公开课-关爱惟士
公开课
(36)大脑训练-Brain Training

课程视频:http://player.youku.com/embed/XMzY0NjIwMzI4OA



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.

在老年人的认知训练和认知方面有证据表明,如果你是在监督的环境中做的话,它对一般认知结果和特定的认知领域有效。在这种情况下,我们知道它在进行训练时是有效的,直到停止训练。我们不清楚的是,如果你停止训练,这些好处可以持续多久。显然,如果我们在谈论认知症,我们会谈论多年的风险。 因此,我们还不知道认知训练或大脑训练是否能降低认知症或发展认知症的风险。这是未来的研究。但我们可以说,这对你的老年认知健康是有好处,我们也开始了解什么是所谓的脑部训练引发的大脑变化。


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.

我认为这对于大脑训练来说是一个黄金时代,因为我们越过了下面问题“它工作?”到“它是如何工作的,我们如何使它的工作更好?”所以我认为将会有很多关于成像研究,理解变化机制,以及从这种干预中观察神经可塑性的潜力和局限性的兴趣,以及我们如何在社区广泛的范围内实现它,提供真实世界的结果,如延迟认知症,或者像放慢自己的进程,放松在一个机构,所以我认为这是应用于非常现实世界的研究,以及基本的科学理解的机制 。


翻译:关爱惟士-未经允许不得转载,违者必追究法律责任


塔斯马尼亚大学预防认知症MOOC
2018-06-08
(37)塔斯马尼亚健康脑计划-The Tasmanian Healthy Brain Project

课程视频:http://player.youku.com/embed/XMjY3ODM4OTc4MA


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.

健康大脑计划的设计是看看60岁以上的老年人重新进入大学继续接受教育,并与不在大学就读的同一年龄组的成年人进行对比。 然后我们将在未来10到20年,每年评估和监测他们的认知功能。这个想法是看看在较大年龄时接受大学教育的人是否能防止以后的认知衰退和患认知症的可能。


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.

据我们所知,健康大脑计划的独特之处在于,这是世界上唯一一个针对老年人的教育干预措施的研究。 以前的研究已经研究了教育对年轻的成年人和中年人的影响,但没有人特意去做一个像我们把教育应用在老年人上的试验。


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.

我们使用大学教育作为认知刺激手段的原因不仅仅是教育本身,也不仅仅是学习新的信息。大学是一个社区,在大学环境中,无论是在教室内还是在教室外都有很多社交互动参与。 因此,可能对于已经退休并且已经失去了来自工作场所刺激的老年人,回到大学重新让他们在社会上和在智力上与一群来自所有不同年龄组的人为伴,这类刺激是我们所说的复杂的心理活动,因为它不仅仅是认知刺激。


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?

依据你需要做多少研究将能从研究的影响中获益,我们假设可能有个剂量依赖的效应,那就是如果你做越多的研究,参与的越多,越多的保护效果就会发挥出来。 这是一个假说,而健康脑研究的一部分就是测试这个假说:这是真的吗,什么是足够的剂量,一个人需要的教育剂量在某些系统的方式是否因人而异?

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.

迄今为止,在健康脑研究中的关键结果是在研究的早期阶段。所以我们进入到这项需要10到20年才能完成的研究的最初的四到五年,但我们的初步结果是非常令人兴奋的,因为我们所研究的回去上大学的成年人中,92%表现出语言处理能力的增加,像文字知识,词汇量和理解力,使用语言沟通的能力。我们没有显示像如工作记忆或学习等其他认知功能的变化。而当我们看看我们的对照组,这些功能的增加是无处接近相同。因此,语言处理能力有了显著的进步。这是令人兴奋的,因为我们已经证明,老年人进行教育学习后,认知处理能力明显增加。正如我所说,这是还太早。我们还在等待,我们需要再等10年,可能是20年,看看这是否改变了长期轨迹。我们预计,随着时间的推移,随着人的年龄增长,认知功能减慢。我们假设的是,考虑到我们在前面四至五年所看到的改善,这些人的认知功能减慢速度可能会发生改变,所以当他们在七八十岁时,那些进入大学学习的老年人和他们的对照组之间应该有一个显著差异。


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。


翻译:关爱惟士-未经允许不得转载,违者必追究法律责任



塔斯马尼亚大学预防认知症MOOC
2018-06-08
(38)“FINGER”试验-The FINGER Trial

课程视频:http://player.youku.com/embed/XMjY3ODM4OTU0OA



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?”

