Associate Professor Michael Valenzuela
Computerised brain training, or I’ll just call it brain training, involves doing repetitive cognitive exercises, over and over again, on computer. As you get better, the exercises become more challenging, so that over time you’re improving your abilities on these different exercises. So, the analogy is kind of the brain gym. The same way you go to the gym and exercise different muscle groups, [with] brain training on computer, you’re exercising different cognitive skills, which over time lead to benefits.
计算机化的大脑训练，或者我将其称为大脑训练，涉及在计算机上一遍又一遍地进行重复的认知练习。 随着你做得越来越好，练习变得更具挑战性，所以随着时间的推移，你在这些不同的练习中提高你的能力。 所以，这种大脑训练就好比是在健身房中锻炼大脑。 在电脑上进行大脑训练，就像你去健身房锻炼不同的肌肉群，你正在以同样的方式锻炼不同的认知技能，随着时间的推移，从而获得好处。
There’s enormous interest in brain training all around the world, and one of the more recent contributions, from my group, was trying to make sense of the hundreds of studies in the area. We decided to focus on clinical trials, and we integrated the findings from more than 50 clinical trials, thousands of individuals, and there was very clear evidence that brain training, as a whole, is effective for cognitive function in older people free of dementia, but also that there are some factors that are very important and determine those outcomes.
我们对世界各地的大脑训练有极大的兴趣，我组最近的一项贡献是试图理解该地区的数百个研究。 我们决定专注于临床试验，我们整合了来自50多个临床试验，数千个人的研究结果，有非常清楚的证据表明，大脑训练作为一个整体对于老年人免于认知症的认知功能是有效的， 但也有一些因素是非常重要的，并决定这些结果。
One of the factors that really jumped out at us in this analysis, as being critical to the effectiveness of brain training, was the context or how you were doing it. If you were doing it at home by yourself, unfortunately there was no consistent effect. We didn’t really see any improvement in those individuals above the type of placebo. If you were doing it in a centre under supervision, we found that the effect was quite robust. So I think the analogy is like, if you were to go to a gym for the first time, would you be expected to use the equipment in a useful way? Probably not. I think it’s really important to have someone there, particularly at the beginning, to introduce you to this technology and then get the most out of it.
在这个分析中真正跳出来的因素之一是，对大脑训练的有效性至关重要的是内容或你是如何做的。 如果你在家里自己做，不幸的是没有一致的效果。 我们没有看到这些个人以上的安慰剂类型的任何改善。 如果你在一个中心里有人监督的情况下做的话，我们发现效果是相当强大。所以我认为做个类比，如果你第一次去健身房，你会被期望以一种有用的方式使用设备？可能不会。 我认为真正重要的是，特别是刚开始，能有人在这里向你介绍一下这个技术，然后你充分利用它。
What the evidence shows in terms of cognitive training and cognition in older people, is that it is effective on general cognitive outcomes and in specific cognitive areas, if you’ve been doing it in a supervised environment. In that case, we know that it’s effective during, and up to, stopping training. What is unclear is that, if you stop training, how long those benefits can persist. And obviously, if we’re talking about dementia, we’re talking about risk for many number of years. So we don’t know yet whether cognitive training, or brain training, can lower your risk for dementia or the development of dementia. That’s for future studies. But we can say that it’s good for your cognitive health, in older people, and we’re also starting to understand what are the brain changes triggered by so-called brain training.
So what happens in the brain, in different types of brain training, is quite a new area, because we need to combine clinical trials in brain training with neuroimaging, to understand what’s changing inside our brains. We just recently completed a study that looked at this very topic. It was called the SMART trial. And what the SMART trial shows is that, if you’re doing brain training as an older person, it increases the connectivity between two important parts of the brain. One is the hippocampus, the memory centre, and second is the frontal lobe, which is the planning and problem- solving part of the brain. It strengthens that connectivity, and that strengthening of a connectivity was related to, and even explained, the improvement in memory function in those individuals. So we’re starting to get an idea of, not just that brain training can be effective for cognitive function, particularly memory, but also the type of neuroplasticity that may be underlying that.
