(40)预防研究-PREVENT Study-公开课-关爱惟士
(40)预防研究-PREVENT Study

课程视频:http://player.youku.com/embed/XMzY0NDE1ODEzMg


Professor Karen Ritchie

Karen Ritchie 教授


The idea of PREVENT study was to try and go back in time to take people who are at high risk; high risk because there's Alzheimer's disease in a parent - they're probably currently caring for a person with Alzheimer's disease - and because perhaps they have one of the at-risk genes, which is in this case the apolipoprotein E gene - there is a variant of this called the epsilon 4 - and that we can look at this quite easily.

“预防”研究是尝试在疾病发生之前,帮助那些父母是阿尔茨海默病患者的高风险人群,他们可能目前正在照顾阿尔茨海默病病人—而且他们也携带高风险基因,在这里指的是APOE基因—它的一种变异体我们称为epsilon 4—这样描述会帮助大家容易理解一些。


If you have this gene, it doesn't necessarily mean that you're going to get Alzheimer's disease but you're at a bit higher risk, and this is a way of helping us to find a population who might not in the end get Alzheimer's disease but they're pretty high risk, and they're certainly the sort of people one would want to work with if you were trying to do something to prevent it.

如果你携带这个基因,并不意味着你未来一定会患有阿尔茨海默病,只是说你存在高危风险,同时这也作为一种方法来帮助我们找到那些携带高风险因素最终却没有患有阿尔茨海默病的人群,对于那些想进行相关疾病预防研究的学者来说,这部分人肯定是他们希望进行研究的对象。


To set up the PREVENT study, we spoke with a number of scientists. We spoke with people in imaging and in genetics and many fields, but we also spoke a lot with people who had Alzheimer's disease in the family about their experience, so this was really the background to designing the study. And the final study design - we started in West London because Craig [Professor Craig Ritchie] was a clinical psychiatrist there and it was very near to where we were working in Imperial College in London at the time. We were also interested in West London because it had a large population of Indian-Asian origin and these people seemed to have more commonly the risk factors such as diabetes, obesity and high blood pressure. And we decided who we wanted to see were people between the ages of 40 and around 70, no older, no younger, and that we started off by contacting the people who had been on a register because they had been recently diagnosed. And on this register we also had the names of their children, their adult children, and we contacted the adult children and we said, "We're trying to look at ways in which we can change lifestyles and intervene so that people who are at some risk of developing this disease later on will be less at risk."

为了开展“预防”研究,我们同大量科学家进行了交流。我们同许多影像学,基因学等诸多领域的学者进行了对话,我们也同大量阿尔茨海默病患者家人进行沟通,这是我们设计这项研究的背景。最终的研究设计—我们选择在西伦敦进行,因为Craig 教授是一名临床精神病专家,并且距离当时我们在英国帝国学院的工作地点非常近。我们都对西伦敦很感兴趣,因为在西伦敦居住着大量的印度后裔,这些人似乎都有着很多常见的风险因素,像糖尿病,肥胖和高血压。然后我们决定观察这些介于40-70岁的人群,既不是年轻人也不是老人。我们从那些已经最近被确诊且记录在案的病人开始,记录上也有这些病人子女的联系方式,我们联系了他们的成年子女,我们对这些子女说:我们试图通过改变生活方式和干预的这样的模式,使那些处于高危风险的人群,降低他们未来的患病风险。


So they were very, very keen and probably because many of them were very frightened. They were currently caring for someone with Alzheimer's disease and they wanted to know what can we do. And I think it was important to explain at that point in time that we weren't coming to them because we thought they were going to get Alzheimer's disease; we were coming to them because we thought they probably had more of a chance than other people in the population and, given their younger age, that there were things we could do perhaps that would lower their risk even further, so, with a bit of luck, they would never get it or, if they did, it would be much later on in life, and this explanation was fairly important.

他们很乐意合作,可能因为他们中大多数感到非常害怕。他们目前正在照顾一些阿尔茨海默病病人并且他们很想知道我们能做什么。我认为这个时候跟他们解释我们来到他们身边不是因为他们一定会患上阿尔茨海默病,这一点非常重要。我们来到他们身边是因为他们比普通人群有很大可能性患此疾病,因为他们年轻,所以存在更多的可能去帮助他们在将来降低他们患上这个疾病的风险,幸运的话,他们永远都也不会患这个疾病,即使他们不幸患病,也可能是在他们生命的后期,所以做出以上这样的解释相当重要。


So there's been a tremendous enthusiasm by these people, so in West London we recruited 200 people. Half of these people have a parent with diagnosed Alzheimer's disease dementia and the other half don't have any family history. But we also looked at their genetic predisposition and we found that around 70% of the people who have a family history also have a slight genetic disposition and this compared to only 30% in the group without a family history. So they're a vulnerable group but it's not an inevitable group in terms of developing the disease.

因此,这些人对这项研究怀有极大的热情,我们在西伦敦招募到了200个人。其中一半人的父亲或母亲已经被确诊为阿尔茨海默病,而其他一半人没有家族病史。我们研究了他们的遗传易感性,发现大约70%有家族病史的人群有轻度遗传倾向,相比之下,没有家族史的人群中只有30%有轻度遗传倾向。所以他们是患此疾病的弱势群体,但并不是说他们患病不可避免。



Now, one of the challenges of this is that we know some of the things we're looking for. We know about amyloid building up in the brain. We know about tau proteins in neurons and we're going back to see if some of these things are there already. The hardest thing is looking at the effect on the cognitive functions because theoretically these people are performing extremely well. They have no problem. They maybe never will have, because there are also people who develop Alzheimer's disease in the brain, and we see it because they have an autopsy for another reason because there's a car accident, but in everyday life there was no dementia. So, the relationship between what's happening in the brain and the way we function in everyday life isn't the same for everybody. So now we're going back and we're looking at people who are much younger. If they develop Alzheimer's disease, it might not be for another 30 or 40 years.

