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.
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.
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."
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.
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.
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.
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.
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.
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.