所以，在不同类型的大脑训练中，在大脑中发生的事情是一个新的领域，因为我们需要将脑训练中的临床试验与神经影像学相结合，以了解大脑中发生了什么变化。 我们刚刚完成了一个这类主题的研究。 它被称为SMART试验。 SMART试验显示，如果你像大人一样进行大脑训练，它会增加大脑两个重要部分之间的连接性。 一个是海马，记忆中心；第二个是额叶，这是大脑的规划和解决问题的部分。 它加强了连接性，并且解释了连接的加强与那些个体的记忆功能的改善相关， 因此，我们开始得到一个想法，不只是大脑训练可以有效的认知功能，特别是记忆，但也可能是潜在的神经可塑性的类型。
I think this is kind of a bit of a golden age for brain training, because we’re getting past the question, “Does it work?” to “How does it work, how can we make it work better?” So I think there will be a lot of interest in imaging studies, to understand mechanisms of change, and looking at the potential and limits of neuroplasticity, from this intervention, and also, how we can actually implement it in the broad scale out there in the community, to deliver real-world outcomes, like delaying dementia, or like slowing the progression from, say, being at home independent to being in an institution, so I think there’s that applied very real-world research, and also basic science understanding of the mechanisms.
Associate Professor Mathew Summers
The design of the Healthy Brain Project is to look at older adults over the age of 60, who re-engage in further education at university, and compare them against the same age group of adults who don’t engage at university. We will then assess and monitor their cognitive functions every year, for the next 10 to 20 years, the idea being to see whether that intake of doing some university education in older age, protects against later cognitive decline and possibly dementia.
The Healthy Brain Project’s unique because, as far as we’re aware, it’s the only study in the world looking at education interventions with older adults. Previous studies have looked at the effect of education in young adulthood and in midlife, but no-one’s deliberately looked at an experimental trial where we apply education to older adults.
Our participants in the study are doing all sorts of courses at university. They’re doing undergraduate courses, across a range of disciplines, be that Arts, Creative Arts, Social Sciences. There are also students doing Science degrees. We also have a number of students doing postgraduate studies, both at Masters and Doctoral PhD levels, and we’ve had a number who have already graduated, both with undergraduate degrees, in law. We’ve had students graduate with their PhDs and Doctorates already.
我们的研究参与者正在大学里学习各种各样的课程。 他们有的正在进行本科课程的学习，跨越艺术，创意艺术，社会科学一系列学科。 还有的学生在攻读科学学位。 我们还有一些学生在进行硕士和博士学位的学习，我们有一些已经毕业，拿到法律本科学位。 我们也有学生已经博士毕业。
The reason we’re using university education as a means of cognitive stimulation is more than just the education component, more than just learning new information. Universities are a community, and there’s a lot of social interaction engagement that goes on within the university setting, both within the classroom and outside of the classroom. So for an older adult who may be retired, and has lost the stimulation of a workplace, going back to university re-engages them both socially, as well as intellectually, with a group of peers from all different age groups, and that sort of stimulation is what we call complex mental activity, because it’s more than just cognitive stimulation.
I think people might have their own subjective beliefs that certain subjects are more valuable than others. For the purposes of what we’re looking at, I don’t think that that’s likely to be true. The nature of the course, or the type of subject that you study, is probably less relevant than the amount of effort that you engage in, in doing that course. So the challenge becomes more important than the subject. If you do a subject in an area that you’ve been doing for 40 years professionally, you’re probably not going to put as much mental effort in, as if you pick up a subject you’ve never done before, and actually have to learn it from scratch.
