公开课-关爱惟士
公开课
(6)什么是认知症-What is Dementia?

课程视频:http://player.youku.com/embed/XMjY3ODI5MTU0OA



什么是认知症?


Prof. James Vickers

James Vickers教授


Dementia is a term that we use to refer to a change in functioning from previous levels. The domains that are affected by dementia include your higher cognitive abilities, personality and behaviour. There are many dozens of diseases that will actually cause dementia, and most of these are associated with advanced ageing, although some, particularly with a high genetic predisposition, can occur at much younger ages.

认知症是一个我们用来指从以前的脑功能水平发生改变的术语。受认知症影响的范畴包括你更高的认知能力,个性和行为。尽管某些疾病,特别是具有高遗传倾向的疾病,可以在更年轻的年龄发生,但实际上,有许多疾病会导致认知,并且这些疾病中的大多数与晚期衰老有关。


The four major neurodegenerative diseases that cause dementia are Alzheimer’s Disease, Lewy Body Disease, Frontotemporal Dementia and Vascular Dementia. And sometimes these occur singularly and they can also occur in combination. And it’s these four that we’ll focus on in the presentation today.

引起认知症的四种主要的神经退行性疾病是阿尔茨海默病,路易体疾病,额颞叶痴呆症和血管性痴呆。这些疾病有时单独发生,也可以组合发生。我们将在今天的演讲中重点介绍这四种疾病。


The major cause of dementia is Alzheimer’s Disease, and this probably accounts for around 50% to 60% of cases. We know that Alzheimer’s Disease is characterised by specific pathological changes that occur inside the brain, and these were originally described by Alois Alzheimer at the beginning of the 20th century. The three changes include those that happen at the macroscopic level, which involves shrinkage or atrophy of the brain, and this can affect particular structures of the cerebral cortex, including the frontal lobe, temporal lobe and parietal lobe. The other two pathological changes occur at the microscopic level, and these are neurofibrillary tangles and amyloid plaques. Amyloid plaques are spherical structures that occur between nerve cells and are comprised of a protein known as A-beta. Now A-beta is a normal protein that you would find in all of our brains, but in Alzheimer’s Disease, it undergoes an abnormal transformation. It forms small fibrils that accumulate together to form plaques, and where plaques form in the brain, they cause damage to nerve cells, particularly the processes of nerve cells, the axons, the dendrites, as well as synaptic connections between those nerve cells. The other major microscopic change that occurs inside the brains of people with Alzheimer’s Disease is the neurofibrillary tangle. Now, within all nerve cells there’s a fine meshwork of filamentous proteins that we refer to as the cytoskeleton. When a nerve cell is affected by Alzheimer’s Disease, this cytoskeleton collapses and is replaced by the neurofibrillary tangle. The main protein that comprises this tangle is an altered form of a normal brain protein we refer to as tau. Now, tangles probably take many years to actually develop within nerve cells, and they seem to follow the initial development of plaques within the brain. They are also very insoluble structures, which means they don’t dissolve very easily. So when a nerve cell dies, usually the tangle is left behind, and we refer to this as a tombstone or ghost tangle. There are new imaging technologies that are being developed for Alzheimer’s Disease that might help us visualise these amyloid plaques and neurofibrillary tangles inside the brains of people while they’re alive. If we combine the data from these new studies with that which has been derived from pathological studies, we now appreciate that there’s a particular sequence of pathological change that occurs inside the brain with Alzheimer’s Disease. It seems likely then that plaques may occur many years, sometimes as many as ten to fifteen years, before you develop overt symptomatology. The plaques appear to precede the neurofibrillary tangles and the neurofibrillary tangles themselves are more closely linked with the loss of synaptic connections between nerve cells, which lead to the pattern of symptoms. In this regard, Alzheimer’s Disease is a degenerative and progressive disorder in that the disease develops from one stage to the next - from a clinical silent period, where plaques develop inside the brain, through to the initial stages of the disease, which can be insidious and often difficult to detect, then through to the progressive deterioration in higher cognitive functions. One of the early cognitive functions that seems to be affected by Alzheimer’s Disease is short-term memory and the ability to form new memories.

