188 | 原发性进行性失语症（PPA）——与艾米丽·罗加尔斯基博士的对话

我只是想澄清一下。

Just want to clarify that.

你能简单总结一下目前在PPA中可用的最新生物标志物吗？有没有什么即将出现的新进展？

Can you give us a brief summary of the most up to date biomarkers that are available in PPA and maybe if there's anything on the horizon?

当然可以。

Sure.

目前最可靠的生物标志物，还是集中在阿尔茨海默病这一块。

So the robot most robust biomarkers that we have still live in the the land of Alzheimer's.

针对阿尔茨海默病的病理，我们现在已经有脑脊液生物标志物了。

So for Alzheimer's neuropathology, we now have CSF biomarkers.

还有PET成像标志物，比如淀粉样蛋白PET和tau蛋白PET。

We have PET biomarkers that come in the form of amyloid PET and tau PET.

这些标志物在患有遗忘型表现或有阿尔茨海默病风险的人群中已经被充分验证，极大地改变了临床试验的格局，让我们能把对的病人放进对的试验里。

And those have been, you know, robustly characterized in individuals with an amnestic phenotype or who are at risk for an amnestic phenotype due to Alzheimer's disease and have been immensely helpful in changing our clinical trial landscape so that we get the right patients into the right trials.

我的意思是，有些人确实表现出遗忘型综合征，但病因可能根本不是阿尔茨海默病。

And by that, I mean, actually having someone present with an amnestic syndrome, but it may not be due to Alzheimer's disease.

所以一开始，确保招募的失忆综合征患者确实存在阿尔茨海默病的神经病理改变，这一点至关重要。

And so ensuring that you're enrolling individuals with an amnestic syndrome who actually have, Alzheimer's disease neuropathology is incredibly important at the outset.

这些生物标志物已经开始在原发性进行性失语症中得到验证，我们发现了一些有意思的现象。

These biomarkers have started to be validated in primary progressive aphasia and we've seen that, you know, a few interesting things.

我们团队亚当的研究表明，虽然我们通常认为阿尔茨海默病中的淀粉样蛋白PET是整个大脑同时出现的，但在原发性进行性失语症中，我们发现左侧的淀粉样蛋白沉积明显多于右侧——至少在那个‘恰到好处’的阶段是这样。

Work by Adam in our group has shown that although we think of amyloid PET as in Alzheimer's disease as sort of appearing across the brain all at once, we've shown that there is some clinical relationship between that can be seen of, with amyloid PET biomarkers in primary progressive aphasia where the left side shows more amyloid burden than the right side at least kind of in that Goldilocks phase, if you will.

Tau蛋白PET则特别有助于定位这些蛋白异常沉积的具体位置，它与命名障碍或其他语言损伤的相关性，比淀粉样蛋白标志物更强。

Tau PET biomarkers are also particularly helpful for looking at spatially where where these proteinopathies are, and they show a stronger correlation with naming or other language impairments compared to to amyloid biomarkers.

当然，最紧密的关联还是在于脑萎缩，这也很合理，毕竟我们一直认为的‘杰克曲线’就是这么描述病理进程的。

Of course, the tightest relationship seems to still be with atrophy, and that makes sense when we think about the the Jack curves of the ordering of which things are, hypothesized to happen.

先是淀粉样蛋白变化，接着是PET异常，最后才出现脑萎缩。

So changes in amyloid followed by changes in PET, and then, result in atrophy.

这些关系在原发性进行性失语症中似乎也存在，但还需要更多验证。

So those relationships seem to exist in PPA, but could use additional validation.

当然，最新登场、让所有人兴奋的，是血液生物标志物——它们正变得越来越有用，也越来越可靠。

The newest players to the game, of course, are, and the excitement for everyone is the possibility of these blood based biomarkers that again are becoming more and more useful and more and more reliable.

所以我觉得我们现有的阿尔茨海默病生物标志物已经相当可靠了，关键是要把它们用在PPA患者身上，推动把这些患者纳入针对阿尔茨海默病病理的疾病修饰型临床试验。

So I think our Alzheimer's biomarkers are quite robust and the advocacy there is to use them for individuals with PPA and to advocate for their inclusion in farm trials where the target is disease modifying trials for Alzheimer's disease neuropathology.

但很多时候，他们却被排除在外。

And oftentimes they are excluded.

而且因为PPA本身太罕见了，专门针对阿尔茨海默病的试验本来就很少。

And then rarely because PPA is so uncommon, there have not been AD specific trials.

他们被排除的一个原因，是有些终点指标对PPA患者来说根本不适用。

One of the reasons they've been excluded is because sometimes the endpoints don't make sense for PPA.

比如可能会用记忆能力作为主要终点，或者指标更偏向于记忆功能。

So there may be a memory endpoint or an endpoint that is more heavily weighted towards memory.

所以试验设计者可能就因此觉得PPA患者不适合入组。

And so then it can be that would be a reason that the trialists may not include PPA.

但我个人坚信，我们得动脑筋，想办法让这些患者也能参与进来。

But there my my belief is that we should really think about ways to creatively include these individuals.

好消息是，他们已经出现在一些新获批药物的适当使用标准里了，这真的很让人振奋。

And and so they have been a part of some of the appropriate use criteria for the the newer medications that have been approved, which is exciting.

但要弄清楚这些疗法在PPA患者中的疗效和实际效果，还有不少工作要做。

But there's still work to be done to understand efficacy within PPA and effectiveness.

感谢你为PPA患者发声，这太重要了。

Appreciate your advocacy for the patients with PPA, as needed.

我们刚才聊了很多PPA和阿尔茨海默病之间的异同。

So we've been talking about overlap and differences between PPA and Alzheimer's disease throughout the conversation.

我想简单总结几个关键点，方便听众理解，然后看看你还有没有要补充的，再往下走。

I just wanna list a few of the key findings to make it easier for listeners and then see if you have anything else to add before we move on.

就像我们多次提到的，语义型PPA通常由阿尔茨海默病的病理引起，大致来说，是左脑或语言优势半球的颞顶区域。

So as we said several times, logopenic PPA typically due to Alzheimer's disease, neuropathology, roughly speaking, left or language dominant temporal parietal area.

阿尔茨海默病痴呆和语义型PPA的临床表现，在一定程度上是重叠的。

The clinical syndromes in Alzheimer's disease dementia and logopenic PPA can overlap to some degree.

如果我们从更广的角度看PPA和阿尔茨海默病的区别，PPA的发病年龄通常更早。

If we step back and think about PPA broadly versus Alzheimer's disease, PPA tends to have an earlier age of onset than AD.

总体来说PPA比较少见，而且男女发病率差不多，但阿尔茨海默病在女性中更常见。

It's less common overall and unlike AD, has roughly an equal prevalence in women versus men, whereas in Alzheimer's, it's more common in women.

正如我们所料，阿尔茨海默病患者的非语言记忆受损更常见，而且风险因素也有些不同。

As we might expect, nonverbal memory is more likely to be impaired in Alzheimer's disease versus PPA, and there are somewhat different risk factors.

这些我们之前聊过一些。

We've talked about some of these.

APOE基因的e4等位基因会增加患阿尔茨海默病的风险，但据我所知，对PPA的影响没那么大。

So APOE, the e four allele increases the risk for Alzheimer's disease, but not so much for PPA to my understanding.

你之前提到过，艾米莉，有学习障碍家族史的人，得PPA的风险比得阿尔茨海默病更高，看起来是这样。

While you had mentioned earlier, Emily, a family history of learning disorder is a risk factor for PPA more so than for Alzheimer's disease, it seems.

我想知道，你有没有其他想补充的？特别是从临床角度，什么时候区分这两者特别关键？

I'm curious if there's anything else you'd like to say about comparing the two, maybe in particular from a clinical standpoint when, in what circumstances is it really important?

其他时候，除了我刚才说的那些因素，我们可能还真没法百分百确定是语义型PPA还是普通的阿尔茨海默病。

In other times, we might not know for sure if it's a logopenic PPA versus standard Alzheimer's disease aside from the factors I just mentioned.

是的。

Yeah.

你已经把主要的异同点都说全了。

I think you've had on on most of the key similarities and differences.

我觉得与其纠结具体是哪种亚型，不如重点看他们有没有语言能力明显下降，而其他认知功能相对保留这些核心特征。

I think I would focus just on less on on what particular subtype, but just focus on do they have those core features of language loss and relative sparing of other cognitive domains.

另外，原发性进行性失语和阿尔茨海默病患者有一个共同点，就是绝大多数都是散发性的。

The other thing that both individuals with primary progressive aphasia and Alzheimer's dementia share is that they're both most commonly sporadic.