我认为人们可能有自己的主观信念，认为某些科目比其他的更有价值。 为了我们正在观察的目的，我不认为这可能是确实如此的。 课程的性质，或你学习的科目类型，可能不如你参与那个课程付出努力的大小。 因此，挑战变得比科目更重要。 如果你在学习一个科目是在你的40年的职业专业领域里的，你可能不会投入更多的心理上的努力，就像你拾起一个你从来没有学过的科目，实际上你 要从头开始学习。
In terms of how much study do you need to do to get a benefit from the impact of study, we hypothesise that there is probably a dose-dependent effect, that the more study you do, and the more engagement you do, the more protection that that would exert. It is a hypothesis, and part of the Healthy Brain study is to test that hypothesis: is that actually true, and what’s a sufficient dose, and does the amount of dose of education that a person needs vary across individuals in some systematic way?
Our participants are long-suffering volunteers in the study, and we do put them through an exhaustive assessment process. So we assess all ranges of cognitive functions, both intellectual processing capacity; we’ll look at memory and new learning; we look at executive function, such as decision making, planning, and speed of information; we look at attention and language. The range of assessments that we cover, being comprehensive, takes three to four hours of testing to get through, and is equivalent to what a full, comprehensive clinical neuropsychological assessment of an individual would do. So, for each of our participants who take part in the study, they get an annual check-up of all their cognitive processes.
在我们的研究中，参与者是长期受影响的志愿者，我们把他们放在一个详尽的评估过程中。 因此，我们评估所有范围的认知功能，智力处理能力; 我们将看看记忆力和新的学习能力; 我们看看执行功能，如决策，规划和信息处理的速度; 我们看看注意力和语言。 我们涵盖的评估范围非常全面，需要三到四个小时的测试才能完成，相当于一个人全面的临床神经心理学评估。 因此，对于参与研究的每个参与者，他们都会对所有的认知过程进行年度检查。
Alongside all the cognitive testing that we’re doing, we are collecting genetic information and samples from every participant. Now that information, the DNA that we collect, enables us to look for genetic markers. Some of the key genetic markers that we’re looking for are known to be conveying risk factors for dementia, such as the APOE e4 gene. So we assess the genetic status of all our participants and that information is then combined with all the information that we’re collecting longitudinally from these participants, and we can then determine whether the education influence that we’re applying, somehow mediates or moderates or changes the risk factor associated with each genetic component.
除了我们正在做的所有认知测试，我们收集每个参与者的遗传信息和样本。 现在，我们收集这些DNA信息使我们能够寻找遗传标记。我们正在寻找的一些关键的被认为是输送认知症的风险因素的遗传标记，如APOE e4基因。 因此，我们评估所有参与者的遗传状态，然后将这些信息与从这些参与者纵向收集的所有信息相结合，然后我们可以确定我们应用的教育影响，以某种方式调解或调节来改变与每个遗传组分相关的危险因素。
The key results so far, in the Healthy Brain study, are in the early stages of the study. So we’re into four and five years of the study, of a study that should take 10 to 20 years to complete. But our preliminary results are really exciting, in that we’ve shown in the adults that have gone to university, 92% have shown an increase in language processing ability. That’s things like word knowledge and vocabulary and comprehension, the ability to use language to communicate. We’ve shown no change in other cognitive functions, such as working memory or learning. Whereas when we look at our control group, the increase in these functions is nowhere near the same. So there’s a significant improvement in language processing. That’s exciting, because what we’ve demonstrated is there is a clear increase in cognitive processing capacity following education, in older adults. As I’ve said, it’s very early. We’re still waiting, and we need to wait another 10, possibly 20 years, to see whether that then changes the long-term trajectory. We would expect, over time, as people age, cognitive functions slow. What we’re hypothesising, given this improvement that we’ve seen in the first four to five years, the rate of slowing may change in those people, so that by the time they’re in their seventies and eighties, there should be a noticeable difference now between those older adults who went to university and their controls who didn’t.
The implications, if we find what we hypothesise, that education protects against age- related decline, are actually quite significant. Education is a non-pharmacological intervention. It conveys, in and of itself, no risk to the individual. There will be no harm, from going to do further study, to the individual, and no potential side-effect from that. So, if the only side-effect is that you reduce your age-related decline, over the long-term in the 10 to 20 years, less age-related cognitive decline means improved cognitive performance. That then improves your capacity to function independently, to remain an independent adult, part of the community, and needing less support services. There are significant economic implications to our healthcare system and to our aged care system, if we can maximise the potential of every older adult to remain independently living, with minimal support services.