导致认知的主要原因是阿尔茨海默病,可能约占50%至60%的病例。我们知道,阿尔茨海默病的特征是在脑内发生特定的病理性变化,这些特征最初在20世纪初由Alois Alzheimer所描述。这三种变化包括在宏观水平发生的改变,其涉及脑的收缩或萎缩,并且影响包括额叶,颞叶和顶叶在内的大脑皮质的特定结构。其他两种病理性改变发生在微观水平,它们是神经原纤维缠结和淀粉样斑块。淀粉样的蛋白斑块是存在于神经细胞之间的球形结构,并由称为A-beta的蛋白质所构成。在我们所有正常的大脑中,A-beta是一种正常的蛋白质。但在阿尔茨海默病患者的大脑中,这种蛋白发生异常的转变。它形成小的原纤维,进而这些原纤维聚集在一起形成斑块,并且这些在脑中形成的斑块对神经细胞,特别是神经轴突和树突以及这些神经细胞之间的突触连接造成损害。在阿尔茨海默病患者脑内发生的另外一个主要的微观变化是神经原纤维缠结。在所有的神经细胞中都有一个由丝状蛋白构成的细丝网络,我们目前称之为细胞骨架。当神经细胞受阿尔茨海默症影响时,该细胞骨架塌陷并被神经原纤维缠结所替代。构成该缠结的主要蛋白质是一种正常脑蛋白的改变形式,我们称为tau蛋白。缠结可能需要许多年才真正在神经细胞内发展,并且它们似乎在脑内的最初的斑块的发展之后形成。它们也是非常不溶的结构,这意味着它们非常不易溶解。因此,当神经细胞死亡时,通常会留下缠结,我们将其称为墓碑或幽灵缠结。有一些为阿尔茨海默病而正在开发的新的成像技术,可能会帮助我们活体观察人类大脑内的这些淀粉样斑块和神经原纤维缠结。如果我们将来自这些新研究的数据与来自病理学研究的数据相结合,现在我们会认识到在阿尔茨海默氏病患者的脑内发生了特定的病理变化序列。斑块似看起来似乎在症状出现之前已经存在了许多年,有时多达十至十五年。斑块似乎出现在神经原纤维缠结之前,并且神经原纤维缠结本身与神经细胞之间的突触连接的丧失更紧密地相关,从而导致症状的产生。在这方面,阿尔茨海默病是一种退行性和进行性疾病,其中疾病从一个阶段发展到下一个阶段 - 从斑块在脑内发展的临床沉默期,直到疾病发生的初始阶段,这个过程可能是隐蔽的并且经常难以检测的,然后进入更高的认知功能逐渐恶化时期。似乎受阿尔茨海默病影响的早期认知功能之一是短期记忆和形成新的记忆的能力。


In Alzheimer’s Disease, we know that particular brain regions are vulnerable to degeneration, and even within those brain regions, certain nerve cells are particularly susceptible. One of the structures of the brain that’s affected early in the disease is the medial temporal lobe, and as this degenerates, you may see some symptoms, such as an inability to form new memories and difficulties generally in short-term memory. But then the disease progresses to other brain regions, to other lobes of the cerebral cortex, and as this occurs you will see difficulties in other higher cognitive areas, as well as behaviour and personality, and this might include planning ability, logical thinking, orientation in space and time, as well as language.

在阿尔茨海默病中,我们知道特定的脑区易于退化,甚至在那些脑区内,某些神经细胞也特别易感。在疾病早期受影响的脑的结构之一是内侧颞叶,并且随着这种退化,您可能会看到一些症状,例如通常在短期记忆中不能形成新的记忆和困难。但随后疾病进展到其他大脑区域,到大脑皮质的其他叶区,并且这种情况下,你会看到在其他更高的认知领域,以及行为和个性方面的困难,这可能包括规划能力,逻辑思维能力,在空间和时间的方向感,以及语言能力。


The speed of progression, as well as the age of onset, of Alzheimer’s Disease does vary between individuals. We don’t really understand why this is the case, but it’s likely mainly due to genetic predisposition, but other lifestyle factors may well play a role.

