比尔·盖茨：我为什么要钻研阿尔茨海默症

在世界的每个地方，人们都比过去更长寿。多亏了科学的进步，更少人会因为心脏病、癌症和传染病而英年早逝。一个人到80多岁还能活得很好已不再是稀罕事。我父亲就将在几周后迎来他92岁的生日，活到这个岁数在他出生的那个年代几乎是无法想象的。

 

人类的寿命比以前更长，这应该是一件开心事才对。但如果长寿不能使人开心，那会发生什么？

你活的时间越长，就越可能出现慢性病的情况。你罹患关节炎、帕金森病或其它降低你生活质量的非传染性疾病的风险逐年递增。不过在所有威胁到我们晚年生活的疾病中，有一种对社会的危害尤为严重，那就是阿尔茨海默症。

 

你如果活到80多岁，就会有接近50%的可能性得这种病。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。随着美国在“婴儿潮”时期出生的一代人步入老年，这种趋势将会继续扩大。这意味着有更多的家庭将眼睁睁地看着他们亲人的认知能力减退，然后慢慢地消失。尽管疾病负担越来越重，科学家们还是没能弄清到底是什么原因导致了阿尔茨海默症，以及如何才能阻止这种疾病破坏大脑。

 

我最初对阿尔茨海默症产生兴趣是由于它对家庭和医疗系统造成的负担——既是情感上的负担，又是经济上的负担。这种病的经济负担更容易量化。比起没有神经退行性疾病的老年人，患阿尔茨海默症或其他形式痴呆症的病人，每年在自费医疗项目上要多花五倍的钱。与许多患慢性病的人不同，阿尔茨海默症患者既要支付长期护理的费用，又要负担直接的医疗开支。如果你在六七十岁得了这种病，你在接下来几十年里可能需要昂贵的护理。

 

这些开支是发达国家增长最快的医疗负担之一。根据阿尔茨海默症协会提供的数据，美国人在2017年将花费2590亿美元看护那些患阿尔茨海默症及其它痴呆症的病人。如果没有重大突破，在未来几年甚至几十年里，这些支出还将继续挤压财政预算。这些问题是世界各国政府都需要考虑的，包括那些中低收入国家——那里的国民预期寿命也在接近全球平均水平，患痴呆症的人数正不断增加。

想要把阿尔茨海默症造成的人力成本转化为数字，这实在是难上加难。这是一种可怕的疾病，它摧毁的不仅是得病的人，而且包括所有爱他们的人。我对此深有感触，因为我的家族中就有人得过阿尔茨海默症。眼睁睁地看着你爱的人挣扎着被这种病夺走心智而你却对此无能为力，我知道那有多么的痛苦。这感觉很像是在经历你曾经认识的那个人一点点死去的过程。

 

我的家庭背景并不是我对阿尔茨海默症产生兴趣的唯一原因。但我的个人经历确实让我明白，当你或你爱的人患上这种疾病时，那种感觉有多绝望。我们已经看到科学创新的力量，它将像艾滋病毒这样曾经不可一世的杀手，转变成为可以通过服药被控制住的慢性疾病。我相信我们对阿尔茨海默症也能做到这一点（或者做得更好）。

 

过去一年，我花了大量时间研究这种疾病和迄今为止取得的进展。在这个领域里，人们正在开展许多了不起的工作，目的是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。我从研究人员、学者、投资人和业内专家等各方听到的信息使我信心满满，只要我们可以在五个领域取得进展，我们基本上就能改变阿尔茨海默症的发展方向。

 

• 我们需要更深入地了解阿尔茨海默症是如何发生的。大脑是一个复杂的器官，由于病人在世的时候很难对大脑进行研究，我们对它如何随着年龄老化，以及阿尔茨海默症如何破坏了这个过程知之甚少。我们对大脑状况的认识大部分来自于尸体解剖，所以只能看到阿尔茨海默症末期的表现，而无法解开其长久以来的谜团。例如，我们无法完全理解为什么非洲裔美国人或拉丁美洲人要比白人更容易患阿尔茨海默症。如果想要取得进展，我们就需要更好地了解这种病的深层次原因和生物学原理。

 

• 我们需要更早地检查及诊断阿尔茨海默症。由于最终确诊阿尔茨海默症的唯一方法是通过死亡后的尸检，我们很难在病程早期就准确地识别出这种疾病。虽然有认知测试这种方法，但结果往往变动很大。如果你前一晚没睡好，这可能会影响你的结果。如果有一种像验血一样更加可靠、价格可负担和容易获得的诊断方法，我们就能更容易地了解阿尔茨海默症的进展和追踪新药物起作用的方式。

 

