公开课-关爱惟士
公开课
(8)流行病学导论-Introduction to Epidemiology

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



Professor Kaarin Anstey

Kaarin Anstey教授


In epidemiology we look at a particular health problem in terms of the population. Whereas clinicians are just focusing on an individual patient, in epidemiology we want to look at the prevalence, so how common is a particular health condition across the entire population, and at what rate does it increase. So we talk about incidence. So if we’re looking at dementia, we’d say, “how many people have dementia at this point in time?” - that’s the “prevalence.” And “over the next five years, how many people would develop dementia?” - that’s the “incidence.” And then another critical aspect of epidemiology for this is looking at “risk factors,” so things that increase the chance that a person will develop the disease that we’re studying.

在流行病学的研究中,我们是从人群水平来了解某一特定的健康问题。临床医生只是专注于个体患者,而在流行病学中,我们是要观察患病率,即在整个人群中特定的健康问题有多严重。另外还要观察它以什么样的速度在增加,所以我们谈论发病率。因此当我们研究认知症的流行病学时,我们会说,“在这个特定时间点有多少认知症患者?” - 这是指“患病率”。而“在接下来的五年中,会有多少人发展成认知症? - 这是指“发病率”。此外流行病学的另一个关键点是观察“风险因素”,就是增加一个人发展我们正在研究的这种疾病的概率。



I’m going to be talking about the types of epidemiology studies that are conducted, to answer questions of prevalence, incidence and risk. So, to get the prevalence of a disease, say dementia, we need to have a sample that we study that is representative of the population. Ideally, for example, in Australia we would take a random sample of the entire population of Australia, but we’ve got such a large land mass here that’s not possible. So we often do a representative sample of a particular region, and then we extrapolate up to the country population from that. So that’s a single, one-off survey that we could do or study. Often we want to do a longitudinal study, especially if we’re looking at risk factors. So we take a cohort and we do a longitudinal study or what’s also called a prospective study, or it’s sometimes called a cohort study. And that’s where we take this group of people who’ve been sampled randomly from a defined area or population, and we follow them over time, and we test the same people again and again and again. And we look at how their risk factors may change and whether or not they develop dementia longitudinally.

我将介绍我们已经进行的不同类型的流行病学研究,以解答有关患病率,发病率和风险方面的问题。因此为了获得例如认知症等疾病的流行情况,我们需要一个代表人群作为我们研究的样本。例如,在澳大利亚,理想状况下是对整个澳大利亚的人口进行随机抽样,但在这么大的土地面积上我们是不可能的这样做的。因此,我们通常在一个特定区域抽取一个有代表性的样本,然后从中推断出整个国家的人口情况。这是一个我们可以做或执行的单一的,一次性的调查研究。特别是如果我们在观察风险因素的话,我们通常会做一个纵向研究。因此,我们采取排队列的方法做纵向研究,或称为前瞻性的研究,或有时称为队列研究。这就是我们从一个定义的区域或人群中随机抽样组成一组人群,我们随访他们,然后一次又一次地调查同一组人群。我们观察他们的风险因素是否变化,以及他们是否会纵向发展成认知症。


How useful is an observational study or an epidemiology study in the field of dementia epidemiology in establishing a risk and causality, compared to a randomised control trial? To answer that question, we actually have to take a step back. And we have to think about the fact that dementia occurs due to pathological changes in the brain, and these occur over decades. So they’re not occurring over a very short period of time like 12 months or two years. And, so, we can’t actually conduct short-term studies on the causes of dementia at the population level; we need to have that long-term information to see who’s going to go and develop dementia. From that point of view, we’re really left with cohort studies as the main method of studying risk for dementia.

与随机对照试验相比,认知症的观察性流行病学研究能够为风险和因果关系的建立起多大作用呢?要回答这个问题,我们实际上必须后退一步。并且我们必须考虑痴呆发生是由于大脑了发生了几十年的病理变化的这一事实。因此,他们不会发生在一个像12个月或两年这样非常短的时间。因此,我们实际上不能在人群水平上对认知症的原因进行短期研究;我们需要有这些长期的信息来观察谁会患上和发展认知症。从这个角度来看,我们确实应该将队列研究作为研究痴呆风险的主要方法。


And, secondly, a number of the risk factors that have come out from the research that’s been conducted are things that we couldn’t examine using a randomised control trial methodology. I’d just better explain what a randomised control trial is. A randomised control trial is when you take a sample and you randomly allocate the members of the study to different conditions, and then because of the randomisation, you’re able to adjust for all of the potential factors that may influence the results. So, for example, you might conduct a randomised control trial of a drug that theoretically is thought to prevent dementia, and every person who came in would get a random allocation to drug, or no drug. The problem is, with dementia, again, it takes so long to develop and the brain changes take a long while to accumulate, so we couldn’t conduct a short-term randomised control trial. And, secondly, it wouldn’t be ethical to look at some of the risk factors for dementia in a randomised control trial. For example, we couldn’t ask people to smoke to see if smoking caused dementia. We couldn’t expose people to heavy air pollution, to see if that causes brain damage that’s irreversible. The sort of questions that you’d end up asking are just almost illogical and they’re completely unethical. So we really can only look at these questions using what we call observational studies, where we look at exposure just through normal life, whether the people chose to smoke, whether they lived in an area with heavy air pollution, and then we use statistical methods to try to adjust for all of those potentially confounding factors. And then we follow people up and see if those what we call “exposures,” so exposure to smoking or air pollution or heart disease of whatever, if those things increased the risk long-term of dementia.