如果我们发现，我们所假设的教育保护免受年龄相关的、认知功能下降的影响，实际上是相当重要的。 教育是一种非药物干预。 它本身的传达对个人没有风险。从做进一步研究到个人，都没有任何伤害，没有潜在的副作用。 所以，如果有，唯一的副作用是你在长达10到20年，里减少你的年龄相关的认知功能下降，更少的年龄相关认知下降意味着提高认知表现，这将提高您独立生活的能力，保持成年人的独立性，仍然是社区的一部分，并需要较少的支持服务。如果我们可以最大限度地发挥每个老年人的潜力，以便保持独立生活和需要最小的支持服务，这将对我们的医疗系统和老年护理系统有重大的经济影响。
When we look at the research that’s been done to date, looking at cognitive stimulation in mid to late life, the evidence isn’t great, that there’s a clear benefit. Part of the reason we’re doing the Healthy Brain Project is to find that evidence. Do we actually have a beneficial effect? At this stage, the advice I would give to anyone who’s an older person whose thinking about, “Should I do this to help me?” is fairly simple. It can’t hurt. It’s not a pill. It’s not a medication. It has no side-effect. And even if it doesn’t change the trajectory of age-related decline, even if it doesn’t delay dementia, the benefits from education, in terms of learning new material, and the intangible benefits of finding new social groups, of socialising with people from different age groups and different backgrounds, can be far greater than any change to age-related cognitive decline.
当我们看看迄今为止所做的研究，看看中晚期的认知刺激，有明显的好处的证据不是很充分。我们正在做的健康大脑计划的部分原因是，为了找到更充分的证据。我们确实拥有有益的效果吗？ 在这个阶段，我会给任何 在考虑“我应该做这个来帮助我自己吗？”的老人的建议是相当简单。它不会伤害任何人。 它不是一个药丸，不是一种药物。 它没有副作用。 即使它不改变年龄相关的衰退的轨迹，即使它不会延迟认知症发病，来自教育的好处，像在学习新材料，寻找新的社会群体，与来自不同年龄组和不同背景的人交往，这些无形的好处可以远远大于任何年龄相关的认知衰退的变化。
Associate Professor Michael Valenzuela
The FINGER trial came out last year, and was one of the first large-scale studies to look at so-called multi-modal dementia prevention. So this was a trial where they preselected people who had a number of risk factors for dementia, and then they underwent a multi-modal intervention. So what that means is that it was several streams of lifestyle changes that the investigators were trying to target. They targeted physical activity, so more exercise; they targeted cognitive activity, through brain training; they tried to optimise the management of risk factors, like hypertension and smoking; and also optimised their diet. That’s why we call it multi-modal, because it was targeting many different lifestyle factors. And what the study showed was that, after two years of this type of intervention, it was successful. So those in the intervention group improved in their cognitive abilities more than the placebo group. But what is often missed in discussions of the FINGER trial, is a little bit more complicated, and a little bit more technical, but I think worth talking about, which is that the effect size was very small. And, when we’re talking about effect size, we’re talking about what was the magnitude of the difference in the intervention group versus the placebo group. When we talk about effect sizes, we’re often talking about, “Was it small, was it moderate, or was it large?”
Whether a single or multiple lifestyle intervention is the best approach for preventing dementia, we just don’t know. I think there is a question mark now whether we can just assume that combining lifestyle interventions is better than any one or the other. So we’ve really got to do the research, to compare stand-alone interventions versus multi-modal interventions. It may be the case that doing different lifestyle interventions back to back, or one after the other, may be more effective than putting them all at the same time. So I think there’s just a lot more research that has to be done.
