Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study.
Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study.
复制标题
痴呆症的流行病学病理：医学研究委员会认知功能和衰老研究中死亡的可归因风险。
DOI：
10.1371/journal.pmed.1000180
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发表时间：
2009-11
期刊：
影响因子：
15.8
通讯作者：
Ince P
中科院分区：
文献类型：
--
作者：
Matthews FE;Brayne C;Lowe J;McKeith I;Wharton SB;Ince P
来自医学研究委员会认知功能和衰老神经病理学研究的研究人员对英国一组同意捐献大脑的老年人进行了一项分析，分析了导致痴呆症的脑部病理。痴呆症药物的开发旨在调节引起临床综合征的病理过程。人口数据（流行病学神经病理学）将有助于建模和预测此类疗法对老年人痴呆负担的潜在影响。目前，这只能通过验尸结果来探索。我们在MRC认知功能和衰老研究（MRC CFAS）中报告了常见的与年龄相关的退行性疾病和血管病变以及其他因素导致死亡时痴呆的归因风险（ARs）。一项针对英国老年人的多中心、前瞻性、纵向研究与脑捐赠计划有关。456例连续脑捐献的神经病理学评估退行性和血管病变。采用Logistic回归模型，结合自启动分析和敏感性分析，估计因特定病理和其他因素导致的痴呆死亡时的AR。MRC CFAS中导致痴呆死亡时发生AR的主要因素是年龄（18%）、小脑（12%）、新皮质神经性斑块（8%）和神经原纤维缠结（11%）、小血管疾病（12%）、多血管病变（9%）和海马萎缩（10%）。其他重要因素包括脑淀粉样血管病（7%）和路易小体（3%）。这种AR估计不能从生活人口中得出；相反，他们估计了特定病理对死亡时痴呆的相对贡献。我们发现，多种病理决定了痴呆症的总体负担。当痴呆症相对“纯粹”时，针对特定病理的治疗可能会产生深远的影响，但对于大多数混合性疾病和人口而言，可能就不那么令人印象深刻了。这些数据证明了一系列策略和联合治疗，以对抗认知能力下降和痴呆的退行性和血管决定因素。丢失个人物品和忘记别人的名字通常是衰老的正常现象。但健忘的增加也可能是痴呆症的征兆，痴呆症是由几种影响大脑结构的疾病引起的一组症状。痴呆症最常见的形式是阿尔茨海默病。在这种情况下，被称为斑块的蛋白质团块和神经原纤维缠结在大脑中形成并导致其退化。血管性痴呆也很常见，因为血液循环问题导致大脑部分缺氧。痴呆症患者有两种或两种以上的“认知”功能问题——思考、语言、记忆、理解和判断。随着病情的发展，他们逐渐失去处理正常日常活动的能力，直到他们需要全面护理，他们的个性经常改变，他们可能变得烦躁或具有攻击性。痴呆症在65岁之前很少见，但大约四分之一的85岁以上的人患有痴呆症。随着高龄老人的增加，痴呆症患者的数量也在增加。根据最新估计，目前约有3500万人患有痴呆症，到2050年，可能有1.15亿人患有这种疾病。目前还没有治愈痴呆症的方法，但正在开发许多旨在调节大脑中可能导致痴呆症症状的特定异常（病理）变化的药物。为了评估这些潜在昂贵的新疗法可能产生的影响，专家们需要知道每种类型的脑部病理与痴呆相关的比例。虽然一些大脑变化可以通过计算机断层扫描等技术在活体大脑中检测到，但大多数大脑变化只能在人死后的大脑中进行研究（死后大脑）。在这项研究中，作为英国医学研究委员会认知功能和衰老研究（MRC CFAS）的一部分，研究人员寻找老年人痴呆与其死后大脑病理变化之间的联系，并估计与大脑特定病理特征相关的死亡时痴呆的归因风险（AR）。也就是说，他们估计了直接归因于每种病理类型的痴呆的比例。近20年前，MRC CFAS在英格兰和威尔士的六个地点采访了超过18000名65岁或以上的人，以确定他们的认知功能和处理日常活动的能力。20%的参与者，包括有和没有认知障碍的人，随后被更详细地评估，并被邀请捐献他们的大脑进行尸检。截至2004年，已有456人捐献了他们的大脑。这些捐赠者的痴呆状态是根据他们的评估访谈和死亡证明以及与亲属和护理人员的访谈数据确定的，并仔细检查他们的大脑是否有异常变化。然后，研究人员使用统计方法来估计与各种异常大脑变化相关的死亡痴呆的AR。导致死亡时痴呆的主要因素包括年龄（18%的死亡时痴呆可归因于这一因素）、斑块（8%）和大脑新皮质区域的神经原纤维缠结（11%）、小血管疾病（12%）和血管的多种异常改变（9%）。这些发现表明，多种大脑异常变化决定了痴呆症的总体负担。重要的是，他们还表明痴呆症通常与混合病理变化有关——许多痴呆症患者的大脑变化与阿尔茨海默病和血管性痴呆相一致。由于痴呆症患者的寿命长短不等，在此期间，他们大脑中的异常变化可能会发生变化，因此很难将这些发现推断到生活在老年人群中。此外，只有一小部分MRC CFAS参与者捐献了他们的大脑，所以这项研究的结果可能不适用于一般人群。然而，这些发现表明，目前正在开发的新疗法可能对减轻痴呆症的总体负担作用不大，因为大多数人的痴呆症涉及多种病理。因此，可能有必要制定一系列策略和联合疗法来应对正在流行的痴呆症。请通过本摘要的在线版本http://dx.doi.org/10.1371/journal.pmed.1000180访问这些网站。美国国家老龄化研究所为患者和护理人员提供有关健忘和阿尔茨海默病的信息（英语和西班牙语）美国国家神经系统疾病和中风研究所提供有关痴呆症的信息（英语和西班牙语）英国国家健康服务选择网站也为患者和他们的护理人员提供有关痴呆症和阿尔茨海默病的详细信息MedlinePlus提供了有关痴呆症的其他资源的链接有关英国医学研究委员会认知功能和衰老研究（MRC CFAS）的更多信息可在此获取
Researchers from the Medical Research Council Cognitive Function and Ageing Neuropathology Study carry out an analysis of brain pathologies contributing to dementia, within a cohort of elderly individuals in the UK who agreed to brain donation. Dementia drug development aims to modulate pathological processes that cause clinical syndromes. Population data (epidemiological neuropathology) will help to model and predict the potential impact of such therapies on dementia burden in older people. Presently this can only be explored through post mortem findings. We report the attributable risks (ARs) for dementia at death for common age-related degenerative and vascular pathologies, and other factors, in the MRC Cognitive Function and Ageing Study (MRC CFAS). A multicentre, prospective, longitudinal study of older people in the UK was linked to a brain donation programme. Neuropathology