阿尔茨海默氏病的进展速度以及发病年龄在个体之间存在差异。我们不太明白为什么会是这样,但它可能主要归因于遗传倾向,但其他生活方式因素也可能发挥作用。


In Alzheimer’s Disease, there are likely to be a range of genetic risk factors that contribute to your relative risk of developing this condition. The best known one, and the one that has the most impact on your risk, is the apolipoprotein E gene. Now, this comes in three variations – Epsilon II, Epsilon III and Epsilon IV. You inherit one version of this gene from each of your parents. Essentially, the more of the Epsilon IV version of this gene you have, the higher risk you have of developing dementia as you get older. In less than 5% of cases, there’s a much stronger genetic predisposition and we often refer to this as familial forms of Alzheimer’s Disease. We know of three genes that carry a range of mutations that can cause familial Alzheimer’s Disease. One of these is the amyloid precursor protein gene, and we know that this is then linked potentially to the production of amyloid beta that forms the plaques in Alzheimer’s Disease.

在阿尔茨海默病中,可能存在一系列遗传风险因素,这些因素会促进您发展这种疾病的相对风险。最著名的一个,对你的风险影响最大的是载脂蛋白E基因。现在,这有三种基因变异 -  Epsilon II,Epsilon III和Epsilon IV。你每个人从各自的父母继承这个基因的一个版本。基本上,你如果拥有更多的Epsilon IV版本的基因, 等你变老时你就有更高的发展为老年认知症的风险。在不到5%的病例中,有更强的遗传倾向,我们经常将其称为家族型阿尔茨海默病。我们知道三个携带一系列可导致家族性阿尔茨海默病的突变的基因。其中之一是淀粉样蛋白前体蛋白基因,并且我们知道这可能与在阿尔茨海默病中形成斑块的淀粉样蛋白β的产生有关。


Another cause of dementia is Lewy Body Disease. Now, this is known by a variety of terms, including diffuse Lewy Body Disease, Dementia of the Lewy Body Type and Alzheimer’s Disease with Lewy Bodies. The cardinal pathological feature of Lewy Body Disease is the presence of an abnormal proteinaceous inclusion inside nerve cells called the Lewy Body. Now, the Lewy Body is a spherical structure made up of proteins, fine filaments and lipids. It also occurs as the main pathological feature of Parkinson’s Disease, and we think that Parkinson’s Disease and Lewy Body Disease are related to each other. Some of the clinical features of Lewy Body Disease may well include motor problems that you see in Parkinson’s Disease, such as tremor. Similarly, if you have Parkinson’s Disease for a long period of time, you may then develop cognitive issues that are very similar to what we see in Lewy Body Disease. Inside the brains of people with Lewy Body Disease, you’ll often also see amyloid plaques, and this probably speaks to some kind of interrelationship between Lewy Body Disease and also Alzheimer’s Disease.

认知症的另一原因是路易体病。现在,这种疾病以弥漫性路易体病,路易体型的认知和路易体的阿尔茨海默病各种术语命名。路易体病的主要病理特征是名为路易体的存在于神经细胞内的异常蛋白质内含物。目前的研究表明,路易体是由蛋白质,细丝和脂质组成的球形结构。它也是帕金森病的主要病理特征,我们认为帕金森病和路易体病彼此相关。路易体病的一些临床特征可能包括您在帕金森病中看到的运动问题,例如震颤。同样,如果你有长期的帕金森病,你可能会发展出与我们在路易体病中看到的非常相似的认知问题。在路易体病的人的大脑中,你经常也会看到淀粉样斑块,这可能是路易体病和阿尔茨海默病之间的某种关联。


Another cause of dementia is Frontotemporal Dementia, and this is really a spectrum of different diseases. Broadly, they’re characterised by dramatic shrinkage, or atrophy, of brain regions, such as the frontal lobe, and the frontal sections of the temporal lobe. The symptomatology of the disease broadly follows the damage to these cortical areas – for example, with frontal lobe damage, comes changes in personality and behaviour, as well as higher cognitive skills, such as planning and judgement. With damage to the temporal lobe, there’s often problems with language and speech production.