现在其中的一个挑战就是我们需要找到一些物质。我们知道大脑中会生成淀粉样蛋白,也知道神经元中的tau蛋白,所以我们回头去看这些物质是否早已存在大脑中。最难的事是观察这些物质对认知功能的影响,因为理论上来说这些人行为表现已经很好了。他们没有什么毛病,他们可能永远也不会有,可是有的人大脑已经有了阿尔茨海默病病理变化但是在他们的日常生活中却并没有出现相关认知症表现,我们能知道这些是因为有人在车祸中死去,所以我们有机会解剖他们的尸体。所以,每个人在大脑中发生的改变跟他在日常生活中的行为表现的关系是不一致的。现在我们去观察那些年轻人,如果他们发展成了阿尔茨海默病,那可能需要30-40年的时间。


So, we started to work on not just the usual memory tests; we give these as well of course, but these are tests which for us will be too late, they're the tests we use with people who are showing signs of dementia. What we want to pick up is something far more subtle and so we've developed tests where we ask people to navigate in space.  We do this with a computer, they have to find their way, they have to recognise where they are. And eventually we'll go on to just doing virtual reality scenarios; we'll ask people to wear a mask and they'll find their way through a landscape. And we believe that we'll start to see some difficulties and, when I say difficulties, it's not necessarily the person can't do it but it'll be a bit harder, they'll take a bit more time, and we think there we'll be able to see some effect, but, of course, this won't affect their everyday functioning in any way.

我们不仅仅是从普通记忆的检测开始,我们当然会做这些检测,但这些检测对我们来说太滞后了,它们是用来测试那些已经表现出认知症症状的人群的。我们要选择的检测要更加精准,我们研发了一种关于空间定向的检测方法,我们在电脑上进行操作,受试者必须找到路,他们必须识别出他们在哪儿。最终我们会在虚拟现实场景中进行,我们会要求他们带上面罩,根据景观找到路。我们相信我们会遇到一些困难,当我说到困难,它不是指受试者不能做到,而是指对受试者来说有一定的难度,他们可能需要的时间长一些,我们认为基于此会产生一些效果,当然,这无论如何不会影响到他们日常生活的功能。


So, the first thing that the PREVENT study is going to do is we're looking at these young, much younger, well-functioning people, and we're looking at what their brains can and can't do and are there any differences that we can detect already.  We're looking at are there any differences in terms of the way they treat information when they're trying to memorise things or they're trying to reason. And we need these first measures because we as researchers aren't going to live long enough to follow these people for the next 40 years to see if they develop dementia or not. We need far more subtle early markers, as we call them, or early signs to be able to judge whether or not what we decide to do is actually working or not. So, we're in the first stage of the study at the moment where we're actually observing these people and seeing what are the differences that we can see at these early stages that we will use later to measure the effect of any sort of intervention, any sort of drug therapy that we try to introduce.

所以,关于“预防”的研究第一件要做的事就是观察这些年轻的,或更年轻的,身体功能良好的人,我们研究他们的大脑有什么功能,没有什么功能,以及任何我们已经能够检测出的差异不同。我们观察这些差异是基于被观察者试图记住事情或进行推理时他们处理信息的方式的不同。我们需要进行这些初步测量指标,因为作为研究人员我们不可能活得足够久到在未来40年内去跟踪这些人,去观察他们是否会发展成认知症。我们需要更精准的早期标记物,或者我们称之为早期信号,能够判断我们所做的事实际上是否有效。因此,我们处于研究的第一阶段,这个阶段我们所观察这些人以及在早期阶段可以看到哪些差异,会在以后用它们来衡量各种类型干预的效果及我们所推荐的各种药物疗法。


The second stage of the PREVENT study will be for us to design an intervention strategy. It will depend on what we find in the first stage in terms of how we measure this, but our intervention strategy will probably focus mostly on lifestyle factors, what we already know makes people a little more at risk. For example, what we call the cardiovascular factors - overweight, hypertension, diabetes. These factors we will focus on, also intellectual stimulation, also exercise programs. So we will design an intervention for the people in the study and we will then observe what happens across time when people adopt these lifestyle changes. Or, at a later stage there may be a drug intervention and we will use these observations of these very early changes to measure the impact of these.

第二阶段“预防”研究将设计一个干预方案。它建立在我们在第一阶段中的发现的基础上,但我们的干预方案可能更多地会关注生活方式相关因素 — 那些我们已经熟悉的增加风险的因素。比如,我们称为的心血管因素—超重、高血压、糖尿病。这些因素我们都会关注,还有智力刺激,还有锻炼计划。所以我们会在研究中设计一个干预方案,我们会全程观察人们改变生活方式时,会发生什么。而在晚期可能会有药物干预,我们会使用早期测量指标来评估药物干预的结果。


So, we won't be setting out in the first instance to cure people. What we'll be trying to do is saying here is a group at high risk and here is a group at low risk and, by intervening, can we lower the high risk group down to that of the low risk, so that they've got the same risk as anybody else.

所以,我们不是设定为第一步就去治愈认知症病人。我们尝试做的是既有高风险患病群体,也有低风险患病群体,而且经过干预,我们可以将这些高风险群体的风险降低到低风险群体的风险,这样每个人的患病风险就都一样了。

翻译:关爱惟士-未经允许不得转载,违者必追究法律责任

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