of 456 consecutive brain donations assessed degenerative and vascular pathologies. Logistic regression modelling, with bootstrapping and sensitivity analyses, was used to estimate AR at death for dementia for specific pathologies and other factors. The main contributors to AR at death for dementia in MRC CFAS were age (18%), small brain (12%), neocortical neuritic plaques (8%) and neurofibrillary tangles (11%), small vessel disease (12%), multiple vascular pathologies (9%), and hippocampal atrophy (10%). Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%). Such AR estimates cannot be derived from the living population; rather they estimate the relative contribution of specific pathologies to dementia at death. We found that multiple pathologies determine the overall burden of dementia. The impact of therapy targeted to a specific pathology may be profound when the dementia is relatively “pure,” but may be less impressive for the majority with mixed disease, and in terms of the population. These data justify a range of strategies, and combination therapies, to combat the degenerative and vascular determinants of cognitive decline and dementia. Please see later in the article for the Editors' Summary Losing one's belongings and forgetting people's names is often a normal part of aging. But increasing forgetfulness can also be a sign of dementia, a group of symptoms caused by several disorders that affect the structure of the brain. The commonest form of dementia is Alzheimer disease. In this, protein clumps called plaques and neurofibrillary tangles form in the brain and cause its degeneration. Vascular dementia, in which problems with blood circulation deprive parts of the brain of oxygen, is also common. People with dementia have problems with two or more “cognitive” functions—thinking, language, memory, understanding, and judgment. As the disease progresses, they gradually lose their ability to deal with normal daily activities until they need total care, their personality often changes, and they may become agitated or aggressive. Dementia is rare before the age of 65 years but about a quarter of people over 85 years old have dementia. Because more people live to a ripe old age these days, the number of people with dementia is increasing. According to the latest estimates, about 35 million people now have dementia and by 2050, 115 million may have the disorder. There is no cure for dementia but many drugs designed to modulate specific abnormal (pathological) changes in the brain that can cause the symptoms of dementia are being developed. To assess the likely impact of these potentially expensive new therapies, experts need to know what proportion of dementia is associated with each type of brain pathology. Although some brain changes can be detected in living brains with techniques such as computed tomography brain scans, most brain changes can only be studied in brains taken from people after death (post mortem brains). In this study, which is part of the UK Medical Research Council Cognitive Function and Ageing Study (MRC CFAS), the researchers look for associations between dementia in elderly people and pathological changes in their post mortem brains and estimate the attributable-risk (AR) for dementia at death associated with specific pathological features in the brain. That is, they estimate the proportion of dementia directly attributable to each type of pathology. Nearly 20 years ago, the MRC CFAS interviewed more than 18,000 people aged 65 years or older recruited at six sites in England and Wales to determine their cognitive function and their ability to deal with daily activities. 