这两种病的遗传因素都很少见。

So the genetic causes for both syndromes are very small.

对。

Right.

你刚才提到病程时间线，确实，语言问题出现的先后能帮我们区分这两种病。

And you mentioned the timeline, you know, the language issues could make a difference in parsing them out.

比如，如果语言障碍先于记忆问题出现，那更可能是PPA；要是记忆问题先于语言障碍，那更倾向于是阿尔茨海默病。

Like if the language issues predate the memory problems, we're typically looking more PPA versus if the memory issues predate the language for Alzheimer's disease.

不过说到底，这还得靠患者自己说或者家属提供信息，但这些往往不太靠谱。

Again, you're relying on self report or collateral report, which is not the best often.

也许吧。

Maybe

我再补充一点，因为病人走进诊室时，通常会说：‘我记性不好了。’

I'll say one other thing there, because what commonly happens when individuals walk into the clinic is they're going to say, I have a memory problem.

我老是想不起该说什么词。

I'm losing my words.

是的。

Yeah.

这时候你就得接着问：‘能具体说说吗？’

And that is the cue to say, can you tell me more about that?

要弄清楚，到底是记不住东西，还是根本找不到合适的词？

To understand, is it truly a retentive memory challenge or is it that they can't find their words?

所以病人的自述特别重要，但你需要有敏锐的临床直觉，才能听出来：你说的‘记性差’，是不是指‘老想不起词’？

But so the self report is so important, but it takes that really astute clinical ear to say, oh, wait, when you say memory, I'm having trouble remembering my words.

这算语言问题吗？

Is that language?

还是算记忆问题？

Is that memory?

接下来这些问题能帮我们理清这一点。

And those next questions kind of help to disambiguate that.

我们之前提到过，阿尔茨海默病痴呆通常发生在老年人身上，尤其是晚发型。

I think we touched on a little bit that Alzheimer's dementia tends to be older, at least the late onset form.

但现在我们越来越意识到，早发性痴呆——特别是阿尔茨海默病——也越来越常见。

Now we're starting to recognize more and more that there are early onset forms of dementia, and and particularly Alzheimer's dementia.

早发年龄让患者确诊原发性进行性失语症变得特别困难。

The early onset age has made it really difficult for individuals to get a diagnosis of PPA.

这既跟语言能力的变化有关，也跟发病年龄太早有关。

So it's both the changes in language and the early onset nature.

可惜的是，患者往往要花上好几年，而不是几个月，才能得到确诊。

It still unfortunately takes people years rather than months to receive a diagnosis.

通常得跑好几家医院、反复就诊，甚至还要跨省求医。

And commonly the journey requires multiple doctors, multiple visits, many times out of state.

从医疗公平和可及性的角度看，这正是导致我们很难搞清原发性进行性失语症真实发病率的原因之一——很多病例根本没被发现，因为患者跑去看病，医生却说这是抑郁症。

And so if we think about that from a equity, and access to care, and this is one of the drivers that makes it difficult to really understand how common PPA is, is that I think we're missing some diagnoses in cases because you have to be someone who says, I went to the doctor and they told me it was depression.

你得是个特别坚持的人，才会说：这根本不是抑郁症。

You have to be someone who's got enough persistence to say it wasn't depression.

我得再回去，继续找答案。

I need to go back and find more.

这也不是压力造成的。

It wasn't stress.

不对劲，这事儿哪儿不太对。

It wasn't, this isn't quite right.

所以，要拿到这个诊断，往往得同时具备知识、毅力和经济能力，三样缺一不可。

And so it's both the education, the persistence and the financial means often that you have to have all three to persevere to get this diagnosis.

这依然是个大难题，但希望未来生物标志物能帮上忙。

And so I think that is still an area of challenge a space where hopefully biomarkers will start to help us.

我们还没细说，但像NFL这样的指标虽然不够特异，却能提示可能存在神经退行性病变。

So we didn't fully touch, but things like NFL that have, that are more nonspecific, but can start to hint at whether there's a neurodegenerative process.

如果我们能更多地用上这些工具，帮助患者从全科医生快速转诊到专科，早日确诊，对摸清PPA的真实发病率、缩短诊断周期就太关键了。

But the more that we have those so that we start to help individuals get from primary care to specialty clinics or to be able to make this diagnosis more rapidly will be really important for understanding the prevalence of PPA and for reducing that amount of time.

等他们最终确诊时，都已经精疲力尽了。

People are so exhausted by the time that they get this diagnosis.

这真的太难了。

It's just incredibly challenging.

是的。

Yeah.

我觉得提高认知度会有帮助，不管是对医生还是对普通大众，毕竟这病大家都不太了解。

I think increasing awareness will help to some degree in both among practitioners because it's not widely known, and among the general public.

我觉得布鲁斯·威利斯家人公开这件事，大大提升了大家的关注。

I think Bruce Willis' family coming out helped with the awareness quite a bit.

那之后，我听到好多人在讨论这个病了。

I've heard people talking about it more after that happened.

我也能理解医生为啥难确诊，毕竟这病少见，而且特别复杂。

It also, I mean I feel I understand why practitioners would struggle to diagnose it because it is relatively rare and it is complex.

你得赶在那个刚好的时机抓住病人，就像你之前说的——病情已经明显到能看出来，但还没糟到一切都乱成一团。

You have to catch somebody in the Goldilocks zone like you mentioned where they're far enough along that you can see real changes, but they're not too far along when everything is just muddied.

随着病情发展，阿尔茨海默病和原发性进行性失语症患者都会出现语言和记忆问题，诊断起来确实复杂，但公平性我们始终得放在心上，越重视越好。

They have both language and memory problems as the disease progresses in both Alzheimer's and PPA in general, so it does get complicated to to diagnose, but equity is always something that we should be aware of and increasing as much as possible.

还有另一点对神经心理学家特别相关，我们之前也提到过——

One other piece of this that's relevant for neuropsychologists, as we've talked about

就是临床访谈，要关注语言和记忆变化的早期迹象，测试选择我们稍后再聊。

the clinical interview, the early history of changes in language versus memory, and we'll talk about test selection a bit later.

在我看来，行为观察对这类语言障碍特别关键。

Behavioral observations, in my opinion, are so important with these language syndromes.

我们跟患者聊天时，能识别出原发性进行性失语症的一些表现，这真的特别有帮助，尤其是在早期阶段，想尽早发现、及时支持患者获得治疗，这就是个好例子。

So for us, experience in conversing with a patient and recognizing what some of the PPA symptoms look like, I think can be incredibly helpful, especially in these the early stage where we're trying to identify it and support our patients and getting care as just one example.

我们总说‘语法缺失’，之前也提过，大家都知道语法是什么，但具体表现起来挺专业的。作为临床医生，得靠经验积累，才能真正识别出来，这点太重要了。

Agrammaticisms, we throw that word around, we talked about it already, but we all know what grammar is, but what that looks like can be technical and they're, you know, having experience, building experience and detecting it as a clinician, I think is incredibly important.

比如患者漏掉功能词、说话像电报一样、句法出问题这些情况。

Stuff like people omitting function words, telegraphic speech, problems with syntax.

你们听我们说话的时候，大概率觉得我们语法和句式都挺正常的，但那些患有‘非流利型’语法缺失的患者，他们的表达就完全不是这样了。

So as listeners are are hearing us, hopefully for the most part, we are using appropriate grammar and sentence structure, somebody with the agrammaticisms that you might see in the quote unquote non fluent variant.

比如，他们不说‘我妈妈去超市了’，而只说‘妈妈，超市’，把功能词都省掉了。

As an example, instead of saying, you know, my mom went to the grocery store, they might say, mom, grocery store, omitting function words.

艾米丽，如果你觉得有帮助，也可以再补充几个例子。

And Emily, you're welcome to add more examples if it's helpful.

我还想强调一下，行为观察真的特别关键，这得靠积累经验才能慢慢练出来。

I I also just wanna make the general statement about how critical behavioral observations are, which we get good at identifying through building experience.

说得对。

Yeah.

我完全同意。

I couldn't agree more.

而且，真听到几个病人的实际对话，才能一下子明白过来——毕竟语言太复杂了，有这么多专业术语和特征。

And having the opportunity to kind of hear example patients really goes a long way that helps it click because all of these words, you know, language is complex and it does have all of these technical features.

所以，举些实际例子，我觉得是最能帮人真正理解这些表现的方式。

And so giving those examples are is the I think the best way to to really help solidify some of the aspects that you might hear.