• 我们需要更多对抗疾病的方法。一种阿尔茨海默症药物可能通过不同的方式预防疾病或减缓疾病发展。截至目前，大部分的药物试验都瞄准了β淀粉样蛋白和tau蛋白，这是两种造成大脑斑块和缠结的蛋白。我希望这些方法能够成功，但万一它们不成功，我们需要为科学家们提供些不一样的、不那么主流的想法。一个更加多样化的新药产品线将有助于提高发现突破性解决方案的机会。

 

• 我们需要让人们更容易地参与临床试验。创新的步伐有多快，部分取决于我们能多快地进行临床试验。由于我们对阿尔茨海默症了解不多，也没有一种可靠的诊断方法，所以很难找到处于病程早期且愿意参与临床试验的合适人选。招募到足够的患者可能需要数年的时间。如果可以找到一种方法来预先选定参与者并创建有效的注册体系，我们就可以更快地开展新的试验。

 

• 我们需要更好地利用数据。每当制药公司或实验室进行一项研究时，他们都会收集大量信息。我们应该用一种通用的格式来编译这些数据，以便更好地了解阿尔茨海默症如何发病、发病情况怎样受性别和年龄影响，以及遗传基因如何对患病几率造成影响。这将使研究人员更容易寻找模式和发现治疗的新途径。

 

如果我们在以上这些领域都能取得进步，我想我们就能开发出一种干预措施，从而极大地减小阿尔茨海默症的影响。我们有足够的理由对前景保持乐观：我们对大脑和阿尔茨海默症的了解正在突飞猛进地发展。我们已经取得了一些成果，但还需要做得更多。

 

我想要支持有才华的人从事这项工作。作为第一步，我向痴呆症发现基金（Dementia Discovery Fund）投资了5000万美元，这是一个致力于增加临床药物种类和发现治疗新目标的私募基金。大型制药公司中的大多数还在继续寻求β淀粉样蛋白和tau蛋白治疗方法。痴呆症发现基金是制药公司的有益补充，它支持一些初创公司去探索不那么主流的方法治疗痴呆症。

 

我所做的这笔投资是以个人的名义，而不是通过基金会。要想实现阿尔茨海默症首次被成功治愈，这或许要等十年甚至更长的时间，而且最开始的治疗也一定会非常昂贵。等到那天来临的时候，我们的基金会可能会考虑如何把它推广到贫困国家。

 

不过在开始考虑各种做法之前，我们还是需要先实现许多科学突破。所有正在研发过程中的新工具和新理论都让我相信，我们正处在一个阿尔茨海默症研发事业的转折点。现在正是加快进步的时候，从而避免让阿尔茨海默症造成的巨大损失冲击到那些无法负担高昂医药费的国家。在那些国家，阿尔茨海默症流行对财政预算的影响，足以导致整个医疗系统破产。

 

这是一个可以大幅提高人类生存质量的前沿领域。人类寿命越来越长是一个奇迹，但只有更长的预期寿命是不够的。人们应该享受自己的晚年生活，为了实现这一点我们要在阿尔茨海默症方面取得突破。我很激动能加入对抗这一疾病的战斗，同时迫不及待地想要看看接下来会发生什么。

Why I’m Digging Deep Into Alzheimer’s 

In every part of the world, people are living longer than they used to. Thanks to scientific advancements, fewer people die young from heart disease, cancer, and infectious diseases. It’s no longer unusual for a person to live well into their 80s and beyond. My dad will celebrate his 92nd birthday in a couple weeks, a milestone that was practically unimaginable when he was born. 

This fact—that people are living longer than ever before—should always be a wonderful thing. But what happens when it’s not? 

The longer you live, the more likely you are to develop a chronic condition. Your risk of getting arthritis, Parkinson’s, or another non-infectious disease that diminishes your quality of life increases with each year. But of all the disorders that plague us late in life, one stands out as a particularly big threat to society: Alzheimer’s disease. 

You have a nearly 50 percent chance of developing the disease if you live into your mid-80s. In the United States, it is the only cause of death in the top 10 without any meaningful treatments that becomes more prevalent each year. That trend will likely continue as baby boomers age, which means that more families will watch their loved ones suffer from cognitive decline and slowly disappear. Despite this growing burden, scientists have yet to figure out what exactly causes Alzheimer’s or how to stop the disease from destroying the brain. 

I first became interested in Alzheimer’s because of its costs—both emotional and economic—to families and healthcare systems. The financial burden of the disease is much easier to quantify. A person with Alzheimer’s or another form of dementia spends five times more every year out-of-pocket on healthcare than a senior without a neurodegenerative condition. Unlike those with many chronic diseases, people with Alzheimer’s incur long-term care costs as well as direct medical expenses. If you get the disease in your 60s or 70s, you might require expensive care for decades. 

These costs represent one of the fastest growing burdens on healthcare systems in developed countries. According to the Alzheimer’s Association, Americans will spend $259 billion caring for those with Alzheimer’s and other dementias in 2017. Absent a major breakthrough, expenditures will continue to squeeze healthcare budgets in the years and decades to come. This is something that governments all over the world need to be thinking about, including in low- and middle-income countries where life expectancies are catching up to the global average and the number of people with dementia is on the rise. 