其次,已开展的研究发现一些风险因素是我们无法使用随机对照试验方法研究的。首先我先解释什么是随机对照试验。随机对照试验是当您抽取一个样本并随机分配到不同的组别,然后由于采用了随机分配,你能够控制所有可能影响结果的潜在因素。因此,例如,您可以对理论上被认为能预防认知症的药物进行随机对照试验,并且每个纳入的人都会随机分配到给药组和不给药组。问题是认知症需要很长的时间来发展,而且大脑的变化需要很长时间的积累,所以我们不能进行短期的随机对照试验。其次,在随机对照试验中观察认知症的某些风险因素是不道德的。例如,我们不能要求人们抽烟,看看吸烟是否导致认知症。我们不能让人们遭受严重的空气污染,看看是否会导致不可逆的脑损伤。你最终要问的此类问题时几乎是不合逻辑和不道德的。因此,我们的确只能使用我们所谓的观察性研究来研究这些问题,我们只能通过日常生活状态来观察暴露,从而了解人们是否吸烟,是否居住在空气污染严重的地区,然后使用统计方法来尝试调整所有这些潜在的混杂因素。然后我们跟随这些人群,看看我们所谓的“暴露”,即暴露于吸烟,或空气污染,或者心脏病这些是否能增加认知症的长期风险。


So, the question is: how do we evaluate the results of observational studies that show, for example, factor A is a risk factor, and then a similar study in another country might find it’s not a risk factor? There’s a number of approaches to this problem. This is something that we deal with – well, I in particular in my group, at the Australian National University, deal with a lot. First of all, we look at the quality of the research design of the study that found the result, did they adequately adjust for potential confounders? Was the sample biased? How long did they follow up the sample; is it a long enough follow up? Was there a lot of sample attrition leading to sample bias? Were the measures adequate? Did they properly measure the exposure and did they have a proper measure of dementia diagnosis at outcome? So you look at all of these design issues. Was it a big enough sample to give a statistically robust result?

因此这个问题是:我们如何评估观察性研究的结果,例如,因素A是一个风险因素,而在另一个国家的类似研究可能会发现它不是这样。有很多的方法可以解决这个问题。这是我们,特别是我在澳大利亚国立大学的研究小组,处理很多这样类似的情况。首先,我们看看发现结果的研究设计的质量,他们是否适当调整了潜在的混杂因素?样本是否偏倚?他们随访了样本多久了;随访期是否足够长?失访率是否很高进而导致样本有偏倚?采取的措施是否足够?暴露测量是否恰当,并且认知症作为结果进行诊断是否恰当?所以你要注意所有这些设计要点。是否能提供一个足够大的样本从而给出统计上的可靠的结果?



So that’s the first approach, and sometimes that alone will tell you that the result is probably not reliable, because there are methodological flaws in the study or limitations that mean it’s inconclusive. Secondly, what we do in this field of dementia epidemiology is that we consider each cohort study as one study in a sample of studies, and there’s actually a population of these studies, so we assume there is a true finding of an effect. So we do something called “meta-analysis,” and that’s where we bring together all of the different studies on a particular topic. So if we took, for example, smoking, does smoking increase risk of dementia, we would get all of the published studies on smoking and risk of dementia and we’d use statistical methods to pool the results. And that gives us a robust estimate and we can actually look at something called the study bias, the selection or publication bias using statistical techniques to see if we have got a good representation of all of those studies. And, from that, we derive a much more robust estimate of the effect and a standard error around that estimate, and that’s really what we prefer to use, rather than just the result of a single study.

所以有时单独使用第一种方法--观察性流行病学研究时,由于这种研究存在方法上的缺陷或局限,结果可能不可靠。其次,我们在痴呆流行病学领域所做的是,我们把每个队列研究作为这些研究的一个样本,实际上是这些研究的某一个人群,所以我们假设每一个影响因素会有一个正确的结果。因此,我们做了一个名为“荟萃分析”的工作,也就是我们将某个主题的所有不同研究集中在一起。因此,如果我们以吸烟是否增加得认知症的风险的研究为例,我们将搜集所有关于吸烟和痴呆风险的研究的文章,我们将使用统计学方法来汇总结果。这给了我们一个可靠的估计,并且我们可以考察统计技术使用的所谓的研究偏倚,选择偏倚或发表偏倚来看看我们是否能很好的代表这些研究。因此,我们得出一个更加可靠的效果估计和拥有较小的标准误,这正是我们真正喜欢使用的,而不是仅仅一个单一研究的结果。


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
2018-05-21
(9)乳酪和认知症的假设性研究-Hypothetical Study of Cheese and Dementia

http://player.youku.com/embed/XMjY3ODMzMTYwOA



Dr Maree Farrow

Maree Farrow博士

Often we see headlines in the media that might tell us a certain behaviour will increase our risk of dementia while another behaviour might reduce our risk of dementia. Those headlines, unfortunately, can be misleading. They can leave us believing that we could eliminate our risk of dementia completely simply by eating more chocolate or drinking more coffee. But what do those headlines really mean?