既然阿尔茨海默病和语义性PPA有这么多重叠，你觉得语义性PPA算不算阿尔茨海默病的一种语言亚型？你怎么看？

Given all the overlap between Alzheimer's disease and logopenic variant PPA, Would you consider logopenic PPA like a language variant of Alzheimer's disease, or what do you think about that?

没错。

Yeah.

所以我会说，带有阿尔茨海默病生物标志物升高的PPA。

So I would say PPA with elevated AD biomarkers.

在文献里，我们管这叫阿尔茨海默病的失语型，就是强调患者有失语症状——我们先定义这个临床表现，再搞清楚背后导致它的病理机制。

In publications, we've called it the aphasic variant of AD, just referring to the fact that they have an aphasia, so that clinical syndrome, defining that clinical syndrome and then defining the underlying pathology that's causing it.

就像你嗓子疼去看医生，那是症状，但你不知道是扁桃体发炎、链球菌感染、昨晚看球喊太猛了，还是普通感冒或病毒引起的。你去看医生，就是为了搞清楚到底啥原因引起的，能不能治，还是回家躺平就行。

So just like you would go to the doctor if you had a sore throat, so that would be the symptom, but you didn't know whether you had tonsillitis or strep throat or you had yelled too much at the football game last night or, you know, some other just bad cold or virus, but we go to the doctor to disambiguate what is causing my symptoms and am I eligible for treatment or do I just need to go home and sleep?

同样的道理，我们用‘由阿尔茨海默病引起的进行性失语’或者‘阿尔茨海默病的失语型’这种说法，其实意思差不多，可以互换。

In the same way, using that clinical marker of calling it primary progressive aphasia due to AD, aphasic variant of AD, I think these are relatively interchangeable.

‘阿尔茨海默病的语言型’也属于这一类，因为它描述的是当你知道病理基础时——不管是通过活体生物标志物，还是通过尸检发现的——那些和临床综合征直接相关的神经病理特征。

Language variant of AD would fall in that same realm because it's describing the neuropathology when you know that information either from in vivo biomarkers or from individuals who have have come to autopsy and those are the the primary neuropathologies associated with their syndrome.

趁现在想起来，我想趁这个机会跟Emily说声谢谢。

I wanna take this opportunity while I'm thinking about it to say, thank you, Emily.

我知道这事儿有多复杂，我们之前也聊过，有你这样的专家带我们理清PPA和其他疾病之间那些没完没了的关联和多样性，真的太有帮助了。

I know this is we've talked about how complicated this is, and so it's so helpful to have an expert to walk us through all of the endless complexities in terms of PPA's relationship to other disorders, the heterogeneity.

这真的太有帮助了。

This is incredibly helpful.

在前面这些铺垫的基础上，再引入更多复杂性，我想聊聊PPA和行为变异型额颞叶痴呆之间的重叠，尤其是神经精神症状这块。

With that prelude, bringing in more complexity, I wanna touch on the overlap between PPA and behavioral variant FTD, particularly related to neuropsychiatric symptoms.

你之前提到过孤独、抑郁和焦虑这些情况。

You had alluded to this earlier talking about loneliness, depression, anxiety.

有时候我们会想，这些症状到底是患者对神经疾病的一种适应性反应，还是说它们本身就是由神经病理直接破坏了相关脑回路引起的？

Sometimes we think about are those symptoms quote unquote secondary to adjustment to a neurological illness or are they quote unquote primary as in the neuropathology is directly affecting neural circuits that is causing them.

我们常常很难分清这些症状到底是原发的还是继发的。

We often might not be able to disentangle whether it's primary or secondary.

但不管怎样，额颞叶痴呆确实可能和PPA重叠，所以PPA患者也可能出现神经精神症状，我很想听听你的看法。

Regardless, FTD, you know, can overlap, and so you can have neuropsychiatric symptoms in PPA, and I'm interested to hear you talk about that.

是的。

Yeah.

我觉得这真的特别复杂，因为随着疾病进展，出现这些神经精神症状确实很合理。

And I think it's incredibly complex, because it it certainly makes sense that as that disease moves, you may be more likely to have these neuropsychiatric symptoms.

这还跟具体情况有关，你说是鸡生蛋还是蛋生鸡呢？

It also can be situational of if you, you know, what is the chicken or the egg?

你开始退缩，慢慢跟社会脱节。

You start to withdraw, and become socially isolated.

然后抑郁也就跟着来了，跟其他问题搅在一起。

And then that is, then you also have depression that comes in the mix there.

是因为你对自己说话不自信，还是这些因素根本就分不清？

Is that because you are just uncomfortable with your language or are these things all mixed up together?

我觉得这真的很难理清楚。

And I think that's an, it's very, very difficult to disambiguate there.

很可能两种情况都有，得看每个人的具体情况，关键是弄清楚这些症状最早是从哪儿冒出来的，然后才能考虑用什么药更有效。

And probably because there's some of both and it's going to depend on the individual and really understanding where those symptoms start to first emerge and then pharmacologically what might be helpful, in that space.

所以我觉得这其实引出了另一个重点——针对原发性进行性失语的照护，必须靠团队协作。我经常去社区做讲座，讲讲‘你的照护团队都有谁’。

And so I think this really speaks probably to another important point and that's the team approach to care for primary progressive aphasia is that I will often give, you know, community lectures and talk about, you know, who's your care team.

你可能想不到，团队里的人会这么多，而且在你病情发展的不同阶段，不同角色的重要性也会变化。有时候，特别需要法律团队介入，提前规划未来。

And it may be a lot more people that you think, and some of those individuals are going to play a more prominent role at different points in your disease journey, in your symptom journey where there are times where it's gonna be really important to work with a legal team and think about planning for the future.

其他时候，就得让神经精神科医生参与进来，帮我们分清哪些症状该用哪种治疗，是该优先考虑语言治疗或职业治疗，还是别的办法。

Other times, it's gonna be really important to have those neuropsychiatrists in the mix so that they can help disambiguate and and sort out treatments that might be most appropriate for particular symptoms that individuals are experiencing versus our speech language therapy and occupational therapy colleagues.

我觉得社工就像是天使，把这一切都串联了起来。

I think social workers are the angels that help to bind a lot of this together.

我常听到的第一个建议就是：确诊之后，别光顾着高兴，还得接着走下一步。

And so it's often the first recommendation I get is like once you, you know, having a diagnosis is important.

别忘了神经科和神经心理科的同事，但社工或者护理协调员才是关键的桥梁，他们帮你规划整个治疗团队，知道什么时候该拉谁进来，什么时候该暂时放一放，看你现在走到哪一步了。

Don't forget about your neurology and neuropsychology colleagues, but those social workers are often, or care navigators are the key connectors to helping you think about building out the rest of your care team and who needs to kind of be dialed up in this moment or dialed back depending on where you are in the journey.

是的。

Yeah.

完全同意。

Fully agree.

虽然行为变异型额颞叶痴呆和原发性进行性失语的神经精神症状有不少重叠，但也存在一些区别。

And although there are a lot of overlaps in the neuropsychiatric symptoms between behavioral variant FTD and PPA, there are some differences.

对吧？

Right?

所以额叶变异型FTD，主要表现为性格改变、社交行为异常、怪异举动，还有执行功能方面的困难。

So the BV FTD, we're looking at more personality changes, social comportment issues, odd behavior, executive functioning difficulties.

我还想顺便澄清一下，对于……

Just wanted to also clarify that for

没错，这点说得特别好。

Yes, those That's a great clarification point.

如果病情发展，从原发性进行性失语症（PPA）逐渐波及到额叶，确实可能出现和额叶变异型FTD非常相似的症状。

Now it can be possible that if the disease moves towards your you have a diagnosis of PPA and the disease spreads toward the frontal lobe, you can get those overlapping really prominent syndromes or symptoms that you see in BVF TD.

所以这点很重要——和你的医疗团队密切配合是关键。

And so that's important to note that that can happen and really working with your care team is essential.

对PPA患者来说，更常见的症状其实是抑郁。

I think more commonly would be depression as a symptom that may be experienced by individuals with PPA.

不过一开始，额叶变异型FTD患者最明显的体验，确实是判断力和行为上的巨大变化。

But certainly, initially, the lived experience of someone with a a diagnosis of BVF TD are gonna be those, yeah, prominent changes in judgments.

比如有人会去超市，突然抱住一个完全不认识的收银员——这在我们这儿可完全不合社交规范。

And so that can manifest, that someone goes to the grocery store and hugs the grocery store clerk that they do not know, which is out of the social norms, in this country.

说到不同语言和不同诊断方式的时候，这也是个值得注意的点。

And that's another thing to point out when we were talking about different languages and different ways that these diagnoses are made.