认知症的另一个原因是额颞叶痴呆,这其实是一系列不同的疾病。广泛地讲,它们的特征是脑部的急剧收缩或萎缩,例如额叶和颞叶的正面部分。疾病的症状学大致广泛存在于对这些皮质区域的损伤 - 例如,伴随额叶损伤,发生个性和行为上的变化,以及更高的认知技能,例如规划和判断能力。由于颞叶损伤,语言的产生常常出现问题。


Of all of the conditions that cause dementia, frontotemporal dementia probably has the strongest genetic predisposition. So around about 30% to 40% of cases of frontotemporal dementia are likely linked to particular genetic mutations. And because of this genetic predisposition, these cases tend to have a relatively early onset.

在所有引起认知症的条件中,额颞叶痴呆可能具有最强的遗传倾向。因此,大约30%至40%的额颞叶痴呆病例可能与特定的遗传突变相关。由于这种遗传倾向,这些病例往往发病相对较早。


Vascular dementia is sometimes known as multi-infarct dementia, and this involves an interruption to the normal blood flow into the brain. In most cases of vascular dementia, this involves damage and disruption to the small blood vessels that penetrate through the brain, particularly in the white matter tracks underlying the cerebral cortex. In other cases of vascular dementia, there might be a series of small strokes occurring in different regions of the brain. Vascular pathology is actually quite common with advanced ageing and this vascular disease can coexist with other forms of dementia, such as Alzheimer’s Disease.

血管性痴呆有时被称为多梗塞性痴呆,并且这涉及到进入脑的正常血液流动的中断。在大多数血管性痴呆的病例中,这涉及对穿透大脑的小血管的损伤和破坏,特别是在大脑皮质下面的白质轨迹中。在血管性痴呆的病例中,可能在脑的不同区域中发生一系列小的中风。血管病理学实际上与晚期老化相当常见,并且这种血管疾病可以与其他形式的认知共存,例如阿尔茨海默氏病。


These different forms of dementia are the focus of intense study globally. We are trying to understand the sequence of pathological changes that lead to dementia. In many cases, this is probably largely attributed to advanced ageing, as well as your genetic predisposition, but we’re also interested in how more modifiable risk factors may play out in terms of the disease pathology. Ultimately, we’re interested in therapeutic agents that might modify disease progression, so might have an effect on the specific pathological hallmarks, or it might be that we can look at interventions that might improve on your relative resilience to these dementing disorders.

这些不同形式的认知是全球密集研究的焦点。我们试图理解导致认知的病理变化的顺序。在很多情况下,这可能主要归因于晚期老龄化以及您的遗传倾向,但我们还感兴趣的是如何更多可纠正的疾病病理学方面的风险因素。最终,我们对可能改变疾病进程的治疗试剂感兴趣,因此可能对具体的病理特征产生影响,或者我们可以看到可能改善对这些认知病症的相对弹性的干预。


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
(7)认知症对全球的巨大影响-The Global impact of dementia

课程视频:http://player.youku.com/embed/XMzYwNzE3NTcyMA



Professor 

Perminder Sachdev

Perminder Sachdev教授


We can look at figures from perhaps two sources here. One is of course the global observatory in London, which was set up by the ADI some years ago. That observatory, run by Professor Martin Prince, has been collecting data, and these data were actually published by the Alzheimer's Disease International in 2015. The estimate was that there were roughly about 45 to 50 million people, I think the figure they came to was 47.8 or something like that, around the world. More recently there was another publication that’s from the Global Burden of Disease group, which is run from Washington DC. They came to very similar figure, about 45 million, so that’s really the number of people overall in the world, with a diagnosis of dementia.

我们也许可以从两个地方查找全球认知症患者的数据。其中一个当然是伦敦的全球天文台,它是由ADI在多年前建立的。Martin Prince教授一直在用这个天文台收集数据,而这些数据于2015年刊登在了国际阿尔兹海默病期刊上。该数据估计全球有4.5-5千万人被诊断为认知,我认为他们得到的数据应该大约在4.78千万左右。最近,另一份来自华盛顿的全球疾病负担小组的出版物也指出全球有4.5千万人被诊断为认知症。这个数据和之前Martin Price教授他们采集的数据(4.5-5千万)非常接近。所以,全球真的有这么多认知症患者。


But I must emphasise that this is not a precise figure, and for various reasons. One is that the data we have from many countries, is secondary data, we do not have good surveys. Even from high income countries or developed countries, the figures on dementia vary depending upon what criteria have been used, what the sampling strategy has been. This is a very rough guide.

