我们之前讨论的，那个系统可能已经不存在了，对吧？
And that's what we were talking about before, that the system may no longer be there, right?
雌激素受体的结合方式，可能不再像你仍处于生育期、仍处于向非生育期过渡时那样发挥作用。
The estrogen receptor binding may not be working the way that it does once you still are reproductive, once you're still transitioning to your non reproductive life.
当你已经过了二十年后，它可能
When you're, you know, twenty years past, it may
根本不起作用了。
just not work.
你就像在敲一扇紧闭的门。
You're bouncing off of a closed door.
是的。
Yeah.
这个说法很贴切。
That's a good way to put it.
而且，这些制剂也与正确的那种不同。
And also, those are different formulations to what Right.
现在会使用的那一种。
The one would use now.
是的。
Yes.
而新的制剂从未以这种方式进行过测试。
And the new one, the newer formulations have never been tested this way.
对。
Right.
所以我们不能泛化。
So we cannot generalize.
我们也不能将结论推广到阿尔茨海默病，因为那不是研究的终点。
And we also cannot generalize to Alzheimer's because that was not the endpoint.
终点。
The endpoint.
好的。
Alright.
丽莎，如果我现在给你十亿美元，你会做什么样的研究？
Lisa, if I gave you a billion dollars right now, what study would you what would be the study?
我会重做女性健康倡议记忆研究。
I would redo the Women's Health Initiative memory study.
我会针对阿尔茨海默病的生物标志物开展研究，对象是处于中年、经历更年期并接受激素治疗的女性，特别是使用微粒化雌二醇和孕酮——这些更接近人体自然产生的激素，并通过脑部扫描来确定所需的剂量，不仅为了缓解症状，更是为了脑部健康和支持。
I would do it using biological markers of Alzheimer's where we work with women who are in midlife, are going through menopause and they're taking hormone therapy, especially micronized estradiol and progesterone, which are closer to what their bodies naturally produce, dosed using brain scans so that you can know what kind of dose you actually need, not just for symptom relief but for brain health and support.
我会使用阿尔茨海默病的生物标志物，因为这样可以在治疗过程中进行追踪。
And I would use biological markers of Alzheimer's because that I can track as you get treated.
什么是生物标志物？
What is a biological marker?
这些就是脑部扫描。
So, these are It's the brain scan.
我们可以观察大脑中的斑块、神经纤维缠结，也可以观察雌激素以及治疗如何影响雌激素在大脑中的结合。这项研究的核心是什么？
So, we can look at plaques in the brain, we can look at tangle formation in the brain, we can look at estrogen and how the therapy modifies estrogen binding in the brain What's in your the of this study?
你的假设是什么？
Your hypothesis is?
但我的假设是乐观的，顺便说一下，我也会准备各种B计划，因为这些方法可能不会成功，但我认为我们应该给它们一个公平的机会，因为为什么你不
But my hypothesis is optimistic, of course, by the way, I would also have all sort of plan B in place because there is a chance that they may not work out, but I think we need to give it a fair chance because why don't you have
为这项研究提供一百万美元呢？
a million dollars for this study?
我有五千万。
I have 50,000,000.
但让我给你看看观察性研究，因为我们有二十年的临床前研究证据表明，在更年期左右开始的激素疗法对大脑具有保护作用。
But let me show you the observational research because we have twenty years worth of evidence from preclinical studies that hormone therapy started around the time of menopause is brain protective.
我们也有观察性数据表明了类似的结果。
And we have observational data showing something similar.
但观察性数据无法证明因果关系。
And observational data cannot prove cause and effect.
你需要进行临床试验，而这正是我们所缺失的。
You need to have clinical trials, which is what we are missing.
但即便如此，我们确实看到，对于接受过子宫切除术或卵巢切除术的女性，仅使用雌激素疗法与阿尔茨海默病风险降低百分之三十相关。
But nonetheless, we do see that estrogen only therapy is associated with a thirty percent reduced risk of Alzheimer's disease among women with hysterectomy and or oophorectomy.
而对于雌激素联合孕激素，我们目前还无法通过观察性数据区分孕酮与合成孕激素，但仍有风险降低的趋势。
Whereas estrogen with a progestogen, we can't yet separate progesterone to progestin with observational data, but there's still a trend towards a risk reduction.
这并不意味着每位女性都需要服用激素来降低阿尔茨海默病的风险。
This does not mean that every woman needs to take hormones reduce the risk of Alzheimer's.
这意味着我们确实需要开展相关研究。
It means that we do need to do the research.
我们最近的一项发现非常有趣，而且这一结果已被重复验证。
And something that we showed just recently that I think is really interesting is that also was replicated.
地理位置具有显著影响。
There's a strong effect of geographic location.
如果你查看所有研究，比如在北美，所有数据都是蓝色的，表明绝大多数研究显示了保护性效应。
So if you look at all the studies, like in North America, everything is blue, it means that the vast majority of studies show a protective effect.
北欧地区则呈红色。
Northern Europe is red.
没有保护作用。
Not protected.
没有保护作用。
Not protected.
为什么？
Why?
我们不知道。
We don't know.
但那里确实存在某种因素。
But there's something there.
可能是使用的激素制剂类型、诊断标准，或者有多种原因。
It could be the kind of hormonal formulation that was used, the diagnostic criteria, it could be a number of reasons.
但北美地区的研究始终显示有保护作用，尤其是在加拿大，这强烈表明我们需要研究不同人群在临床使用这些制剂时的具体做法。
But the studies in North America are consistently protective in Canada, which really suggests that we need to look at what different people are doing clinically when they use these formulations.
很好。
So good.
我想说的是，当人们做出诸如‘你需要接受激素治疗来预防痴呆’这样的笼统声明时，我们其实并不确定。
I just want to say this, when people say blanket statements like, You need to go on hormone therapy to prevent dementia, we don't know.
我们需要开展研究。
We need to do the research.
但当人们说——我经常听到这种说法——没有证据表明激素疗法可以预防——
But when people say, which I hear, there is no evidence that hormone therapy prevents-
就在一个月前的全国会议上有人这么说。
This was said at a national meeting just a month ago.
是吗？
Oh, yeah?
我其实是在社交媒体上看到的。
I heard it on social media actually.
这可能会被误解。
It could be misinterpreted.
这其实和我们说需要开展研究是一个意思。
It's kind of saying the same thing that we need to do the research.
我们需要付诸实践。
We need to do the work.
我认为，人们理解的是——请纠正我，英语是我的第三语言——已经做了正确的研究，但没有发现益处。
What people understand, I believe, correct me, English is my third language, understand is that the right research has been done and there was no benefit.
这就是我的理解。
This is what I understand.
没有证据表明它有效。
There is no evidence that it works.
我认为更准确的说法是，我们尚未开展正确的研究。
What we could say that I think is more accurate is that we have not done the right research yet.
我们不知道它是否有效，但同样也真的不知道它是否无效。
We don't know if it works, but we also really don't know that it doesn't.
这一点很重要，因为这是我们能够检验的。
And that's important because it's something we can test.
比如，我们可以检查它对某些女性有效，而对其他女性无效。
Like, for instance, we can check whether it works for some women and not others.
可以检查它
Can check if it
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