文化规范起着关键作用，而且全球各地的规范都不一样。

Cultural norms play an important role, and and those norms differ globally.

在一个国家算异常的行为，在另一个国家可能再正常不过了；但在这里，BBFT患者常常会出现这类变化——比如本来内向的人突然变得特别外向，超出了社会常规的界限。

So what is abnormal for one country may be distinctly normal in another, but in this setting, commonly individuals with BBFT will report changes like that or someone who is one shy is now quite outgoing in a way that stretches beyond the borders of social norms.

有些人还会陷入一种仪式化的重复行为，比如在院子里数蚂蚁，一数就是好几个小时。

Individuals can also become kind of ritualistically focused on counting certain things like amps in the yard, for hours and hours on an end.

这些也都是比较常见的表现。

And so those are those are other common manifestations.

是的。

Yeah.

这很有帮助。

That's helpful.

我们之前跟布鲁斯·米勒聊过BVFTD的事，会在片头跟听众提一下，简单回顾一下行为变异型FTD的核心诊断标准：行为失控。

We spoke to Bruce Miller a while back about BVF TD, and we will have mentioned that in our intro for our listeners, to briefly review core criteria of behavioral variant FTD would be behavioral disinhibition.

我们之前聊过早期的冷漠、迟钝，还有共情能力的丧失，这些都可能非常明显，还有那种强迫性的刻板行为。

We've been talking about very early apathy or inertia, loss of sympathy or empathy that can be very prominent, compulsive ritualistic behavior.

你刚刚提到的那些，其实也属于这一类。

You were just referring to some of that.

艾米丽，还有过度口腔行为和饮食习惯的改变。

Emily, hyperorality, dietary changes.

所以你看，行为变异型FTD在最早期就这么明显了，这正是它和PPA区分开来的关键，虽然两者确实会有重叠。

So this is, I'm sure, emerging how behavioral BVF TD is in the earliest stages, which is a way to differentiate it from PPA, although they can overlap.

咱们现在换个话题，聊一个相对新一点、但很多听众都会特别感兴趣的内容——针对PPA患者的评估和测试选择，特别是神经心理学家如何评估语言能力。

Let's take a moment and, move into a relatively new topic, which many of our listeners will be very interested in, which is assessment and test selection for patients with PPA for neuropsychologists, specifically assessing language abilities.

这里头有好几套多维度的失语症评估量表可用。

So we have multiple multi domain aphasia batteries that are relevant here.

比如波士顿诊断性失语症检查（BDAE）、多语言失语症检查（MAE），还有西方失语症量表（WAB），以前我们都这么叫。

The Boston Diagnostic Aphasia examination, BDAE, the Multilingual Aphasia examination or MAE, the western aphasia battery or as we used to call it the WAB.

再细一点，我们可以专门挑一些语言功能来测试，帮助我们更精准地判断患者的失语类型。

Drilling down further, we can think about specific components of language to test to help us characterize our patients aphasia syndrome.

我们之前聊过这个。

We talked about this earlier.

不管你一开始对亚型有什么猜测，都得对语言能力做全面评估。

It's important to do a thorough assessment of language irrespective of your early hypothesis about the subtype.

我们可以看看这些测试：言语表达、图片命名、复述、词义理解、物体知识、语法理解和产出、阅读障碍比如表层失读症、书写障碍比如失写症，还有其他的。

So we can think about tests of speech production, confrontation naming, repetition, word comprehension, object knowledge, production, comprehension of grammar, reading deficits like surface dyslexia, writing deficits such as dysgraphia, and others.

Emily，你对我们有什么临床建议吗？

So what are your clinical recommendations for us, Emily?

对。

Yeah.

不妨想想，我们为什么选这些测试，而不是别的？

So it's probably good to think historically of like, why do we use these tests and not others?

你提到的这些确实都相关，不过得打个补丁——我们用的大多数工具，原本是为其他综合征设计的。

And I think all of the ones that you mentioned are relevant, but maybe just like a small asterisk that most of the time we're borrowing measures that are used and were created for different syndromes.

现在只是被我们拿来用在这里了。

And we're applying them here.

所以这些测试都有些局限，比如西方失语症成套测验本来不是为原发性进行性失语设计的。

And so they all come with little caveats that, you know, the Western Aphasia Battery was not designed for PPA.

它其实是为中风引起的失语和其他类型开发的。

It was really came about, you know, more for stroke based aphasia and other syndromes.

这套测验里有些倾向性，会把某些缺陷放大得更明显。

There are leans in that one that are gonna amplify certain deficits more than others.

所以对神经心理医生来说，最难的是别光看分数，得真正理解患者是怎么回答的、表现如何。

So it really is a difficult job for a neuropsychologist to not rely strictly on the scores, but really to understand performance, and how individuals are are answering these, and how they're how they're performing.

像波士顿命名测验、MINT，或者其他物体命名测试，还有西北大学命名量表，这些都能用。

So the the Boston naming tests or the Mint, things like that can help other object naming tests, the Northwestern naming battery.

还有费城命名测试之类的，专门用来评估命名障碍或物体命名能力。

There have been others that have, you know, Philadelphia naming test that help to assess anomia, or object naming.

过去我们还借用过PPVT里的一部分题目，用来测词汇理解。

There are tests that we've borrowed, in the past, like the subset of items from the PPVT that can help assess, word comprehension.

金字塔与棕榈树测试对评估物体认知挺有帮助的。

Pyramids and palm trees can be helpful for object knowledge.

《灰姑娘》的故事对分析句子生成和流畅性很有帮助。

The Cinderella story can be helpful, for really thinking about sentence production and fluency.

不过这主要用在研究里，因为从这测试里得出的指标，临床里没法马上打分。

Now this is mostly used in research settings because the measures that come out of that are not things that you're going to immediately score in in clinic.

还有，就像你提到的，像PALPA这种针对表面型失读和失写症的工具。

And then, you know, as you mentioned, you know, measures like the PALPA for surface dyslexia and dysgraphia.

现在也有一些新工具正在出现，有些在神经退行性疾病，特别是PPA患者中的常模数据越来越好了——比如UCSF团队多年研究的‘Tab Cat’。

But there are new batteries that are emerging and some of them have been better are are starting to be better norms in neurodegenerative populations and and PPA, particularly, you know, the UCSF group has been working for years on the tab cat.

就是想通过计算机化手段，捕捉日常生活中自然发生的语言变化。

So thinking about computerized measures and getting measures of naturalistic changes in in everyday life.

所以我觉得，就像整个神经心理学领域都在进步一样，PPA领域也一定会从中受益。

So I'm excited to just as it's emerging in the field of neuropsychology in general, I think PPA will also benefit from these changes that are occurring across the field.

如果你是为了继续教育学分在听，第二个关键词是‘静脉’。

If you're listening to this for CE credits, the second code word is venous.

静脉。

Venous.

谈谈原发性进行性失语症中临床表现与病理关联的实用价值。

Talk about the clinical utility of a clinical pathological correlation in PPA.

我们刚才已经提到过，比如神经病理学、蛋白沉积类型、病变在脑中的位置，同时我们也讨论了综合征层面的症状、测试结果——当我们面对一个具体患者时，会有脑部MRI，可能还有PET或脑脊液等生物标志物，再加上神经心理评估、行为观察和测试数据。

So we've been touching on this, the neuropathology, the proteinopathies, where in the brain, and then we're also talking about more syndromically the symptoms, the test profiles as we see an individual patient and we have brain MRI, potentially biomarkers like PET or CSF, and then we also have neuropsych eval behavior observations, test data.

你能分享一些临床经验，告诉我们怎么把这些信息整合起来，更好地帮助患者吗？

Can you give us any clinical pearls about integrating those in a way that's helpful for our patient?

对。

Yeah.

我觉得临床综合征和结构MRI或FDG-PET显示的神经解剖特征，这两者跟症状的关联最紧密，也最能帮助我们理解疾病的进展。

So I think the clinical syndrome and the neuroanatomy that you're gonna see from structural MRI or FDG PET, are those things are gonna be have the closest ties to linking symptoms and understanding disease spread.

而那些针对特定蛋白的生物标志物，才真正能帮我们判断是哪种蛋白沉积。

Those protein specific biomarkers are gonna be gonna be the ones that are gonna guide understanding the proteinopathy.

所以，其实可以把它看作三个不同的层面。

So really thinking about it as three different layers.

临床综合征和神经解剖特征，这两者之间的对应关系最紧密。

The clinical syndrome, the neuroanatomy, those two things are gonna have closer correspondence.

而神经病理学是另一个层面，我们确实需要特异性的蛋白标志物，目前阿尔茨海默病的已经比较成熟了。

And then this neuropathology is this other layer that we really need protein specific markers, and we've got good ones for Alzheimer's disease.