但是,因为种种原因,我必须要强调的是这并不是一个准确的数据。第一,我们从很多国家获取的数据都是二手数据,我们并没有做好的调查。即便从高收入或者发达国家获得的有关认知症患者的数据也取决于我们用了什么样的标准以及采样方法。这是一个非常粗略的数据。


I think there are two points I want to make here. First point is that there is an increase in the number of people, and that is quite a rapid increase projected over the next 30 to 40 years. Primarily that increase is driven by the increase in the total number of people, who are over the age of 60 or 65. We know that dementia increases exponentially with age, and especially after the age of 65, there is a doubling of the number of people with dementia. Every 6 years or 6.3 years to be precise, I think is probably the estimate. The more older people there are, the more people with dementia there will be. We know there are going to be more and more older people around the world.

我认为这里有两点我要指出。第一点就是认知症患者人数在增长,而且在未来的30-40年,预计还会有相当快速的增长。这种增长主要是由于年龄超过60或65岁的人口总数量的增长导致的。我们都知道认知症的发病率随着年龄的增长呈指数型增长,特别是在65岁以后,认知症患者的数量增加了一倍。准确地讲,是每6年或每6.3年增加一倍,我认为这也许是预估。老年人越多,认知症患者越多。我们知道全球将会有越来越多的老年人。


In particular in the developing countries or low income countries and low and middle income countries, there is going to be a rapid increase, because those populations are ageing now. Whereas in the high income countries, the population has already aged to a significant degree. But ageing is happening very quickly in those countries. In fact they're going to contribute more and more towards people with dementia in the future. That’s really one reason that there is going to be more and more people with dementia around the world. It's projected that by the middle of the century, the number is going to be more than twice as many. One projection is maybe about 150 million people by the middle of the century around the world.

特别是在发展中国家或低收入以及中低收入国家,认知症患者将会有一个快速的增长,因为这些国家的人口正在老龄化。而在高收入国家,人口老龄化已经到一个相当大的程度了。但在这些国家,人口老龄化正在加速。实际上,他们将对未来认知症患者的增加做出越来越大的贡献。这确实也是全球越来越多认知症患者的原因之一。据估计,在本世纪中叶,认知症患者数将是这个数据的两倍不止。另一个预测是,到2050年,全球也许会有1.5亿认知症患者。


The second point I want to make is that there are some other trends we are seeing. Especially this trend has come from developed countries, high income countries, that in fact the incidence of dementia may actually not be rising, may in fact be falling. I think here we need to distinguish between the overall numbers, the prevalence of dementia, and incidence. By incidence we mean people with a new diagnosis of dementia, so how many new people are coming in to this fold of getting a diagnosis of dementia. There have been some studies from Europe and from North America, which have suggested that in fact the incidence of dementia in the developed countries may be falling, or may have been falling for the last two decades or so, and may continue to fall for some more time. Although we think that that will plateau, sometime in the future.

我想说的第二点是,我们看到了一些其他的趋势。特别来自发达国家或高收入国家的趋势——事实上,认知症的发病率并没有增加,也许实际上正在下降。我认为在这里我们需要区别认知症总人口、患病率和发病率。发病率指的是新诊断出为认知症的患者,也就是说有多少人刚加入被诊断为认知症的行列。欧洲和北美已经有一些研究表明实际上在发达国家认知症的发病率也许在降低或可能在过去的20年中一直在下降,并且有可能会持续下降一段时间。尽管我们认为这可能在未来的某段时间趋于平稳。


In particular I want to highlight three studies here. The first study perhaps, is from the UK, which is called the MRC CFAS study. Essentially it was a large study from six centres in the United Kingdom, which was done twice. Once this study was done to look at the overall prevalence of dementia in the UK in the early ‘90s. Then the study was repeated 20 years later, so to see after a generation what has happened. The short message from that study is that what they had projected was that the rate would be about 8.1% 20 years later. But actually the rate that they found on this survey, on this, was much lower, about 6.7%. There were fewer people with dementia than they had projected from the earlier estimates. In fact the total number had not gone up very much, even though the number of people who were at risk, of that old age population, had gone up significantly, suggesting that fewer people were developing dementia than 20 years earlier.