我们经常在媒体上看到告知我们某种行为或许将增加我们患的认知症的风险,而另一种行为可能会降低我们的认知症风险的新闻标题。不幸的是,这些标题或许是误导性的。他们让我们相信可以仅仅通过吃更多的巧克力或喝更多的咖啡来完全消除患认知症的风险。但这些头条真正含义是什么呢?


Let’s talk about how researchers actually find out how a particular behaviour affects our risk of developing dementia. Let’s say we wanted to find out how eating cheese is related to the risk of dementia. Now it’s not, as far as we know. There’s been no studies looking at this, so please don’t worry about eating cheese. This is a hypothetical example that we’re going to use here.

让我们介绍一下研究人员是如何发现某一特定行为是如何影响我们发展认知症的风险的。例如我们想知道吃奶酪是否与得认知症的风险相关。据我们目前所知,不是这样的。 迄今没有任何研究发现这个,所以请不要担心吃奶酪。这是一个我们要在这儿使用的假设性例子。


One of the best ways to look at this question would be to conduct what we call a prospective cohort study. In this type of study, we’d recruit a random sample of people and we’d ask them how much cheese they eat. Then we’d follow them up over a number of years to determine who gets dementia, and whether how much cheese they eat was related to their risk of developing dementia. Then we would use statistics to determine whether eating cheese had a significant effect on your risk of developing dementia and also how big that effect might be.

解决这个问题的最好方法之一是进行我们所谓的前瞻性队列研究。在此类研究中,我们会招募一个随机抽样的人群,我们会问他们吃多少奶酪。然后我们会随访他们多年来确定谁会患认知症,以及他们吃多少奶酪是否与他们的罹患认知症的风险有关。然后我们将使用统计学方法来确定吃奶酪是否对罹患认知症的风险有显著的影响,以及这种影响可能有有多大。


In our hypothetical research study, we’re going to start by recruiting two thousand people who are aged over 65. We’re going to ask them how much cheese they eat and we’re going to split them into two groups. We’re going to take the people who eat more than 100 grams of cheese per week and then the people who eat less than that amount per week. So in this hypothetical study, let’s say we were able to split the group in half. So we have one thousand people who eat more than 100 grams of cheese per week. We’re going to call them the high cheese group. Then we have another one thousand people who eat less than 100 grams of cheese per week, and we’re going to call them the low cheese group.

在我们假设的研究中,我们要询问他们吃多少奶酪,从而分成两组。我们将从招募2000名65岁以上的人开始。我们将每周摄入超过100克奶酪的人放在一组,将每周摄入不到100克奶酪的人放在另一组。所以在这个假设的研究中,我们有每周摄入超过100克的奶酪的一千个人,我们称之为高奶酪组,另外还有由每周吃不到100克奶酪另外一千个人组成的低奶酪组。


To do this study well, we’d need to match our two groups on things like age and gender, the other things that they eat in their diet, and any other factors that might affect dementia risk, so that how much cheese they ate was the only thing that was different about the two groups. We would also test their cognitive function at the beginning of the study, to make sure that they didn’t have dementia at the start. After this baseline testing, we’ll follow our two thousand participants for the next ten years, and we’ll meet with them every two years to test their cognitive function, and in that way we can determine if anyone develops dementia over that time.

为了做好这项研究,我们需要匹配可能会影响认知症风险的这两个组的年龄和性别,他们在饮食中所吃的其他东西,以及任何其他因素,以便使他们吃多少奶酪成为这两个组唯一不同的地方。我们还将在研究开始时测试他们的认知功能,以确保他们在刚开始时没有认知症。在这个基线测试之后,我们将在未来十年里随访这两千个参与者,我们将每两年与他们会面以检测他们的认知功能,从而可以确定在这段时间是否有人发展为认知症。


So in our hypothetical study, let’s say we found that over the ten years 120 people developed dementia. Now 80 of those were from the high cheese group, so that represents 8% of the people in that group who did develop dementia over those ten years.

因此,在我们假设的研究中发现,十多年来有120人发展成为认知症。其中80个人来自高奶酪群,这代表该组8%的人在十年中发展成认知症。


In the low cheese group, however, there were only 40 people who developed dementia, so that represents 4% of the low cheese group.

然而在低乳酪组中,仅有40个人发生痴呆,占该组总人数的4%。


And we might start to think about whether eating cheese is such a good idea. But what do these numbers really mean? There’s two different ways we can look at the findings - depending on whether we’re interested in the effects of eating a lot of cheese or the effects of eating not much cheese.

