比尔·盖茨：总有一天我们会用意想不到的方法诊断阿尔茨海默病

2019 年 4 月 10 日 全球创新论坛

“在美国，阿尔茨海默症是十大死亡原因之一，却是其中唯一没有有效治疗手段的死因，每年的发病率都在增加。‘推迟阿尔茨海默症的发病时间和减少它对认知能力的影响’是一个可以大幅提高人类生存质量的前沿领域。我很激动能加入对抗这一疾病的战斗，并看到一些希望。”

作者：Bill Gates

来源：比尔盖茨（ID：gatesnotes）

如果不能用一种简单的方法来诊断阿尔茨海默症，我们该如何消灭它？

就像我去年写的那样，这真的是一个鸡和蛋的问题。找到阿尔茨海默症的治疗方法需要大量新药的临床实验，但是如果不能在发病初期发现这些患者，从而测试治疗方法是否能发挥作用，那么就很难招募到合适的实验参与者。

目前，诊断这种疾病的最佳方法是脊椎穿刺或脑部扫描。问题在于前者具有侵入性，而后者价格昂贵。另外，许多病人在开始出现认知能力下降的迹象之后才进行这些测试，而此时病情可能已经相当严重了。找到一个可靠、价格可负担和好用的诊断方法对于消灭阿尔茨海默症的重要性，再怎么强调都不为过。

好消息是，多亏过去几年里取得的重大突破，这个目标终于变得触手可及。

科学家们正在推进新的诊断方法：从简单的血液测试到语音分析，这些方法就好像科幻小说里写的一样。我们已经接近攻克鸡和蛋问题的临界点了。

这就是我投资诊断法加速器（Diagnostics Accelerator）的原因——我去年夏天宣布与阿尔茨海默症药物发现基金会（ADDF）一起投资了这个新的基金，旨在加快现有的研究进展。

我很感激我的朋友杰夫·贝佐斯和麦肯齐·贝佐斯，他们一直是全心全意致力于消除这一疾病的好伙伴。在接下来的几个月里，我们将继续一起寻找诊断阿尔茨海默症的新方法和进行其他方面的努力。

与此同时，该基金正准备宣布第一轮的获奖项目。

就在不久前，我们还没有除了认知评估之外的阿尔茨海默症诊断方法。第一次突破出现在20世纪90年代末和21世纪初，那时大脑成像——如PET（正电子发射断层扫描技术）和MRI（磁共振造影）——使我们能够看到患者大脑的生物学变化。

随后在2006年出现了脊椎穿刺。一个由瑞典科学家奥斯卡·汉森（Oskar Hansson）、亨里克·塞特伯格（Henrik Zetterberg）和卡伊·布兰纳（Kaj Blennow）组成的团队，证明了观察脑脊髓液（在大脑和脊髓中发现的液体）可以预测哪些人会患上阿尔茨海默症。他们的发现为研究人员提供了一个可使用的工具，利用这个工具，他们能够更明智地决定应该找哪些人参加临床实验。

不过这个办法并不完美，问问那些做过脊椎穿刺的人是否愿意再经历一次这个过程就知道了。

理想的阿尔茨海默症诊断方法是什么样的？它得是便宜和易于操作的。它不仅能告诉我们是否患上了阿尔茨海默症，还能告诉患者病情的严重程度。（胆固醇测试并不仅仅只是告诉你是否有胆固醇，它能指出你的胆固醇水平以及这个水平是否会影响健康。）最重要的是，理想的诊断方法应该像你在年度体检中接受的其他常规检查一样简单且无痛。

换句话说，血液检测会是一种理想的诊断方法。

就在两年前，科学家们对于是否存在简单的阿尔茨海默症血液检测还存有疑虑。研究人员们已经寻找了很长一段时间，但每次新的实验室检测显示出一些希望，下一个尝试它的科学家却会实验出与之相异的结果。

兰迪·贝特曼（Randy Bateman）是圣路易斯华盛顿大学的教授和研究员。作为最早的发现者之一，他的团队识别出阿尔茨海默症患者的血液在众多测试中存在具有一致性的变化。自从2017年夏天他公布研究以来，其他研究人员也发表了类似的发现，还有很多人在努力完善这个诊断方法（包括发明脊椎穿刺检测的瑞典团队）。