The human cost of Alzheimer’s is much more difficult to put into numbers. It’s a terrible disease that devastates both those who have it and their loved ones. This is something I know a lot about, because men in my family have suffered from Alzheimer’s. I know how awful it is to watch people you love struggle as the disease robs them of their mental capacity, and there is nothing you can do about it. It feels a lot like you’re experiencing a gradual death of the person that you knew. 

My family history isn’t the sole reason behind my interest in Alzheimer’s. But my personal experience has exposed me to how hopeless it feels when you or a loved one gets the disease. We’ve seen scientific innovation turn once-guaranteed killers like HIV into chronic illnesses that can be held in check with medication. I believe we can do the same (or better) with Alzheimer’s. 

I’ve spent considerable time over the last year learning about the disease and the progress made to date. There’s a lot of amazing work being done in this field to delay Alzheimer’s and reduce its cognitive impact. What I’ve heard from researchers, academics, funders, and industry experts makes me hopeful that we can substantially alter the course of Alzheimer’s if we make progress in five areas: 

• We need to better understand how Alzheimer’s unfolds. The brain is a complicated organ. Because it’s so difficult to study while patients are alive, we know very little about how it ages normally and how Alzheimer’s disrupts that process. Our understanding of what happens in the brain is based largely on autopsies, which show only the late stages of the disease and don’t explain many of its lingering mysteries. For example, we don’t fully understand why you are more likely to get Alzheimer’s if you’re African American or Latino than if you’re white. If we’re going to make progress, we need a better grasp on its underlying causes and biology. 

• We need to detect and diagnose Alzheimer’s earlier. Since the only way to diagnose Alzheimer’s definitively is through an autopsy after death, it’s difficult to identify the disease definitively early in its progression. Cognitive tests exist but often have a high variance. If you didn’t sleep well the night before, that might skew your results. A more reliable, affordable, and accessible diagnostic—such as a blood test—would make it easier to see how Alzheimer’s progresses and track how effective new drugs are. 

• We need more approaches to stopping the disease. There are many ways an Alzheimer’s drug might help prevent or slow down the disease. Most drug trials to date have targeted amyloid and tau, two proteins that cause plaques and tangles in the brain. I hope those approaches succeed, but we need to back scientists with different, less mainstream ideas in case they don’t. A more diverse drug pipeline increases our odds of discovering a breakthrough. 

• We need to make it easier to get people enrolled in clinical trials. The pace of innovation is partly determined by how quickly we can do clinical trials. Since we don’t yet have a good understanding of the disease or a reliable diagnostic, it’s difficult to find qualified people early enough in the disease’s progression willing to participate. It can sometimes take years to enroll enough patients. If we could develop a process to pre-qualify participants and create efficient registries, we could start new trials more quickly. 

• We need to use data better. Every time a pharmaceutical company or a research lab does a study, they gather lots of information. We should compile this data in a common form, so that we get a better sense of how the disease progresses, how that progression is determined by gender and age, and how genetics determines your likelihood of getting Alzheimer’s. This would make it easier for researchers to look for patterns and identify new pathways for treatment. 

By improving in each of these areas, I think we can develop an intervention that drastically reduces the impact of Alzheimer’s. There are plenty of reasons to be optimistic about our chances: our understanding of the brain and the disease is advancing a great deal. We’re already making progress—but we need to do more. 

I want to support the brilliant minds doing this work. As a first step, I’ve invested $50 million in the Dementia Discovery Fund—a private fund working to diversify the clinical pipeline and identify new targets for treatment. Most of the major pharmaceutical companies continue to pursue the amyloid and tau pathways. DDF complements their work by supporting startups as they explore less mainstream approaches to treating dementia. 

I’m making this investment on my own, not through the foundation. The first Alzheimer’s treatments might not come to fruition for another decade or more, and they will be very expensive at first. Once that day comes, our foundation might look at how we can expand access in poor countries. 

But before we can even begin to think about how we do that, we need lots of scientific breakthroughs. With all of the new tools and theories in development, I believe we are at a turning point in Alzheimer’s R&D. Now is the right time to accelerate that progress before the major costs hit countries that can’t afford high priced therapies and where exposure to the kind of budget implications of an Alzheimer’s epidemic could bankrupt health systems. 

This is a frontier where we can dramatically improve human life. It’s a miracle that people are living so much longer, but longer life expectancies alone are not enough. People should be able to enjoy their later years—and we need a breakthrough in Alzheimer’s to fulfill that. I’m excited to join the fight and can’t wait to see what happens next. 

If you want to receive updates on how I’m getting involved in the fight to stop Alzheimer’s disease, click on the link below and sign up to become a Gates Notes Insider.