另外我们可以开始考虑吃奶酪是否是一个好主意。但这些数字真正的含义是什么呢?我们可以有两种不同的方式来看结果 - 取决于我们是否对吃大量的奶酪或吃不太多的奶酪的影响感兴趣。


Let’s first look at how eating high amounts of cheese affects dementia risk in our hypothetical study. From our finding that 8% of people in the high cheese group developed dementia compared to 4% in the low cheese group, we can conclude that eating high amounts of cheese might double the risk of developing dementia. We could also say that eating high amounts of cheese increases the risk of dementia by 100%. Then, as researchers, we would calculate what we call a risk ratio, and in this case the risk ratio is simply eight divided by four, which is two.

让我们先来看看在我们的假设研究中吃大量的奶酪是如何影响痴呆风险的。我们发现,高乳酪组中8%的人发展成认知症,而低乳酪组的发生率为4%,我们可以得出结论,摄入大量乳酪可能会让得认知症的风险增加一倍。我们还可以说,吃大量奶酪会使患认知症的风险增长100%。然后,作为研究人员,我们将计算所谓的风险比,即8除以4,等于2。


A risk ratio of two means exactly the same thing as increasing the risk of dementia by 100% or doubling the risk through eating high amounts of cheese.

风险比率是2,意味着吃大量的奶酪使患认知症的风险增长100%或风险加倍是同一件事。


We would then use statistics to determine if our risk ratio is significant. A statistically significant risk ratio means that we can be reasonably certain there’s a real relationship between eating cheese and the risk of developing dementia, rather than it just being due to chance.

然后我们将使用统计学方法来确定我们的风险比是否显著。统计学上显著的风险比意味着我们可以合理地确认吃乳酪与得认知症的风险之间的确存在着联系,而不仅仅是由于偶然性。


To investigate the effects of eating small amounts of cheese, we would look at our results the other way around. From our results that 4% of people in the low cheese group developed dementia, compared to 8% in the high cheese group, we could conclude that eating small amounts of cheese halves the risk of developing dementia, or that the risk is reduced by 50%. And the risk ratio in this case would be four divided by eight or 0.5. So again having a risk ratio of 0.5 is exactly the same as halving the risk or reducing the risk by 50%. And once again we would need to use statistics to determine if that relationship was statistically significant.

为了调查吃少量奶酪的效果,我们将以另一种方式来观察我们的结果。我们的结果表明,和高乳酪组的8%相对比,低乳酪中的4%的人发展为认知症,我们从而可以得出结论,吃少量乳酪将减半发展成认知症的风险,或将风险降低50 %。在这种情况下的风险比率将是4除以8或即0.5。因此,再次拥有0.5的风险比率与将风险减半或将风险降低50%,含义完全相同。并且我们需要再次使用统计学方法来确定这种关系是否具有统计学意义。


Doubling your risk of dementia sounds pretty scary, while halving your risk of dementia sounds like a good idea. So would you give up eating cheese based on these findings? There are some very important points to remember when looking at research findings like this.

你患认知症的风险加倍听起来很可怕,而减少痴呆的风险似乎是一个好主意。那么你会因为这些发现放弃吃奶酪吗?看到这样的研究结果时,有一些要点需要牢记。


Firstly, although the relative risk of developing dementia was doubled by eating high amounts of cheese in our hypothetical study, the absolute risk changed by only a small amount from 4% to 8%. The other 92% of people in the high cheese group did not develop dementia, despite the fact that they consumed those higher amounts of cheese.

首先,虽然在我们假设的研究中通过摄入大量奶酪使发展为痴呆症的相对风险加倍,但是绝对风险仅从4%变为8%。高乳酪组中其他92%的人没有发展成痴呆,尽管事实上他们消耗了更多的奶酪。


Secondly, a finding like this does not mean that eating cheese causes dementia. What we found was an association between the two things, but this does not represent a causal link.

其次,这样的发现并不意味着吃奶酪会导致痴呆。我们发现的是两个事物之间的联系,但这并不代表一个因果关系。


And finally, a study like this can’t tell us everything about the relationship between eating cheese and developing dementia. What about younger people? If they ate lots of cheese would that affect their risk of developing dementia later in life? What about the type of cheese you eat? Is parmesan cheese better or worse than gorgonzola? And what about the amount of cheese you eat? If 100 grams of cheese per week increases the risk, would 200 grams of cheese per week increase the risk even further?

最后,像这样的一个研究是无法告知我们吃奶酪和发展为认知症之间的关系的一切的。年轻人会怎么样?如果他们吃了很多奶酪会影响他们生命后期发展为认知症的风险吗?你吃的奶酪是哪种类型?是帕尔马干酪比戈尔贡佐拉奶酪更好还是更差呢?你吃奶酪的数量如何?如果每周吃100克奶酪会增加风险,那么每周吃200克奶酪还会进一步增加风险吗?