去年出现的FINGER试验,是首次进行所谓的多模式认知症预防的大规模研究之一。这是一个预先选择的人群,他们有认知症的一些危险因素,然后他们进行多种模式干预的试验。所以这意味着研究者试图瞄准 几种生活方式的变化。瞄准体育活动,所以他们建议更多的运动;针对认知活动,他们通过大脑训练;他们试图优化高血压和吸烟等危险因素的管理;并优化了他们的饮食。这就是为什么我们称之为多模式,因为它瞄准了许多不同的生活方式因素。研究表明,它是成功的。因此,经过两年的这种干预,干预组的认知能力比安慰剂组提高。但是在FINGER试验的经常错过的讨论是,有点复杂,有点技术性,但我认为值得谈论的是效应量非常小。而且,当我们谈论效应量时,我们讨论的是干预组与安慰剂组之间差异的大小。当我们谈论效果大小时,我们经常谈论,“它是小,是中等,还是大?


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。


翻译:关爱惟士-未经允许不得转载,违者必追究法律责任

塔斯马尼亚大学预防认知症MOOC
2018-06-08
(39)维护你的大脑-Maintain your brain final audio


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.

“维护你的大脑”试验是由国家认知症研究协会资助,由NHMRC(澳大利亚国家健康医疗研究协会)来进行研究。总资金650万美元,至今已有五年之久。作为“FINGER”试验的产物,出现了很多类似“FINGER”试验的“子女”,可以说,在世界各地都进行着大量的“FINGER”试验。类似一种多管齐下的策略,看看能否解决问题并降低认知症发病率。


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.  

现在我们想做的是看看能否在人群层面更大规模地做这项工作。问题在于,如果你在个体层面上做这个研究,让个体参与进来,评估他们,那需要巨大的花费。你其实做的是—花费数百万美元却只得到几百人或者一千人的研究数据。但是我们认为可以在合理预算范围里将其提升到更高人口水平,这正是我们在“维护你的大脑”这个试验里试图去做的。我们认为没有问题,我们可以通过互联网来做,并且越来越多的老年人也在使用网络。


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.

还有,我们不需要高龄者参与试验,我们想让中年人或者高风险的人来参与。因为我们想让那些认知还没有出现问题的人们参与到试验中来,能找到问题核心的最佳年龄段是中年。这个试验,我们计划募集几千名年龄在55至75岁之间的受试者。我们在新南威尔士进行招募,因为在新南威尔士已经进行了一个称为“45岁及以上”的研究,有25万人加入到这个研究中来。此研究已经收集了一些健康数据,这样我们对这些人群存在的风险因素有了先一步的了解。


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.

我们通过邮件的形式招募受试者,然后他们需要签字同意参与这个研究,并在网上完成所有的评估。这样我们通过网络获得他们详细的医疗信息,受试者也可在网上进行认知水平测试。我们在网上提供一系列的认知训练给受试者,他们完成三或四个模块,包括体育活动,高级认知活动,饮食和营养,以及压力和抑郁管理等,我们开发了为期12周的课程,证据显示这些课程是可以被完成的。当然,我们也有一些个性化的互动,像虚拟的指导员,如果有中断的情况,我们可以提醒受试者反馈信息,我们发送信件,短信,把他们放在一个虚拟的组群里,努力让他们参与进来。所有的这些活动都已经在这个平台建立完成。


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.

在第一年他们需要完成3或4个模块,并且随着向前逐渐推进,每个模块中每完成四分之一都会有加油的进程提示。每年我们都对受试者进行评估,我们已经开始这个研究5年,我们希望至少有四年的评估数据,来确定我们究竟有没有降低他们认知下降的速度。我们有足够的数据来证明我们是否真的降低了这个年龄组中认知症发病率。我们有一个对照组,他们被随机分配在积极参与组与对照组,对照组也登录网络并进行一些在线活动,但是通常他们只观看一些关于科普健康或者国家地理等内容的视频,这些我们都曾经在以前类似研究中的对照组中使用过。


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.

2016年我们收到资助,事实上2016年中我们就开始开发这个平台。2017年后半年,我们开展了部分试点工作,随后我们对一些模块进行了修改调整,现在我们计划完成不同小组全部模块的试点工作,来观察我们可能会遇到的各种困难。如果运行顺利,那么当然我们希望可以在2018年开始这个试验。


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.

在这之前并没有真正意义在网络上进行过这样的试验—实际上是个多模式试验。现在网络上的很多试验只观察某个方面,举例说,很多在线试验是关于体力锻炼的,关于认知活动的也有,营养学方面的也不少,当然对抑郁症和压力管理的试验也不胜枚举。但是把它们放在一起,我认为目前还没有,当然这也一定是一个大型试验。另一方面,我认为我们所做的是全在线测试的形式,没有对任何人做过面对面评估。大多数的其他试验会在基线状态及随访时进行面对面评估。那些都是短期试验,不像我们的周期这么长。所以从这个意义上说这是一个很有雄心的试验,让我们看看能否在人口水平,大规模地用低成本去实现它。


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.