针对额颞叶变性的标志物也正在陆续出现。

They're starting to emerge for FTD.

我们现在有一些非特异性的标志物，比如NFL，同时也有初步研究在探索针对TDP-43和非阿尔茨海默型tau病变的PET标志物。

We have nonspecific markers like NFL, and then, there are rumblings and kind of phase one early studies of potential PET biomarkers for TDP 43 for four repeat tauopathies that occur in non AD tauopathies.

也就是FTLD型tau病变。

So FTLD tau.

我觉得这些标志物对个体层面判断究竟是哪种蛋白异常导致症状，会特别关键。

So I think those are going to be incredibly important for understanding at the individual level, which proteinopathy is causing this syndrome.

另外，对加速临床试验也很重要——药企对PPA试验兴趣不大，因为他们想测试的是能改变疾病进程的疗法。

Then also for really accelerating clinical trials, it's hard for the pharma companies to get excited about PPA trials because they want to of course trial disease modifying therapies.

而要这么做，就得把真正患有目标疾病的患者精准筛选出来。

And so in order to do that, need to get the right person with the right disease into that trial.

但因为临床表现和底层病理之间的关系太模糊，这一直是个难题。

And because of the ambiguity in the relationship between clinical phenotype and underlying pathology, that's been difficult.

其实也有过几个例外。

You know, there's been a few exceptions.

一个是最近针对语义性PPA的临床试验，因为语义型患者和TDP-43病理之间的关联实在太明确了。

One is the newer trial in semantic PPA because that link is so strong between the relationship is so strong between semantic having, the semantic variant and having TDP forty three as the pathology.

这算是个比较稳妥的选择，但要是将来能有PET扫描，或者更好的——血液生物标志物，那就更靠谱了。

It's a it's a safer bet, but it would certainly be strengthened by having those PET or, you know, hopefully blood based biomarkers in the future.

我至少看过一项研究，用人工智能和自然语言处理来区分PPA的不同亚型。

I've seen at least one study using artificial intelligence and natural language processing to classify PPA subtypes.

如果我们退一步看，刚才我们聊了这么多语言方面的问题，我觉得PPA这种痴呆综合征特别适合用AI来推进，毕竟它跟语言直接相关，而我们现在对大语言模型、自然语言处理这些技术都挺熟悉的。

If we step back, we've been obviously talking a lot about language, in this conversation and I think PPA is one particular dementia syndrome that may be especially ripe for advancement using AI given the language based techniques, large language models that many of us are very familiar with now, natural language processing.

目前很多AI研究都集中在词汇、语言和概念上。

A lot of the AI work has been around words and language and concepts.

所以我特别想听听你对目前这个领域进展的看法。

So I'm curious to hear you talk about where you feel like we're at with this currently.

是的。

Yeah.

我觉得这类工作其实有很多富有创意的用法。

I I think there there are a lot of creative uses for for work like that.

我觉得有必要退一步想想：你到底为什么要这么做？

And I think it's important maybe to step back and ask like, why are you doing it?

比如，是为了区分一个人只是偶尔词到嘴边说不上来，还是真的在患上某种进行性疾病？这可能特别有价值，对吧？

So is it to disambiguate someone who is worried well that they have that tip of the tongue phenomenon versus a progressive disease that might be particularly useful, right?

所以我们可以现在采集语音样本，三个月后再采一次，看看能不能发现语言能力有没有持续退化，能不能量化这种变化，从而更准确地诊断出是不是PPA，而不是其他原因导致的语言问题。

So that you say, let's get speech samples now and three months later and see if we can get at those, that there is there a progression that we can quantify to make a more accurate diagnosis to ensure someone has PPA relative to another cause to their, their changes in language symptoms.

这可能是其中一个特别有意思的应用方向。

So that might be one particularly interesting way to use it.

如果从认知神经科学的角度出发，想搞清楚大脑结构和语言之间的关系，理解语言网络到底是怎么组织的，那我觉得这确实是个能深入挖掘的好方法，能帮我们更透彻地理解语言的组织机制。

If the goal is to, from a more kind of cognitive neuroscience perspective, to understand the relationship between neuroanatomy and language, to understand how the architecture of the language network is organized, I think this is another way that we can really kind of deeply dig into those important and kind of nerdier, that understanding of the organization of language.

但如果只是为了把人简单分类成‘语法缺失型’或者‘词句迟缓型’，我就没那么兴奋了。

If the goal is to just be able to label someone as agrammatic versus logopenic, I get less excited about that.

但如果目标是真正弄清楚：这个人具体是哪些语言能力在衰退？因为这直接关系到我的语言康复计划和整体照护方案——那我就真的特别感兴趣，比一个笼统的标签重要多了。

If the goal is to say, I really wanna understand, does this person which aspects of language are really deteriorating because it's gonna guide my my speech language therapy plans, my care plan, I get more excited about that than a single label.

所以对我们来说，真正的挑战是和这个领域的量化专家紧密合作，共同确定哪些问题对临床最有价值。

And so I guess the challenge is really for us to work with our quantitative partners in this space to help guide the questions that will be most clinically useful.

我见过不少论文都用了机器学习，你知道的。

So I've seen, you know, with there's any number of papers that have used machine learning.

几年前我看过一个报告，有人用机器学习算法来区分语义性原发性进行性失语和健康人群。

So years ago, I saw a a presentation where someone did machine learning algorithm to to differentiate semantic PPA from healthy individuals.

那方法真是漂亮又精巧。

And it was, you know, beautifully elegant.

但其实我们也可以直接在那人面前放一支笔、一把剪刀和一个杯子。

We could we could have also put a pen, a pair of scissors, and a cup in front of that person.

要是你让他指出剪刀，他却指了杯子，那我们早就省下一大堆核磁共振检查了。

And if you ask them to point to the scissors and they pointed to the cup, we've now saved lots of MRI scans.

省了时间，也很快得到了一个明确的答案。

We've saved and we've and we've got a pretty definitive answer pretty quickly.

我这么说不是为了贬低，但我想强调的是：问题本身才最关键。

And so I don't do that to to belittle, but I I do say that the questions matter.

这些方法真的很精妙，能帮上大忙，但关键还是得靠多学科合作，让我们的数据专家真正深入进来，支持患者的照护。

And these are really elegant methods that really can help us, but it is this multidisciplinary partnership to help how can our quantitative colleagues really help us dig in to support care for folks.

这太好了。

That's great.

说到指导照护计划，我想现在聊聊具体的干预措施。

Talking about guiding care planning, I wanted to get into more interventions now.

我们刚才其实已经慢慢谈到这方面了。

We've been kind of inching there throughout the conversation.

我们之前提过像抗淀粉样蛋白这样的疾病修饰疗法。

We talked about disease modifying therapies like anti amyloid therapies.

那个就不多说了。

We don't need to rehash that.

我更想重点聊聊行为治疗。

I want to spend most of the time talking about behavioral treatments.

但在那之前，你对神经调控有什么看法？它对PPA患者有没有什么潜在好处？

But before we get there, is there anything you wanted to say about neuromodulation and how it might be beneficial for PPA?

比如经颅磁刺激或者经颅直流电刺激。

Things like transcranial magnetic stimulation or transcranial direct current stimulation.

在我们转向行为干预之前，你对这些有什么想说的吗？

Anything you wanna say about that before we move to behavioral interventions?

当然有。

Sure.

TMS和tDCS的思路是，它们通常和语言治疗或言语训练搭配使用。

So the idea of TMS or TDCS is that it's been paired with a speech therapy or language based intervention.

比如说命名训练，我们能不能通过加上TMS或tDCS来提升效果？

So maybe a naming intervention to say, can we boost, performance by adding TMS or TDCS?

目前已经有一些令人鼓舞的结果出来了。

And there's been some encouraging results that have come out.

我觉得下一步关键是要搞清楚这些效果能持续多久，还要确保实验设计够严谨、有对照组，这样才能看明白，如果要长期推广，到底该怎么操作。

And I think the key next steps are to understand what's the durability of those effects and to make sure we're using really elegant designs that are properly controlled so that we can understand what would this look like if we were trying to roll it out long term.

患者需要多久来一次？

How often would you need to come back?

所以关键是要分清楚，你问的到底是认知神经科学的问题——比如我们怎么干扰大脑回路、强化它，有没有可能；还是说从实际应用角度看，这种疗法长期有效吗？到底该怎么落地？

So really keeping an eye on implementation versus is the question a cognitive neuroscience question again about understanding how we disrupt brain circuits and strengthen that is it possible versus is it useful long term in an intervention and what would it look like from from an implementation standpoint?