What this finding means is that older people who eat more of any kind of cheese might have a slightly higher chance of developing dementia. Don’t forget though, this is a hypothetical question. So if I did eat lots of cheese, based on these findings, I might think about cutting back to reduce my risk of dementia, but I would do so knowing that it wouldn’t stop me getting dementia, and I’d also know that it was only one of many choices I could make to potentially reduce my risk of dementia.

这个发现意味着,吃更多的任何种类的奶酪的老年人可能有更大一点的发展为认知症的可能性。但是不要忘记,这是一个假设性的问题。所以基于这些发现,如果我吃了很多奶酪,我可能会考虑削减我患认知症的风险,但我知道这样做不会阻止我得认知症,我也知道它只是我可以做出的潜在降低患认知症的风险的众多选择之一。


Now what would the media make of these findings? We might see headlines such as “Don’t eat cheese if you don’t want dementia”. But we need to look at the research and the real findings behind these headlines to understand how relevant they are to us.

现在媒体会将这些发现做成什么呢?我们可能会看到例如“如果你不想要痴呆,不要吃奶酪”这样的标题。但我们需要看看这些标题后面的研究和真正的发现,从而了解它们与我们的关系。


Here’s an example of some real newspaper headlines from a few years ago. Firstly, “Coffee – just the shot to fend off Alzheimer’s.” And “Caffeine addicts rejoice – a cup a day may keep Alzheimer’s at bay.” You might expect the research was conducted in a similar way to our hypothetical cheese study. A human prospective cohort study investigating the link between coffee consumption and the risk of developing Alzheimer’s Disease.

“咖啡 - 只是防止阿尔茨海默病的镜头”和“咖啡因成瘾者喜出望外 - 一天一杯可能会远离阿尔茨海默病”,这是几年前某些真正报纸头条的一个例子。首先,你可能希望以类似前面我们假设的奶酪研究的方式进行一项人类前瞻性队列研究来调查喝咖啡和发展阿尔茨海默病的风险之间的联系。


However, here’s the title of the article published by the researchers in the Journal of Neuroinflammation in 2008. “Caffeine blocks disruption of the blood brain barrier in a rabbit model of Alzheimer’s Disease”. The participants in this particular study were rabbits fed a high cholesterol diet.

然而,“咖啡因阻断阿尔茨海默病模型兔中血脑屏障的破坏”是研究人员在2008年神经炎症杂志发表的文章的题目。在该研究中的参与者是喂食高胆固醇饮食的兔子。


The researchers tested whether chronic ingestion of caffeine in their rabbits could protect them against changes in the blood brain barrier brought about by their high cholesterol diet. High cholesterol diets and high cholesterol levels, as well as disruptions in the blood brain barrier, have been associated with Alzheimer’s Disease, and also there have been studies suggesting that coffee consumption might be protective against Alzheimer’s Disease. So this is a reasonable research question.

研究人员检测了他们的兔子长期摄入咖啡因是否可以保护兔子们免受他们高胆固醇饮食带来的血脑屏障的改变。高胆固醇饮食和高胆固醇水平以及血脑屏障中的破坏已经被发现与阿尔茨海默病有关,并且还有研究表明咖啡消耗可能会防治阿尔茨海默氏病。所以这是一个合理的研究问题。


The researchers found that in their rabbits, caffeine consumption blocked the usual changes in the blood brain barrier brought about by their cholesterol-rich diet. And the researchers concluded that caffeine, and drugs similar to caffeine, might be effective in the treatment of Alzheimer’s Disease.

研究人员发现,咖啡因的消耗阻止了富含胆固醇的饮食通常带来的兔子的血脑屏障的改变。研究人员从而得出咖啡因和类似于咖啡因的药物可能会有效治疗阿尔茨海默病的结论。


Now it’s rather a long stretch to go from that research to suggesting that humans could fend off Alzheimer’s Disease by drinking more coffee.

目前从这项研究到建议人们可以通过喝更多的咖啡来抵御阿尔茨海默病还有相当长的距离。


The participants in the study were rabbits, not humans. They didn’t have Alzheimer’s Disease. They were fed a cholesterol-rich diet as a potential model for Alzheimer’s Disease. They didn’t drink coffee, they were given pure caffeine in their drinking water. Also, the researchers suggested that caffeine could potentially be used as a treatment for Alzheimer’s Disease, not as something that would prevent Alzheimer’s Disease.

研究中的参与者是兔子,而不是人。它们没有阿尔茨海默病。他们喂养了富含胆固醇的饮食作为阿尔茨海默病的潜在模型。它们没有喝咖啡,在它们的饮用水被添加了纯咖啡因。此外研究人员建议,咖啡因有可能用于治疗阿尔茨海默病,而不是预防阿尔茨海默病。


So be wary about making decisions based on media headlines. They may not accurately reflect the research that they’re based on. And also remember the difference between relative risk and absolute risk. A doubling in the relative risk of developing dementia might be something we should take notice of. But it may mean just a small increase in the absolute risk of developing dementia.