20% of the participants, which included people with and without cognitive impairment, were then assessed in more detail and invited to donate their brains for post mortem examination. As of 2004, 456 individuals had donated their brains. The dementia status of these donors was established using data from their assessment interviews and death certificates, and from interviews with relatives and carers, and their brains were carefully examined for abnormal changes. The researchers then used statistical methods to estimate the AR for dementia at death associated with various abnormal brain changes. The main contributors to AR for dementia at death included age (18% of dementia at death was attributable to this factor), plaques (8%), and neurofibrillary tangles (11%) in a brain region called the neocortex, small blood vessel disease (12%), and multiple abnormal changes in blood vessels (9%). These findings suggest that multiple abnormal brain changes determine the overall burden of dementia. Importantly, they also suggest that dementia is often associated with mixed pathological changes—many people with dementia had brain changes consistent with both Alzheimer disease and vascular dementia. Because people with dementia live for variable lengths of time during which the abnormal changes in their brain are likely to alter, it may be difficult to extrapolate these findings to living populations of elderly people. Furthermore, only a small percentage of the MRC CFAS participants have donated their brains so the findings of this study may not apply to the general population. Nevertheless, these findings suggest that the new therapies currently under development may do little to reduce the overall burden of dementia because most people's dementia involves multiple pathologies. Consequently, it may be necessary to develop a range of strategies and combination therapies to deal with the ongoing dementia epidemic. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000180. The US National Institute on Aging provides information for patients and carers about forgetfulness and about Alzheimer disease (in English and Spanish) The US National Institute of Neurological Disorders and Stroke provides information about dementia (in English and Spanish) The UK National Health Service Choices Web site also provides detailed information for patients and their carers about dementia and about Alzheimer disease MedlinePlus provides links to additional resources about dementia and Alzheimer disease (in English and Spanish) More information about the UK Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) is available
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影响因子：
11.2
作者：
Petrovitch, H;Ross, GW;White, LR
通讯作者：
White, LR
DOI：
10.1111/j.1532-5415.1992.tb02015.x
发表时间：
1992-05-01
影响因子：
6.3
作者：
MACERA, CA;SUN, RKP;BRANDES, DA
通讯作者：
BRANDES, DA
影响因子：
4.2
作者：
Ball, M;Braak, H;Khachaturian, Z
通讯作者：
Khachaturian, Z
影响因子：
11.2
作者：
Sonnen, Joshua A.;Larson, Eric B.;Montine, Thomas J.
通讯作者：
Montine, Thomas J.
影响因子：
15.8
作者：
Matthews, F;Brayne, C
通讯作者：
Brayne, C