我觉得这两个问题都很重要。

And I think both questions are important.

了解大脑的结构，尤其是语言相关的部分当然重要，但同样重要的是，我们要想清楚：在实验室里，控制得再完美，干预能短期见效，那到了真实世界里，还能不能推广开来？

It's important that we understand the organization of the brain and and particular language, but it's also important that we we think about not only can interventions show a change briefly in a laboratory set setting where everything is controlled perfectly, can that be extended to an implementation model?

所以从一开始就得说清楚：你这个问题，到底是关于语言在大脑中的组织机制、神经科学层面的探索，还是纯粹为了设计一种有效的干预手段？

And so again, being kind of clear about your question from the forefront, is it is the question around the organization of language and understanding the the cutting of neuroscience of language, or is it around being an intervention?

这两个方向其实都有人在做，而且目前出现的一些初步研究特别让人振奋。

And and I think there's there's work in both spaces, but exciting initial studies that have come out.

太好了。

Excellent.

那我们来聊聊针对原发性进行性失语症的一些行为干预方法，主要由言语语言治疗师来实施。

So let's get into some of these behavioral treatments for PPA delivered primarily by speech language therapists.

你之前说社工是天使，我完全同意，我觉得言语语言治疗师也该算在这一类里。

You mentioned earlier social workers as angels, I agree, and let's throw speech language therapists in that bucket as well.

他们为PPA患者做了特别棒的工作。

They do such great work for people with PPA.

要聊这个话题，我们可以从2024年的一项系统性综述说起。

One way to ground getting into this conversation is a 2024 systematic review on the topic.

Lisa Wouters和她的团队在《神经心理学评论》上发表了这项研究。

Lisa Wouters and colleagues published in the journal neuropsychology review.

他们分析了103项研究，覆盖600多名PPA患者，总体发现这些干预手段效果不错——主要指标有持续改善，训练外的技能也能迁移，而且疗效至少在一段时间内能保持住。

So they examined a 103 studies, over 600 patients with PPA and found good support for these interventions overall, including consistent improvement in primary outcome measures, good generalization to untrained targets which is important and at least some maintenance of treatment gains over time.

这一点对进行性疾病的患者尤其值得深思。

Also, something to really think about with a progressive condition.

针对找词困难的词汇提取训练，证据尤其充分。

Lexical retrieval treatments to improve word finding problems were especially well supported.

其他在PPA中显示出一定效果的方法还有脚本训练、旋律语调疗法，以及各种辅助或代偿性工具，帮助患者应对语言障碍。

Some other approaches that showed some benefits in PPA are script training, melodic intonation therapy and then there's various ancillary or compensatory devices to help people with language.

文献和临床实践中反复强调的一个关键点：治疗必须因人而异，量身定制。

Critical concept that comes up a lot in this literature and clinical care is just how important it is to individualize the treatment to the specific patient.

艾米莉，你刚才一直在谈这个。

You've been talking about this, Emily.

我们可不能搞一刀切的套娃式疗法。

We don't want a one size fits all cookie cutter approach.

得盯着眼前这个人来定制方案，等咱们聊到沟通桥梁疗法——你的工作——的时候，这点就特别关键了。

We need to think about the person in front of us and this will all be very relevant when we get into the communication bridge treatment, your work, very soon.

现阶段，关于这些行为疗法，你还有什么想说的吗？

For now, is there anything else you'd like to say about these behavioral treatments in general?

对。

Yeah.

我觉得咱们也得把这段历史的背景说清楚。

So I think there's it's it's important to kind of contextualize the the history here too.

十五年前刚起步的时候，关于PPA的语言治疗或者任何行为干预，研究少得可怜。

In the early studies, in really thinking kind of fifteen years ago, again, there was a very small number of studies that had been done in PPA speech therapy or really any behavioral intervention.

那时候大家最关心的问题是：在进行性综合征里，哪怕只是短暂地恢复几个词，可能吗？

And some of those early questions were in that space of, can you restore words at all in a progressive syndrome, even for a brief period of time?

所以那时候更多是在认知神经科学的层面问：这到底可能吗？

So it did fall a little bit more into that cognitive neuroscience realm of, is it possible?

而不是去想，这些词能不能永远保留下来。

And not necessarily thinking about, would they stay those words stay forever.

随着时间推移，早期的很多干预手段，包括系统综述里的那些，大多基于极小的样本或个案报告。

And over time, a lot of the early interventions and many of those that are in the systematic review are based on really small groups and case reports.

所以根本没有对照组。

And so there is no control group.

也没有随机分组。

They are not randomized.

这些研究在最初阶段其实特别关键，就是想搞清楚：这事儿到底行不行？

And this work was essentially was really essential in that kind of stage zero, stage one phase of understanding, is it possible?

有没有可行性？

Is it feasible?

能不能看到一点变化？

And can you see any sort of change?

但这些研究的质量还不够高，不足以证明它们真的有效或实用。

But it the quality of those studies was not at a level that is appropriate to show efficacy or to show effectiveness.

所以我觉得我们现在该转弯了，该转向真正验证效果和实用性的试验了。这在很多疾病和综合征里都一样——实验室里有效的干预，往往就是没法落地。

And so I think where we're at now is we really wanna turn that corner and move into efficacy, effectiveness trials and thinking about it's true for so many different diseases and syndromes that there are interventions that can be efficacious in the lab, but they still never make it to implementation.

所以，实现落地的工作得从一开始就考虑，开发干预方案的时候就得问：这东西将来真能用得上吗？

And so the work of getting to implementation has to start early and thinking about as I'm developing this intervention, would it ever be implementable?

它真的有实现的可能吗？

Is it ever possible?

如果你从这个问题出发，反而能帮你更好地规划未来，也更清楚每个阶段该问什么问题。

And if you start with that base, I think it helps you build for the future, and to to really clarify what questions are you asking at each time.

所以这个综述让人兴奋，因为它显示这些年来干预手段的数量明显增加了，而且即使在没有对照组的情况下，也确实观察到了一些进步，而且能维持一段时间。

So the review is exciting because it shows that there's been a real increase in, the number of interventions over the years and that they are reliably seeing, albeit in non controlled settings, some gains, and then maintenance for for various periods.

有时候能维持一个月。

Sometimes it's a month.

有时候能维持两三个月。

Sometimes it's a couple months.

但很多这类研究都集中在两大类上：一种是针对功能缺陷的干预，另一种是恢复性的干预，而系统性综述里的大部分研究都属于这两类。

But many of those studies focused, if we if we split into two broad categories, there can be impairment based or restorative based interventions, and that's where the majority of these fell, in that systematic review.

它的思路是，试图恢复或重建已经丧失的语言能力，通过重复训练或高强度的治疗活动，直接作用于背后的认知机制。

And the idea there is that you're trying to restore or bring back language that has been lost, And you're trying to do that because you're targeting the underlying cognitive processes through repetition or intensive therapeutic activities.

还有一派则更关注：语言障碍到底怎么影响了你的日常生活？我们该怎么设计辅助策略来应对？

Then there is the other camp, which is really thinking about how is the disruption in language impacting your daily life and how do we think about compensatory strategies?

不只是修复，更要思考：哪些辅助方法能真正帮你在日常中应对自如？

So not just restoring, but how do we think about, the compensatory strategies that may help you day to day?

几年前，学界就隐隐有个说法，认为在PPA（原发性进行性失语）中，这两种方法应该按顺序来。

And there was sort of a rumbling several years ago that these should go in order in PPA.

意思是，早期轻度阶段只用缺陷修复法，等这些方法失效了，再引入辅助策略或个性化方案。

That when you're in the mild phases, you should use impairment based only, and you should only bring in compensatory strategies or these personalized strategies after the impairment based strategies are no longer working.

但我读了这些文献后觉得，其实我们早该同时用上两种方法——如果等太晚才开始教辅助策略，可能就错过建立隐性记忆、固化日常习惯的最佳时机了。

When I started to read this literature, I was like, well, I seems like we wanna bring in both early because if you wait too long to start putting in some of these compensatory strategies, there may be less opportunity to lay down the the implicit memory to get those routines down.

比如，趁早教患者用沟通笔记本，这样一旦说话时想不起某个词，就能立刻翻出来，有个备用方案。

So for example, teaching someone how to use a communication notebook early on so that if you can't remember a word in conversation, you have a backup plan and you can bring out that notebook.

对现在语言能力还不错的患者来说，这听起来可能有点尴尬。

And that might sound embarrassing to someone who still has pretty good, grasp on their language right now.