因此,基于媒体头条要谨慎地做出决策。他们可能无法准确反映他们所依据的研究。还要牢记相对风险和绝对风险之间的差异。发展为认知症的相对风险增加一倍或许是我们应该注意的事情。但它可能意味着发展为认知症的绝对风险的一个小小的增长。

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
2018-05-21
(10)认知症的遗传风险-Genetic risk for dementia

http://player.youku.com/embed/XMjY3ODMzMjY0OA



Dr Blochs

Blochs博士


Hello and welcome to the Wicking Dementia Laboratory, where one of the things we are working to understand is the genetics of dementia. When someone in their family has dementia, people are naturally concerned about whether it can be inherited. The genetics of dementia is complex and not fully understood. However, we do know that the vast majority of cases of dementia is not caused by an inherited genetic mutation. Dementia is so common that having several close relatives with dementia is not evidence of a genetic link.

您好,欢迎来到Wicking认知症实验室,我们正在此为搞清痴呆遗传学而工作。当他们的家族中有人患有认知症时,人们自然会关心是否这种疾病是否会遗传。痴呆遗传学是复杂的和未被充分了解的。然而我们知道绝大多数认知症的病例不是由遗传性基因突变引起的。认知症是如此常见,以至于有若干近亲患认知症不是遗传链接的证据。


There are a few gene mutations we know about that do cause dementia, however. So for a very small number of families, dementia can be inherited when the mutation is passed on. In these rare genetic forms of dementia, the onset is usually at a younger age, in the 40s or 50s.

但是据我们所知,有一些基因突变会导致认知症。因此对于非常少数的家族,当突变传递时,认知症可以被遗传。在这些罕见的认知症遗传形式中,人们通常会在40或50岁左右比较年轻的年龄发病。


Let’s meet one of those families. This is the Appleton family.

让我们会见其中的一个家庭。这是阿普尔顿家族。


This is Alan Appleton, and he has familial Alzheimer’s disease. He inherited a faulty gene that causes Alzheimer’s from his mother, who also had the disease.

这是阿兰·阿普尔顿,他有家族性阿尔茨海默病。他从他的母亲那里遗传了一个导致阿尔茨海默病的错误的基因,他的母亲也有这种疾病。


Three genes have been identified which, if mutated in certain ways, will cause familial Alzheimer’s disease. The mutation causing Alan’s Alzheimer’s is in a gene called APP.

已有三种基因被鉴定,如果它们以某些方式突变,将引起家族性阿尔茨海默病。导致Alan的阿尔茨海默症的突变存在称为APP的基因中。


We inherit half our genes from our mother and half from our father. While Alan inherited a faulty copy of the APP gene from his mother, he also inherited a normal copy from his father.

我们从自己的母亲继承了一半的基因,从自己的父亲继承了另一半的基因。虽然艾伦从他的母亲那里继承了一个有错误的APP基因拷贝,但他也继承了他父亲的正常基因拷贝。


This is Alice, Alan’s partner. Her mother also had Alzheimer’s disease, but it was the common sporadic type, so Alice has two normal copies of the APP gene.

这是爱丽丝,她是阿兰的配偶。她的母亲也有阿尔茨海默病,但它是常见的多发类型,所以爱丽丝有两个正常的APP基因拷贝。


Meet April and Augustus, Allan and Alice’s children. When someone carries a faulty gene that causes dementia, there is a 50-50 chance they will pass it on to their child, because they could pass on either their faulty or normal copy of the gene.

再来看艾伦和爱丽丝的孩子April和Augustus。当他们携带导致认知症的错误基因时,他们有一半的机会将它传递给他们的孩子,因为他们可以传递他们的错误或正常的基因拷贝。


April inherited the normal APP gene from her father and from her mother, so she will not get familial Alzheimer’s disease. She could still get sporadic Alzheimer’s disease, but she is at no greater risk than anyone else in the population.

April从她的父亲和母亲那里遗传了正常的APP基因拷贝,所以她不会得家族性阿尔茨海默病。她仍然可以患多发性的阿尔茨海默病,但她没有比人口中的任何人更大的风险。


Augustus on the other hand, inherited the faulty APP gene from his father and a normal gene from his mother. He will develop familial Alzheimer’s disease because the mutated gene is dominant over the normal copy.

在另一方面,奥古斯遗传了他父亲的错误APP基因拷贝和他母亲的正常基因拷贝。他将发展家族性阿尔茨海默病,因为突变基因拷贝比正常基因拷贝占优势。


Genetic forms of Alzheimer’s disease like the one affecting Alan and Augustus Appleton account for only around 1% of cases. So the vast majority of cases are sporadic, which means their cause is unknown. There are also other gene mutations that can cause other types of dementia, but for all the common causes of dementia, most cases are not inherited.