我在这里要特别强调三项研究。第一项来自英国的MRC CFAS研究,它是由6个中心做的大型研究,这项研究已经被做了2次。最初这项研究是为了调查英国90年代早期认知症的患病率。然后,这项研究在20年后重新做了一次,以此来看过了一代人后发生了什么。这项研究预测的是在20年后认知症的患病率大约是8.1%,然而,实际上通过他们的调查,他们发现这个数据更低,大约是6.7%。认知症患者比他们之前估计的要少。实际上,尽管认知症高危老年人口数量显著增加了,认知症总人数并没有增加很多。这说明与20年前相比,认知症的患者更少了。


Then there’s another study from The Netherlands, that's the Rotterdam study, and the Rotterdam study is interesting because they've been following people in Rotterdam as they grow older over several years now. They looked at their rates of dementia and here they're looking at new cases, which is the incidence of dementia, 10 years apart. They found that 10 years later, the incidence was lower. Although not significantly lower, but slightly lower, not statistically significant. But a very interesting study that’s been published from the United States and that’s from a place called Framingham in Massachusetts. The audience will be familiar with the Framingham study, which actually is a study of cardiovascular health, which has been going on now for 40 to 50 years.

然后还有一项来自荷兰的鹿特丹研究,这项研究很有趣,因为他们跟踪了鹿特丹市民很多年,陪着他们慢慢变老。他们调查鹿特丹市民的认知症患病率和10年后新增加的认知症患者数量,也就是认知症的发病率。他们发现10年后,认知症的发病率更低。尽管并没有显著地降低,只轻微降低了一点点,不具有统计学意义。但是,还有一项已经在美国马萨诸塞州的弗雷明汉发表的研究。大家以后将会熟悉弗雷明汉研究,这实际上是一项关于心血管健康的研究,它已经持续了40-50年。


They started with heart health and now they've gone on to brain health. They've been looking at dementia cases now for about 40 years. They looked at rates in the late ‘70s, and then the ‘80s, ‘90s and the 2000s and see what has happened. They found that each decade, the incidence of dementia has actually gone down, to the extent that over this period of 30 years, there was about a 44% reduction in the incidence or new cases of dementia. So in fact there's both a bad news story and a good news story in this. The bad news story is that overall the number of people with dementia around the world is increasing and is likely to increase. The greatest increase is going to be in low and middle income countries. But high income countries, still there's going to be maybe an increase, but not as much as we had feared in the past. Because there is probably a levelling off or even a slight decline in these people. Unfortunately in the low and middle income countries, this decline is not likely to happen very soon, in fact at this point, there is some suggestion that the rates may be increasing to some extent because of certain risk factors.

他们起初是研究心脏健康的,现在,他们研究大脑健康。到现在为止,他们已经研究了认知症病例将近40年。他们调查了70年代末、80年代、90年代和21世纪以来认知症患者的患病率并且研究发生了什么。他们发现每10年,认知症的发病率实际上已经下降了,在这30年期间,认知症的发病率和新发病例已经减少了大概44%。因此,事实上,这里面既有坏消息,也有好消息。坏消息就是全球认知症患者的总数量正在增加而且有可能增加。中低收入国家增长最多。但是,高收入国家仍然可能会有增长,但不会像我们过去所担心的增长那么多。因为有可能这个数据会趋于平稳或者轻微的下降。不幸的是,在中低收入国家,这种下降不太可能很快发生,事实上,在这一点上,有一些迹象表明,因为某些风险因素,认知症发病率可能会在一定程度上增加。


We do not know for sure why the numbers in low and middle income countries are increasing. But definitely the major increase is because there are more older people, the life span is increasing so more people are at risk of developing dementia. So that’s the big bulk. But whether there is another contribution being made by factors such as obesity, diabetes, poor metabolic health, cardiovascular disease, stroke, we’re not sure. Because some of these are increasing, unfortunately in many low and middle income countries, with changes with industrialisation, changes in dietary patterns, changes in physical activity levels. Rates of diabetes are increasing, rates of stroke are increasing. This is happening in India, in China, which are major populations really in terms of total world population. It is possible that this will flow on through in terms of rates of dementia in the future. At this point we do not know, but that’s something that we have to watch out for.