但早点教会他们用这个备用方案，等以后语言能力下降了，反而会让他们更有掌控感。

But having that backup plan, and teaching them how to use that early on becomes then empowering when that language is less accessible later on.

所以我们考虑的方式是：第一，尽可能最大限度地保留他们的语言能力。

So some of the ways that we have thought about it is really thinking about one, let's maximize your language ability as much as we can.

第二，同时也要提前准备好替代策略，因为日常生活不该是考你能不能马上想起某个词的测试。

But two, let's also build in compensatory strategies because your everyday life shouldn't be a test that you can only, you can't move on if you can't access the word.

你得有个备选方案。

You should have a backup plan.

我觉得这很有道理。

Makes sense to me as well.

如果你能简单介绍一下几种语言治疗手段，比如词汇提取训练、脚本训练、旋律语调疗法，可能会很有帮助。

It might be helpful to hear you describe a few of the speech language interventions, what they look like, such as the lexical retrieval treatment, script training, melodic intonation therapy.

有些名字一听就大概知道是干嘛的，不用讲太细，你就挑几个SLP最常用的疗法，简单说说就行。

Some of them are self explanatory based on the names, and we don't have to go into all the details, you wanna just give a little bit of an overview of some of the most common treatments that SLPs use?

比如词汇提取策略，就是背一串词，反复练习，有时候用一种叫SFA的方法，也就是语义特征分析——把一个词拆成几个部分来分析。

You know, kind of lexical retrieving strategies, they can be learning a list of words and practicing them over and over again, sometimes through something called SFA, which is semantic fixture analysis, so that you take a word and then you break it down into components.

它有什么用？

What is its function?

它是怎么运作的？

How does it do this?

这样能激活相关的语义网络，帮你更容易想起那个词。

And so that you're activating the semantic network that will hopefully help you access that actual word.

这方面其实有很多练习方法。

So there's ways to practice these in that realm.

脚本训练呢，就是设计一些不同难度的对话脚本，从简单的开始，慢慢升级，核心是让你对这些表达越来越自动化，说话更流畅。

The idea around script training is also setting up these scripts in a certain level of difficulty that you can start at an easier level and then get more difficult, but you're really trying to increase the automaticity with which that language comes to you so that it helps your fluency.

关键是反复练，你可以先听别人示范，然后跟着复述。

And so the idea is that by practicing these scripts over and over and they can be modeled for you and then you can repeat them back.

也可以一边看一边跟读。

You can read along with them.

所以我们可以系统地逐步去掉那些提示，或者学会记住它们，通过反复背诵来重新获得那种自动性和流利度。

And so there's different ways of kind of taking, the different cues away in a systematic way and or remembering them, you know, learning to recite them to get that automaticity, that fluency back.

而且这种效果也能迁移到日常生活中。

And the idea is that would generalize also to your everyday life.

太好了。

Great.

你们的沟通桥梁项目有几个关键特点：根据每位患者的具体情况定制治疗方案、使用远程医疗、让照护者直接参与治疗，还提供一个定制的网页应用。

And a few key features of your communication bridge program include individualizing the treatment to the specific patient, utilizing telehealth, directly involving the care partner in treatment, offering a custom web based app.

我还了解到，你们在这项疗法中特别关注现实生活中的日常功能改善，这并不意外，毕竟你刚才的每一句话都切中要害。

It's also my understanding that you've focused on real world everyday functioning outcomes with this therapy, which is not surprising given your comments throughout this discussion, which I think are apt.

能跟我们说说你们的具体方法、用到的技术，以及目前有哪些研究证据支持吗？

Tell us about the approach, some of the specific techniques used, and the evidence supporting it to date.

我得再次感谢那些家中有确诊患者的人，正是因为他们，这个临床试验才得以启动。

So I really have to thank again individuals living with a diagnosis in their families because that's how this trial came to be.

作为一名神经科学家，我原本根本没打算做临床试验。

As a neuroscientist, I had no intention of being a clinical trialist.

其实我当时把那些课全跳了，心想：我才不当药企研发呢。

In fact, I kind of skipped all of those classes when I was, I was like, I'm not going to be a drug developer.

我根本没必要懂这些

I don't need to know how to go

去，我

to, I

也不用学怎么搞临床试验。

don't need to know how to run clinical trials.

但后来我们做了一项针对原发性进行性失语症患者的研究。

But, I was, we were running this observational study for individuals with primary progressive aphasia.

因为这种病太罕见了，我们的研究对象覆盖了整个美国和加拿大。

Because it's so uncommon, our catchment zone for this trial was or for this observational study was The United States and Canada.

所以我们联系家属，全额承担他们的机票、酒店和所有差旅费用，只为了让他们来参与研究。

And so we would connect with families and we would pay for their, flights and hotel and accommodations all over their travel to come and participate in the study.

研究完他们就回家，之后再定期回来做长期跟踪。

And then they would go home and then they would come back longitudinally.

那段经历里，十五年前，有些家庭会打电话回来告诉我们：‘罗加尔斯基，我们参加研究的那段时间特别开心，第一次了解到这么多关于原发性进行性失语症的信息。’

And in that experience, fifteen years ago, had families that would call back and say, Rogalski, we really enjoyed our time when we came for the study and we learned a lot about PPA that we had never heard before.

但现在我们回到家，却找不到任何一个医生听得懂你在说什么。

But now we're home and we can't find a clinician who knows what you're talking about.

我们的神经科医生说，我们什么都做不了，言语治疗师也帮不上忙。

Our neurologist says that there's nothing that we can do and speech therapists don't, can't help us either.

他们只会说，这病会慢慢恶化。

They just say it's progressive.

这话简直像一刀捅进心里。

And that was just like a dagger.

我当时就想，一定有什么办法能帮到他们。

I said, there's got to be something that we can do.

但我们受限于地域——就算在芝加哥这样的大城市，也找不到足够多确诊患者来开展一项临床试验。

But we were really constrained geographically because to run a trial, even in the large city of Chicago, there wouldn't be enough individuals with a diagnosis to run a trial.

从行为干预的角度来看，让患者专程搬来芝加哥住六个月，住完再回去，过段时间又回来，这根本说不通。

And it doesn't make logical sense from a behavioral intervention to ask people to come live in Chicago for six months and then come home and then come back.

所以我们得找别的办法，这事儿大概十五年前吧。

So we needed a different solution and this was again, you know, fifteen ish years ago.

那时候还没疫情，Zoom也没普及，大家已经开始用Skype和FaceTime了。

And so at that time, this was before the pandemic, before zoom, people were starting to use in their everyday life, Skype and FaceTime.

Skype特别棒，因为你能直接打给国外的人，还不用付长途话费——以前这可是个大问题。

Skype was particularly exciting because you could now call people, in other countries and you didn't have to pay for long distance charges because that used to be a thing.

我就想，既然大家，不管是老人还是年轻人，都习惯用这些科技工具，那能不能用它把确诊家庭和专业的语言治疗师连起来？

I said, can we take advantage of this fact that people are comfortable using technology, older adults, younger adults, and utilize it as a way to connect an individual with a diagnosis in their family to an expert speech language therapist.

这些年来，我很幸运遇到了一群特别有热情的语言治疗师，和他们一起把这套干预方案慢慢做起来了。

And so just have had the great fortune over the years of meeting really passionate, speech therapists that I've worked with to then build out the intervention.

我们不只想做一小时的咨询，更希望患者能在一小时之外，有办法巩固和延续治疗效果。

And we wanted it to be more than just an hour long session, but for them to have the opportunity to have, ways to reinforce that intervention outside of their hour long session.

我常拿物理治疗打比方：你扭了脚踝，做康复训练，坐在治疗师面前觉得动作很简单，可他们给你一张当年那种模糊的复印纸，教你回家怎么练。

So I sometimes use again a physical therapy analogy that if you go in and you hurt your ankle and you have ankle exercises, they seem very easy, when you're sitting with your physical therapist and then they hand you, at least back in the day, a bad Xerox copy of how to, do those exercises at home.

可一回家，天哪，根本记不清动作要领了，瞬间觉得哪哪都不对。

Once you're home, man, they don't seem so easy because you can't remember exactly how you're supposed to do them.

所以我们开发了一个专属的网页应用，来支持这个干预方案，里面包含了家庭练习和对话脚本。

So we developed a custom web application to support the intervention that would have home exercises so that they could practice, scripts.

他们可以练习词汇提取。

They could practice lexical retrieval.

这样一来，治疗的剂量就不只是那一个小时的专家面谈了，他们还能在家用这个工具，视频也会反复强化他们学到的技巧。

And so the only dose of intervention didn't just come in that hour with their expert clinician, but they had the opportunity to utilize this at home, and that there would be videos that reinforce the strategies that they learned.