像艾伦和Augustus的这样的遗传性阿尔茨海默病,大约只占1%的病例。所以绝大多数情况是多发性的,这意味着他们的病因是未知的。还有其他可导致其他类型认知症的基因突变,但对于认知症的所有常见病因,大多数不是遗传性的。


So what about the sporadic forms of dementia, do genes play a role there? Research shows that, on average, people who have a close relative with a sporadic form of dementia have an increased risk of developing the condition, compared to someone without that family history. The increase in risk is similar to the increase we see for other risk factors like diabetes or smoking. And it is likely due to a combination of genetic and environmental influences on our risk of dementia.

那么对于多发性类型的认知症,基因是否在那里发挥作用呢?研究表明,平均来说,与没有家族史的人相比,具有患多发性认知症的近亲的人具有更高的发展该病症的风险。风险的增加类似于我们看到的像糖尿病或吸烟等其他风险因素导致的增加。这可能是由于遗传和环境共同影响我们患认知症的风险的缘故。


One of the genetic influences on our risk of Alzheimer’s disease is a gene called APOE. This gene comes in three normal variations. APOE3 is the most common variation, and doesn’t influence our risk of Alzheimer’s disease. APOE2 is associated with reduced risk, while APOE4 is known to increase the risk.

对我们患阿尔茨海默病的风险的遗传影响之一是称为APOE的基因。这个基因有三种常见的变异类型。 APOE3是最常见的变异,并不影响我们患阿尔茨海默病的风险。 APOE2与降低的风险相关,而APOE4已知会增加风险。


APOE4 does not cause Alzheimer’s, it only increases the risk of it developing. Some people with APOE4 never develop Alzheimer’s disease, and others who develop Alzheimer’s do not have APOE4. So even if someone has the APOE4 gene, it is impossible to predict whether or not they will develop dementia, but they are at increased risk.

APOE4不会引起阿尔茨海默症,它只会增加发展该病的风险。一些有APOE4基因的人从未发展成阿尔茨海默病,而发展成阿尔茨海默病的人没有APOE4。因此,即使有人拥有APOE4基因,也不可能预测他们是否会发展为认知症,但他们的患病风险有所增加。


In addition to APOE4, many other genes have been identified that have smaller effects on the risk of dementia. We are each born with an individual mix of genes, some of which may reduce our risk of dementia while others may increase it. At this time, it is not possible to measure any person’s individual genetic risk for dementia.

除了APOE4,许多其他基因已被确定对痴呆的风险有较小的影响。我们每个人都在出生时,带着各自的基因混合,其中一些基因可能会降低我们患认知症的风险,而其它的基因会增加风险。因此测量任何一个人的患认知症的个体遗传风险是不可能的。


Thanks for visiting the Wicking Dementia Laboratory and I hope you’ve enjoyed learning about the genetics of dementia.

感谢您访问Wicking认知症实验室,我希望您喜欢学习认知症的遗传学。

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
2018-05-21
(11)遗传和环境风险-Genetic and environmental risk

http://player.youku.com/embed/XMjY3ODMzMzA3Ng



Dr Blochs

Blochs博士


Hello. Today in the Wicking Dementia Laboratory we have 12 volunteers who are going to demonstrate the influence of modifiable factors on our risk of developing dementia. There are important non-modifiable risk factors for dementia; things we can’t change. We can’t stop growing older, which is the biggest risk factor for dementia. And we can’t change our family or our genes.

大家好。今天在Wicking认知症实验室,我们有12名志愿者将展示可修饰因素对我们发展认知症的风险的影响。有很多导致认知症的重要的不可修改的风险因素,这些是我们不能改变的。我们不能停止衰老,这是认知症最大的风险因素。另外我们不能改变我们的出身或我们的基因。


This is a group of 12 friends who have their own individual mix of genes inherited from their parents. Some of them will be at higher risk of developing dementia than others, because of their genes.

这组的12个朋友有自己特有的从他们的父母那里遗传的基因组合。他们的基因会使他们中的一些发生认知症的风险高于其他人。


We can’t actually measure anyone’s level of genetic risk because it’s complex and involves many different genes. But for the purposes of our demonstration, let’s line up our friends and assume this represents the order of their dementia risk according to the genetic make-up they were born with.

我们不能实际测量任何一个人的遗传风险水平,因为它是复杂的,并涉及许多不同的基因。但是为了方便我们的示范,让我们根据他们与生俱来的遗传修饰来假设这代表他们患认知症的风险高低,按照患病风险从高到低的顺序将我们的朋友排队。


Hypothetically, if genes were the only thing affecting their risk, let’s say 3 out of 4 people in the high risk group would get dementia. 2 out of 4 in the medium risk group would get dementia, and just 1 out of 4 in the low risk group would get dementia.

假设如果基因是他们患认知症风险的唯一的影响因素,那我们说,在高风险组中,每4个人中有3个会得认知症。在中等风险组中,每4个人中有2个会得认知症。而在低风险组中,只有四分之一的人会得到痴呆。


But genes are not the only factor that affects our risk. Now let’s look at some of the other factors that we know have an effect on our risk of developing dementia and see if anyone’s risk changes.