我们不是很清楚为什么在中低收入国家,认知症患者数量在增加。但是,能肯定的是,这些患者主要的增长是因为人口老龄化,人们的寿命越来越长,所以更多的人存在患认知症的风险。因此,这是很大的一个原因。但是,我们也不确定是否有其他导致认知症的风险因素,比如说肥胖、糖尿病、代谢不良、心血管疾病或者中风等。因为,不幸的是,在中低收入国家,随着工业化、膳食结构以及体育锻炼水平的变化,一些上述风险因素在增加。在印度和中国这种全球人口大国,人们糖尿病和中风患病率都在增加。我们不知道这是否有可能在未来增加认知症的患病率,但是这是我们必须注意的事情。


Studies that have looked at the changes in prevalence and incidence of dementia across say a 20 year span or over a generation, have tried to hone in to the possible reasons. If you look at the Framingham study, they found that the major change was in vascular dementia, not in Alzheimer's disease, so it is suspected that it could be vascular risk factors, such as better control of hypertension, better control of diabetes, good management of cardiovascular disease. But that did not explain all of the change really.

那些研究了认知症患病率和发病率20年或者超过一代人的研究试图找到可能的原因。如果你去看弗雷明汉研究,他们发现主要的变化是血管性认知,而不是阿尔兹海默病。因此,它怀疑可能是血管风险因素,比如更好地控制好血压、糖尿病以及心血管疾病。但是这并不能真的解释所有的变化。


There is a suspicion that it may be other factors, and starting off with early life factors, such as good education. We find that getting a good education early in life, sets you up for a good health lifestyle, throughout your life. It also gives you protection in terms of cognitive ageing, of decline in your cognitive function as you age. This is evidence that comes from the European studies as well and in fact even from our own study in Sydney. Early education is a significant protective factor. It may work through various different ways. But certainly better control of vascular risk factors, good diet through life, management of obesity, physical activity through life, are all important and maybe all are playing a role in this, in terms of the improvements we are seeing.

有人怀疑可能是其他风险因素,比如说像良好的教育这样的早年生活因素。我们发现,在人生的早期接受良好的教育会让你在一生中拥有好的健康的生活方式。它也能在对老龄化认知方面给予你保护,大家都知道,你的认知功能会随着年龄的增长而下降。来自欧洲的多项研究,甚至是我们自己在悉尼做的研究都证实这一点。早期教育是一个重要的保护因素。它可以通过各种不同的方式影响你。但是当然在整个生命的过程中更好地控制血管风险因素,良好的饮食习惯,肥胖的管理以及体育锻炼都很重要,也许这些所有的因素都对我们看到的认知症患病率的改善发挥了作用。


I think I should add then, that we suspect that if we are seeing an improvement in the high income countries, in the last two to three decades, we cannot take it for granted. Because it’s very likely that this will level off and then we are also seeing that in our younger populations, in developed countries, rates of obesity are increasing, and poor diet, dietary patterns are increasing as well. It’s possible that we might reverse some of these gains in the future. We cannot actually sit back on our laurels, we have to be vigilant forever.

我想我应该补充一点,我们猜想即使我们在高收入国家看到的认知症患病率在过去的20到30年间有所改善,我们不能想当然地认为这是理所当然的。因为很有可能这种现状会趋于平稳,然后我们也看到在发达国家,我们年轻的一代人中,肥胖率、不良饮食、膳食结构这些风险因素都在增长。未来这些改进有可能被我们扭转。我们不能坐以待毙,我们必须时刻保持警惕。


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
(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