我们只是不知道到底是单一还是多重生活方式干预是预防认知症的最佳方法。 我认为现在有一个问号，我们是否可以假设组合生活方式干预比任何一个或其他更好。 因此，我们真的要做研究来比较独立的干预措施与多模式干预措施。可能的情况是，不同的生活方式干预背靠背，或者一个接一个地进行，可能比将它们全部同时进行更加有效。 所以我认为还有很多研究需要做。
Professor Perminder Sachdev
Perminder Sachdev 教授
So, the Maintain Your Brain trial is funded by the National Institute of Dementia Research, which is run by the NHMRC, the National Health and Medical Research Council of Australia. It's a $6.5 million study, grant over five years. What has happened as a result of the FINGER trial, is there are a number of kind of ‘children of FINGER’ so to speak, there are multiple FINGER trials that are happening around the world. Similar kinds of multipronged strategy to see whether you can fix everything and reduce your rate of dementia.
Now what we wanted to do was see whether we could do this at a larger scale, at a population level. The problem with a study like that, is that if you do it at an individual level, bring everyone in, assess them, it's hugely expensive. You can actually - you will spend several million dollars just to do a few hundred people or a thousand people or so. But we thought can you upscale this to a large population level, within a reasonable budget, and that’s what we are trying to with this, in the Maintain your Brain trial. We thought okay, can we do this through the web and increasingly older people are connected to the web.
Also, we don’t want to work necessarily with very old people, we want to work with people who are middle aged or getting in to that increased risk category. Because we want to work with people who have not yet developed cognitive problems, and middle age is probably the best time to catch them. In this trial, we said okay let's have a population of several thousand, in the age range of 55 to 75. We are recruiting them in New South Wales because there is already a study, a survey that’s happening, which is called the 45 and Up Study, which has a quarter of a million people enrolled in that study. They have already collected some health data over several waves in this population. So we know a little bit about their risk factors.
We’re going to actually recruit them by email and then get them to sign up for the study, and all assessments will be done on the web. So, their detailed medical information will be obtained online, and they do cognitive testing online as well. There are cognitive batteries available that can be done online. Then they do three or four modules, and we have been developing these modules to deliver physical exercise, complex cognitive activity, diet and nutrition, and stress and depression management on the web. These are 12-week courses that we developed and there is some evidence that this can be done. Of course, we have some personalised interactions, so there are virtual coaches, there are some cut offs that we use for alerting feedback, we send messages, text messages, put them in to virtual groups to try to engage them. All those activities have been built in to the platform.
They will have these three or four modules administered in the first year and then they'll have boosters happening every quarter, for each of those modules as they go forward. We assess them every year and we have funding for five years, so we’re hoping to at least have four years of assessment, to see whether we have reduced their rate of cognitive decline. We have enough numbers to see whether we actually cut down the incidence of dementia as well in this group. We have a control group, so they’re randomised via an active participant group and a control group, and the control group also logs in and they do some activities online, but usually they watch videos for example about health, about general, National Geographic videos, those kind of videos, which we previously used in control studies of this kind.
We were funded in 2016 and in fact mid 2016 is when we started developing the platform. Later part of 2017, we did some of the pilot work and from that we've gone back and modified some of the modules, and now we are going through the pilot phase of running all the modules in a subgroup of people, to see what kind of difficulties we might get. If that runs smoothly, then of course we are hoping to start the trial in 2018.
There has not been an online trial which actually has - which is multimodal of this kind really. There have been a lot of online trials now, which have looked at one or other aspect of say, for example, with physical exercise there have been some online trials, there have been online trails for cognitive activity, for nutrition there have been online trials, certainly for depression and stress management there have been many trials. But trying to put them all together, I don’t think there has been any trial like that, and certainly this will be one of the largest. The other aspect is I think the testing, we are doing online testing and we’re not doing face to face assessments in any of these people. Most other trials have done face to face assessments at baseline and follow up. They've been short trials really, not of this duration. So, this is a very ambitious trial in that sense, to see whether this can be delivered at a population level, at a large scale level, remotely and at low cost.