这些视频可以慢放、快进，想看多少遍都行，如果愿意，还能分享给家人。

They could watch those as slowly or fast or, you know, as many a times and share them with family if they chose.

一开始我们也不知道这能不能行得通。

So, we started, we didn't know if it would be feasible.

所以第一步，我们只想看看有没有人愿意参与，看看远程治疗到底靠不靠谱。

So first we just had to see if people would show up and if this would be possible over telehealth.

那时候，保险和执照问题一大堆，障碍重重。

There were many, many barriers from an insurance standpoint and from a licensure standpoint at the time.

我常讲，新冠倒是带来了一个意外的好处——彻底改变了我们对远程治疗的监管政策，尤其是言语治疗这块。

And I often say it's I think the one thing that went well with COVID is how we changed our telehealth, regulations, particularly for speech therapy.

在最初的研究中，我们成功招募了来自全球的57名参与者，包括西班牙、新加坡、美国和加拿大，证明了这个方案是可行的，而且确实带来了一些初步的改善。

And so in that initial study, we were able to enroll 57 individuals from across, the globe in Spain, Singapore, and The US and Canada, and showed that it was feasible, possible, and some kind of initial, gains.

这让我们得以启动这项随机对照试验，思考：如果干预方式是双人协作的，聚焦于患者实际面临的困难，会不会比只针对语言障碍的干预更有效？

That allowed us to start this randomized control trial, thinking about would an intervention that is dyadic in nature and focuses on the challenges that the individuals was experiencing would be more robust than an impairment only intervention.

这个项目现在还能用吗？其他治疗师也能用吗？

Is this still available or is it available to other clinicians?

博士。

Dr.

是的，这是个很好的问题。

Yeah, so great question.

我想接着聊聊之前提到的关于疗效和落地实施的一些看法。

To touch on some of the comments I was making earlier around efficacy and implementation.

疗效确实不错，这一步很重要。

Efficacy is great, and that's an important step.

我们在Communication Bridge二期试验中已经证明了疗效，但还有很多问题没解决。

And we were able to show efficacy with our Communication Bridge two trial, but there are many questions that still remained.

所以我们现在有一个正在进行的试验，正在进一步优化，离实际应用更近了一步。

And so the we now have an active trial that is further refining and moving us closer to implementation.

我们提出了一些不太一样的问题，来打磨这个干预方案，弄清楚哪些部分最关键、哪些要素最有效，好让这个方案不只是靠那些全球顶尖的言语治疗师才能实施，而是能让那些从来没接触过原发性进行性失语症患者的治疗师也能快速上手，掌握必要的知识去照顾这类病人。

So asking quite, slightly different questions to refine the intervention and to understand which components are are most important, which ingredients are important, and moving us closer to implementation so that it's not just special speech therapists with all the expertise in the world that can deliver this intervention, but how do we make it so that other speech therapists who may not have had the opportunity to treat someone with PPA before, how do you get them ramped up and to, with the knowledge to care for someone with primary progressive aphasia?

对大多数言语治疗师来说，他们整个培训里可能只有一小时是讲所有类型痴呆的。

And this is probably a good point to highlight that for most speech therapists, they may have only a single hour that covers all dementia syndromes.

所以他们没准备好，或者感到不自在，其实一点都不奇怪——他们的课程里有时根本没涉及神经退行性疾病。

So it's not surprising that they're not equipped to, or they may feel uncomfortable because their didactic portion of their programs sometimes doesn't cover neurodegenerative disease at all.

就算有，也往往只是蜻蜓点水。

And sometimes is just very, very small points.

你想啊，要把帕金森、阿尔茨海默、原发性进行性失语和额颞叶痴呆全塞进一小时里讲，那简直荒唐。

If you think about trying to cover Parkinson's and AD and PPA and FTD in a single hour, it would be kind of, it would be ludicrous.

所以我们开始思考实施模型，琢磨怎么设计一个‘中心-辐射’式的推广模式。

So, we've thought about implementation model and starting to think about how would that kind of hub and spoke model might look for implementation.

在这项研究里，我们还加入了成本分析，好更清楚实际落地需要多少资源，同时也在不断精简试验中的某些环节，让临床医生在真实环境中操作时，能自然地用上这套方法，而不是像传统随机对照试验那样脱离现实。

And so in this study, we include cost analyses so that we can better understand what it would look like to implement, and then just really refining and removing some of the, components of a trial and putting if a clinician would be doing it and the research in the clinical setting, then they would be doing it in this trial as opposed to an RCT.

有时候会有协调员负责某些工作，以维持干预的有效性。

Sometimes you have coordinators who are doing certain aspects to keep at efficacy stage.

我们对这个新试验非常期待，目前正在积极招募参与者，欢迎任何转介。

We're excited about this new trial and are actively enrolling participants, so would appreciate any referrals.

太好了。

Awesome.

你有什么建议，能帮我们找到有PPA经验的语言治疗师吗？还有，怎么才能最有效地和这些治疗师以及跨学科团队其他成员合作？

Do you have any tips for how to find speech language therapists who have experience with PPA, and then the most effective ways of interfacing with those therapists and other members of interdisciplinary teams?

是的。

Yeah.

我觉得前额叶变性协会在这方面是个很好的资源，能帮助患者和家属找到照护和支持服务。

So I think the Association for Frontotemporal Degeneration has been a really good resource for trying to connect individuals with care and support.

他们的网站上经常会列出一些有支持小组的机构，这对家庭来说也是非常重要的支持方式。

And so sometime they, on their website, they'll list places that have support groups, which is another really important ways to support families.

他们还会列出正在进行的临床试验和其他研究项目。

They also list active clinical trials and other studies.

要找一套完整的、有经验的言语治疗师名单真的很难。

It is difficult to get a full listing of of therapists who have experience and approach.

所以我觉得这正是我们需要重点关注和填补的一个空白。

And and so I think that's an a gap in an area of growth that we we should think about addressing.

艾米莉，再次衷心感谢你。

Well, Emily, once again, thank you so much.

这简直是一堂关于PPA的精品课。

This has been a master class in PPA.

我们太幸运了，能有你这样的专家。

We are very fortunate to have you.

约翰和我早就一直在讨论这种综合征，或者说这一组神经病理状况。

John and I have been talking about this syndrome slash group of neuropathological conditions for a while.

我们一直想搞定神经心理学家会遇到的所有原发性退行性疾病。

We've been trying to tackle, you know, all of the primary degenerative diseases that neuropsychologists can see.

我们已经覆盖了挺多，但PPA一直还没碰上。

We we've hit on a bunch of them, but not PPA yet.

真的太感谢你了。

So thank you so much.

我只是很感激能有这个机会。

Well, I just appreciate the opportunity.

我一直是那些确诊患者及其家人的坚定支持者，真的很感谢能有这次机会。

I'm a staunch advocate for individuals, living with a diagnosis and their families, and just appreciate the opportunity.

好了，今天这一期就到这里。

Well, that's it for today's episode.

如果你想支持我们，这里有几种简单的方式。

If you'd like to support us, here are a few easy ways.

第一，你可以为精选的 NavNeuro 节目获取 APA 认证的继续教育学分。

First, get APA approved CE credits for select NavNeuro episodes.

去 navneuro.com/ins 就行。

Go to navneuro.com/ins.

第二，去看看我们的书《成为神经心理学家》，并在亚马逊上给个评价。

Second, check out our book called Becoming a neuropsychologist and leave it an Amazon rating.

第三，别忘了跟朋友和同事推荐一下NavNeuro。

And third, you can tell your friends and colleagues about NavNeuro.

一如既往，非常感谢你的收听，下次我们继续探索大脑与行为的奥秘。

As always, thanks so much for listening, and join us next time as we continue to navigate the brain and behavior.

《探索神经心理学》播客及其所有相关内容仅供一般教育参考，不构成任何心理学或其他专业医疗服务的建议。

The navigating neuropsychology podcast and all the linked content is intended for general education purposes only, and does not constitute the practice of psychology or any other professional healthcare advice and services.

我们，约翰·贝洛安和瑞安·范帕滕，与本播客的听众之间不构成任何专业服务关系。

No professional relationship is formed between us, John Beloan and Ryan Van Patten, and the listeners of this podcast.

《探索神经心理学》及其相关材料的使用风险由听众自行承担，大家务必向合格的持证医疗或心理专业人员寻求适当的诊疗服务。

The information provided in navigating neuropsychology and the materials linked to the podcast are used at listeners own risk users should always seek appropriate medical and psychological care from the appropriate licensed health care provider.