我们的确有一些担忧。首当其冲的担忧就是很多老年人他们不使用网络,大约有三分之一的高龄老人都不使用网络。尽管这些数字在逐渐缩小,但是还是有很多人。而那些使用网络的老人,他们上线的时间又非常有限,以及对于线上活动在多大程度能够适应,他们会需要一些额外的帮助和指导。第三个担忧就是如何使受试者能够有参与感,参与感是在人与人之间实现的,网络参与同现实中面对面参与是完全不同的。当然年轻人生在科技年代,进行线上活动对他们相当容易。但是老人却截然不同,相比虚拟交际他们更容易接受真实的人际交往。这就是我认为我们仍需努力的事情,没有足够的数据来非常信服的告诉我们,虚拟网络和现实中与人相处是一样的。


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.

早期的很多试验,我们把受试者带到试验里比如进行体力锻炼。在上一个试验中我们把受试者带到健身房,每组有一个健身教练来指导他们。看起来一切进行得很好,但是成本却很高,并且很浪费时间。这些就是我们的担忧,有证据显示,开始时一些受试者参与进来,但接着有很多人退出,我们不知道在这个周期这么长的试验期间退出的人到底会有多少。


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.

我想一旦我们有这样一个平台,那就是把规模增加到人口水平,甚至是全人类水平。因为我认为最终我们的目标是知道每个人的风险,我们所有人患认知症的风险。我们知道, 90岁时三分之一的人将会患上认知症—如果你活到100岁,你患认知症的几率将超过50%,所以说,我们所有人都面临患有认知症的风险。事实上,这些风险因素都不同程度地以特定的方式影响每一个人,所以每个人都应该做我们在试验中所做的事。但是如何覆盖到每一个人是我们面临的挑战,如果我们有了这样一个平台,那这个试验就可以覆盖到整个人类。如果有效的话,它会很容易的扩大延展。所以我们真心希望这个试验可以顺利进行下去,我们能够尽可能的招募到我们希望的人数。


翻译:关爱惟士-未经允许不得转载,违者必追究法律责任

塔斯马尼亚大学预防认知症MOOC
2018-06-08
(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

塔斯马尼亚大学预防认知症MOOC
2018-06-08
(41)认知功能与衰老研究-The Cognitive Function and Ageing Studies

课程视频:http://player.youku.com/embed/XMzY0NDE1ODg0NA




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.

基于卫生部及英国医学研究理事会关注的认知功能及老龄化的研究开始于上世纪80年代后期,研究是基于人群的研究,包括一些有医疗健康背景的人群。通过国民早期健康照护登记记录,在地理位置上我们选择了英国不同地区的群体,这些群体有不同的认知症患病风险。举例来说,生活在北英格兰地区的人普遍寿命较短—平均寿命短并伴有高危血管性风险因素,所以这个地区中风发生率高。而在农村,人们则可能面临其他不同的风险因素,比如农药中毒等。


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.

这项研究的目的是调查认知症的流行率和发病率,即了解认知症患者的占比及随着时间推移认知症患者的数量变化。随时间推移我们对风险进行观察,因为我们从基线开始确定了这些风险因素并且保持随访,我们也启动了大脑捐献项目来支持我们的研究。在二十年后,我们对上述三个地区65岁及以上的同一年龄组进行再次抽样,为了检测认知症跨年龄层的不同。


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.

从第一次的研究我们可以估计英国在某一时间认知症患者的数量,以及多少人在某个特定的时间段会发展为认知症,而从第二次研究结果中看出,认知症本身是否随着时间推移已经发生了变化。


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.

大脑捐赠项目使我们能够观察与我们评估标记物相关的潜在神经生物学及神经病理学的大脑变化。这个研究项目的主要发现是:老龄化跟认知症的密切关系,女性的风险要大于男性,受教水平高的人们患认知症的风险低于低教育水平的人们,中风患者的风险水平大约是是平常人的两倍等等。这些是我们能报告给大家的一些研究结果。


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.

大脑研究项目真正意义上检验了我们认为的认知症范式,并告诉我们它比大多数生物医学界所持有的简单观点其实要复杂很多,阿尔茨海默病tau蛋白和β淀粉样蛋白形成的斑块和缠结总是与认知症密切相关。不过我们发现情况并非都如此,我们发现高教育水平是有利保护性因素,跨年龄段研究也证明认知症发生率随年龄下降而下降,流行率下降超过20%。这意味着年龄越小,个体患认知症的概率越低,特别是75岁以上的年龄组。发病率下降20%很大程度上是因为男性在不同年龄层发病率普遍大量下降所致。


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.

目前CFAS资助了这个试验并开展了队列研究,这不是一件简单的事情,所以我们做了大量关于道德,法律和社会影响方面的工作,像询问他们是否愿意参与队列研究以及这个试验的意义。该试验是一项欧洲预防试验的另外一个版本,它建立在互联网咨询的基础上,以便参与者在咨询顾问的支持下设定自己个性化目标来减少自身认知症风险因素,我们将在2018年开展这个可行性研究。

翻译:关爱惟士-未经允许不得转载,违者必追究法律责任

塔斯马尼亚大学预防认知症MOOC
2018-06-08