I think there are a number of concerns that we do have. The first concern of course is that there are many older people who are not online, and that can be about a third perhaps of very old people who are not online. Although that number is shrinking gradually, but still there are many people. Then there are other people who are online but they're very limited in their connectivity, in how comfortable they are with online activities, so they will need some extra help, some instruction. The third thing is that engaging people online, because interpersonal engagement, that face to face engagement is a different thing to engagement online. Certainly, younger people are easy to engage online, they've grown up with technology. But older people are somewhat more difficult, because they relate better to a person rather than to a virtual person in a way. That’s something that I think still we are working through and there’s not enough data, to convincingly show that yes, it’s as good as having a person there.
Previously in many of our trials, we have actually brought people in, for example for physical exercise. In the last trial we did, we brought them in to a gym and there was a gym instructor who worked with a group. That seems to work quite well, but it’s very expensive and it’s time consuming for everybody. Those are the concerns and there is some evidence that yes, you may be able to engage people initially, but then there’ll be a big drop out, and we don’t know how big that drop out is going to be over the course of the trial, which is running for several years.
I think once we have a platform, that it can be scaled up to a population level, to the whole population really. Because finally I think the ultimate objective would be that everybody at risk - and all of us are at risk of dementia. As we know by the time we reach our 90s, one in three people will have dementia and by the time - if you reach the age of 100, you have more than 50% chance of having dementia, so all of us are at risk for dementia. In fact, these risk factors apply to some degree to all of us in a way, so everyone should be doing what we are doing in this trial. But how we reach everybody in the population is the challenge, and if we have a platform like that, the objective would be to reach the whole population. It could be scaled up quite easily if it works. So, let’s hope the trial runs smoothly and that we’re able to recruit the number of people that we want to.
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.
Professor Carol Brayne
Carol Braune 教授
The Cognitive Function and Ageing Studies started in the late '80s as a result of the Department of Health and the Medical Research Council in the UK being concerned about the ageing population. They're population-based and they include people in care settings. They use the population registers of primary care, so they're geographically defined, and they are in different parts of the United Kingdom to represent different aspects of exposures to potential risks for dementia. So, for example, in the north of England, where people live for shorter - they have shorter life expectancy and also higher vascular risk, so there's high stroke and so on. In the rural areas, there may be different exposures, such as to pesticides and so on.
Those studies started up and their purpose was to look at the prevalence and incidence of dementia, that is, the proportion of people who have dementia, and also the people who develop dementia over time. That allowed us also to look at risk over time because we measured risk factors at baseline and followed people. We also had a brain donation program which was linked to the study. Twenty years later, we resampled people of the same age, that is 65 and over, in three of the same geographical localities in order to test for cross-generational differences in dementia.
So from the first study, we were able to estimate what numbers of people there were in the United Kingdom who might have dementia at any one time and also what numbers of people would develop dementia in a given time period, and from the second study we were able to say whether dementia itself had changed across time.
The brain donation studies allowed us to look at the underlying neurobiology or neuropathology of dementia in relation to the measures, the in life measurements. So the major findings of the study were the age relationship of dementia, the fact that women are more at risk, that people with higher education are at lower risk, that people with stroke have roughly double the risk, and so on. So these are the sorts of broad findings that we've been able to report.
The brain findings really tested the paradigms that we have of dementia and show that it's more complicated than the simplistic view which is understood by most of the biomedical community, of Alzheimer's disease tau and beta amyloid plaques and tangles always being associated with dementia in life. And we found that that is not the case, that there are protective factors such as education, and the cross-generational aspect of the study showed us that dementia has declined age for age. Prevalence has declined by more than 20%. That means that age for age the risk of having dementia for an individual is substantially lower, particularly in the 75-plus age group. Incidence has also declined by 20% and that is largely accounted for by a large decrease in the incidence in men across the different generations.
Currently CFAS is funded to experiment and to bring a trial into the cohort study, which is an unusual thing to do, so we have done a lot of ethical, legal, social implication work on what it means for cohort participants to be asked whether they'd like to take part in an intervention trial. This trial is a translation of a European prevention trial which is based on internet counselling so that an individual sets their own goals for reduction of their own risk factor profile for dementia and they're supported by a counsellor, and we'll be doing a feasibility study of that in 2018.