但是基因不是影响我们患病风险的唯一因素。现在让我们看看一些我们所知的对我们发展认知症的风险的其他影响因素,并看看是否有些人的风险会因此而改变。


Let’s start with Brenda, who hypothetically has the highest genetic risk. She eats a healthy diet including lots of vegetables and fruit and fish, which is most likely associated with a reduced risk of dementia, so she gets to move down the line, closer to a lower risk.

让我们从Brenda开始,假设她具有最高的遗传风险。她吃健康的食物,包括大量的蔬菜,水果和鱼,这很可能与痴呆风险降低相关,所以她向下移动到队列的后面,接近于低风险。


Chris uses aluminium pots and pans, but there is no evidence this affects dementia risk, so she stays where she is in the line.

克里斯喜欢使用铝锅和平底锅,但没有证据表明这影响痴呆的风险,所以她留在队列中她原来的位置。


Douglas does regular physical exercise, which is associated with a reduced risk of dementia, so he gets to move down the line, closer to a lower risk.

道格拉斯做常规体育锻炼,这与降低痴呆的风险相关,因此他向下移动到队列的后面,接近更低的风险。


Edmond smokes cigarettes, and we know smoking increases the risk of dementia, so he has a higher risk and unfortunately he moves up the line.

Edmond喜欢抽烟,我们知道吸烟会增加患认知症的风险,所以他有更高的风险,并且很不幸,他向上移动到队列的前面。


Fiona is 45 and has high blood pressure, but hasn’t had it checked or treated, and high blood pressure in midlife increases the risk of dementia, so she also moves up the line.

Fiona是45岁,有高血压,但没有检查或治疗过,高血压增加痴呆的风险,所以她也向上移动。



Gary has decided to eat coconut oil every day, but this hasn’t been proven to affect dementia risk, so he stays where he is.

加里已经决定每天吃椰子油,但这并没有被证明会影响患认知症的风险,所以他留在他原来的地方。


Heidi is learning a second language, and keeping your brain active is associated with lower dementia risk, so she gets to move down the line.

Heidi正在学习第二语言,因为保持大脑活跃与较低的患认知症的风险相关联,所以她向下移动。


Ivan meets regularly with his walking group and scrabble club. As social activity is associated with reduced dementia risk, he moves down the line.

Ivan定期与他的行走小组和拼字俱乐部成员会面。由于社会活动与减少的痴呆风险有关,他向下移动。


Joseph is 55 and very overweight, and we know that midlife obesity is associated with increased dementia risk, so he moves up the line toward higher risk.

约瑟55岁,体重超重,我们知道中年肥胖与患认知症的风险增加相关,因此他向上攀升到更高的风险。


Katie has diabetes and Luigi has depression. Both can be associated with increased dementia risk if poorly managed, so they move up the line toward higher risk.

Katie有糖尿病,Luigi有抑郁症。如果管理不善,两者都可能与增加的患认知症的风险相关,因此他们向上移动到具有更高风险的位置。


Mary has decided to take ginkgo biloba supplements, but there is no evidence they can reduce dementia risk, so she stays where she is.

玛丽决定服用银杏叶补充剂,但没有证据表明它们可以减少患认知症的风险,所以她留在她原来的地方。


Our friends have demonstrated how environmental and medical factors can modify our risk of dementia.

我们的朋友们已经展示了环境和医学因素可以如何改变我们患认知症的风险。


Douglas started in the high risk group, but thanks to regular physical activity, he moved to the medium risk group.

道格拉斯开始在高风险组,但由于定期体力活动,他移动到中等风险组。


Fiona, who has high blood pressure and doesn’t have regular check-ups to keep it controlled, started with a medium risk but moved into the high risk group.

Fiona,有高血压,他没有定期检查以保持控制,开始在中等风险组,但后来转移到高风险组。


Heidi and Ivan moved to the low risk group by keeping their brains active with mental and social activities.

Heidi和Ivan通过参与精神和社会活动来保持他们的大脑活跃性,从而转移到低风险组。


This shows the choices we make can influence our risk of dementia just as much as our genetics. Of course, it’s not as simple as our example here, because we each have many different lifestyle and health factors that might be increasing or decreasing our risk.

这表明我们做出的选择是可以影响我们患的认知症的风险,这和我们的遗传对我们的影响大小是一样。当然,这不像我们这里举的例子那么简单,因为我们每个人都有很多不同的生活方式和健康因素,这些都可能会增加或降低我们的风险。


The best any of us can do to reduce our risk of dementia is live a healthy and active life, and manage vascular risk factors and depression. This can’t guarantee we won’t get dementia, but we’d all prefer to be in the low risk group than the high risk group.

我们任何人都可以做的减少患认知症的风险的最好方法是过健康和积极的生活,管理血管风险因素和抑郁症。这不能保证我们不会得认知症,但我们所有的人都喜欢在低风险组而不是高风险组。


Thanks everyone. Who’s for some fun brain stimulation?

Let’s build something!

感谢大家。谁在为了大家提供一些有趣的东西来刺激大脑?

让我们建立一些什么!


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
2018-05-21