在接下来的一两年内，血液检测很有可能被用于招募患者进行阿尔茨海默症的药物试验。

这令人非常兴奋，因为这意味着实验室将能更快地招募到更多病人，同时科学家将能在更短的时间内弄清楚某种药物是否有效。这也意味着将来有一天，你能很容易地在医生的例行检查中进行这种检测。

但如果我们能够找到一种侵入性更小的方法来诊断阿尔茨海默症呢？如果我们可以使用数字技术而不是医学，在人们智力开始下降的前几年就诊断出疾病呢？

我最近遇到了一位名叫罗达·奥（Rhoda Au）的研究人员，她正在研究一些检测阿尔茨海默症的很酷的方法。如果她的研究被证明是成功的，也许有一天，我们可以简单地通过听声音或者观察如何用笔写字来预测你是否会得这种病。

奥博士负责弗雷明汉心脏研究中的神经心理学研究，该研究已经持续七十多年追踪一个城镇中居民的健康状况了。由于这项研究已经进行了很长时间，一些参与者最近已经患上了阿尔茨海默症——并且奥博士有这些病人这段时间参与健康评估的数千份音频文件的使用权限。

当你说话的时候，有很多事情在发生。把词串在一起组成句子的整个编译过程很复杂。

如果能用电脑分析一个阿尔茨海默症患者多年来是如何说话的，你也许能发现一些细微的变化，然后在还未显现阿尔兹海默症症状的更年轻的病人身上寻找相同的言语模式。如果你能足够早地发现这些变化，你甚至也许能从一开始就防止人们患上阿尔茨海默症（但为了做到这一点，我们也需要在预防阿尔茨海默症方面取得进展）。

我们还不知道语音分析是否有效，这还处于研究的早期阶段，我们甚至还不知道应寻找什么样的言语模式变化。（奥博士也在研究其他的数据化指标，比如利用在长时间使用数码笔的过程中书写习惯是否会变化来进行识别。)

但我对未来充满期待，到那个时候，判断人们阿尔茨海默症患病风险的大小有可能就像使用手机应用一样简单，你可以让应用提醒你讲话中出现的危险信号。

从今天起，诊断法加速器已经开始接受第二轮资助申请，他们尤其在寻找依靠数字工具检测阿尔茨海默症的想法。如果你有好的想法，可以点击“阅读原文”申请资助。

对于诊断方式来说，如今是一个充满奇迹的时代。

随着技术越来越先进和精确，科学家们在诊断疾病方面正在取得惊人的进展。对阿尔茨海默症的研究已经受益于这种更深入的了解，我也期待在未来看到其他革命式诊断方法的出现。

附：英文原文

The unexpected way we might one day diagnose Alzheimer’s

How do you stop Alzheimer’s disease without a simple way to diagnose it? It’s a real chicken and egg problem, as I wrote last year on TGN. Discovering a treatment for Alzheimer’s requires lots of clinical trials for new drugs—but it’s difficult to enroll participants without a way to identify people who have the disease early enough for potential treatments to work.

Right now, the best way to diagnose the disease is through a spinal tap or a brain scan. The problem is that the former is invasive and the latter is expensive. Plus, many patients don’t get these tests until they start showing signs of cognitive decline, which means the disease may already be pretty advanced. It’s hard to overstate how important finding a reliable, affordable, and easy-to-use diagnostic is for stopping Alzheimer’s.

The good news is that we’re finally within reach of that goal thanks to significant breakthroughs over the last couple years. Scientists are pushing forward with new diagnostics that range from simple blood tests to voice analysis straight out of a sci-fi novel. We’re close to reaching the point where we can push past the chicken and egg problem.

That’s why I announced last summer that I was investing in a new fund with the Alzheimer’s Drug Discovery Foundation called Diagnostics Accelerator, which aims to accelerate the progress already underway. I am grateful to be joined in this effort by my friends Jeff and MacKenzie Bezos. They have been tremendous partners who are deeply committed to finding an end to this disease. We’ll continue to work together on finding a new way to diagnose Alzheimer’s, as well as on other efforts, over the coming months. In the meantime, the fund is getting ready to announce the first round of awards.

It wasn’t that long ago that we had no way to test for Alzheimer’s beyond cognitive assessments. The first breakthrough came in the late 1990s and early 2000s, when brain imaging (like a PET scan or MRI) allowed us to see biological changes in the brain of someone with the disease.

Then came the spinal tap in 2006. A team of Swedish scientists—Oskar Hansson, Henrik Zetterberg, and Kaj Blennow—demonstrated that you could predict which patients would develop Alzheimer’s disease by looking at cerebrospinal fluid (the fluid found in the brain and spinal cord). Their discovery gave researchers a more accessible tool to make smarter decisions about who should be in a clinical trial. It wasn’t perfect, though—just ask anyone who’s ever had a spinal tap whether they’re eager to undergo the procedure again.

What does the ideal Alzheimer’s diagnostic look like? It needs to be cheap and easy to administer. It should tell us not only whether you have Alzheimer’s, but how far advanced the disease is. (Your cholesterol test doesn’t just tell you that you have cholesterol, after all—it lets you know how much you have and whether it could be a problem.) Above all, it should be as simple and painless as any of the other routine tests you get during your annual physical.

In other words, a blood test would fit the bill.

As recently as two years ago, scientists were skeptical we would ever have a simple blood test for Alzheimer’s. Researchers have been on the hunt for one for a long time, but every time a new lab test showed some promise, the next scientist who tried it couldn’t get the same results.

Enter Randy Bateman, a professor and researcher at Washington University in St. Louis. His team was one of the first to identify changes in the blood of Alzheimer’s patients that remained consistent over many tests. Since he published his research in the summer of 2017, other researchers have released similar findings, and a lot of people are working to perfect the diagnostic (including the Swedish team that discovered the spinal tap test).

There’s a good chance a blood test will start being used to recruit patients into Alzheimer’s drug trials within the next year or two. That’s super exciting, because it means that labs will be able to recruit more patients more quickly, and scientists will be able to figure out whether a drug works in less time. It also means that you’ll one day be able to easily get tested during a routine doctor’s visit.

But what if we could find an even less invasive way to diagnose Alzheimer’s? What if we could use digital technology, not medicine, to identify individuals years before they start to develop mental decline?

I recently met a researcher named Rhoda Au who is working on some seriously cool ways to detect Alzheimer’s. If her research proves successful, we might one day predict whether you will get the disease by simply listening to the sound of your voice or watching how you write with a pen.

Dr. Au is in charge of neuropsychology for the Framingham Heart Study, which has tracked the health of one town’s residents for more than 70 years. Because the study has been going on for so long, some of the participants have developed Alzheimer’s recently—and Dr. Au has access to thousands of audio files of those patients participating in health assessments over the years.

There’s a lot going on when you speak. The whole assembly process of how you string words together and form sentences is complicated. If you could use a computer to analyze how an Alzheimer’s patient speaks over the years, you might be able to pick up on subtle changes—and then look for those same patterns in younger patients who show no other signs of the disease. If you’re able to identify those changes early enough, you might even be able to stop someone from getting Alzheimer’s in the first place (although we’d also need advances in Alzheimer’s prevention to do that).

We don’t know yet if voice analysis will work. It’s still early in the research process, and we don’t even know what changes in speech patterns we’re looking for yet. (Dr. Au is also investigating other digital markers, like whether you could identify changes in writing habits over time using a digital pen.)

But I’m excited about a potential future where identifying your risk of developing Alzheimer’s is as simple as an app on your phone that you can instruct to listen for warning signs in your speech. Starting today, Diagnostics Accelerator is accepting applications for the second round of funding, and they’re specifically looking for ideas that rely on digital tools to detect Alzheimer’s. If you’ve got a great idea, you can apply for funding here.

This is a miraculous age for diagnostics. As technology gets more advanced and more precise, scientists are making amazing progress in how we pinpoint disease. That deeper understanding is already benefitting Alzheimer’s research, and I’m eager to see what other game-changing diagnostics it unlocks in the years to come.