阿尔兹海默症诊断新标准

1、NEW CRITERIA AND GUIDELINES FOR THE DIAGNOSIS OF ALZHEIMERS DISEASE PUBLISHED FOR FIRST TIME IN 27 YEARS - Research Agenda Suggested for Detecting Pre-Symptomatic Alzheimers - New Alzheimers Definition Moves Researchers Closer to Early Detection and Intervention CHICAGO, April 19, 2011 For the first

2、 time in 27 years, new criteria and guidelines for the diagnosis of Alzheimers disease have been published by three expert workgroups spearheaded by the Alzheimers Association and the National Institute on Aging (NIA) of the National Institutes of Health (NIH).The workgroups published four articles

3、including ready-to-use clinical diagnostic criteria for Alzheimers disease dementia and mild cognitive impairment (MCI) due to Alzheimers. A research agenda was proposed for preclinical Alzheimers. The use of biomarkers in Alzheimers dementia and MCI due to Alzheimers was also proposed as a research

4、 agenda only, and is not intended for application in clinical settings at this time.The articles collectively, the National Institute on Aging/Alzheimers Association Diagnostic Guidelines for Alzheimers Disease expand the definition of Alzheimers to include two new phases of the disease: (1) presymp

5、tomatic and (2) mildly symptomatic but pre-dementia, along with (3) dementia caused by Alzheimers. This reflects current thinking that Alzheimers begins creating distinct and measurable changes in the brains of affected people years, perhaps decades, before memory and thinking symptoms are noticeabl

6、e.“It is our hope that incorporating scientific knowledge gained and technological advances made over the past quarter century will improve current diagnosis, bring the field closer to earlier detection and treatment, and ultimately lead to effective disease-modifying therapies,” said William Thies,

7、 Ph.D., Chief Medical and Scientific Officer at the Alzheimers Association. “Development and publication of these articles is a major landmark in the field. That said, publication of these articles is not yet the end of the process of developing new diagnostic criteria for Alzheimers, but is another

8、 major step in the process.”“The new guidelines reflect todays understanding of how key changes in the brain lead to Alzheimers disease pathology and how they relate to the clinical signs of mild cognitive impairment and Alzheimers disease dementia,” said Creighton Phelps, Ph.D., Program Director of

9、 the Alzheimers Disease Centers Program at the National Institutes of Health. “We are also beginning to be able to detect these changes at a preclinical stage, long before symptoms appear in many people. With further research on biomarkers, as set forth in the new guidelines, we may ultimately be ab

10、le to predict who is at risk for development of mild cognitive impairment and Alzheimers dementia, and who would benefit most as interventions are developed.”The proposed new Alzheimers disease diagnostic guidelines were published online today by Alzheimers & Dementia: The Journal of the Alzheim

11、ers Association. Hard copy publication is scheduled for the May 2011 issue of the journal.Three Stages of Alzheimers DiseaseThe current diagnostic criteria for Alzheimers*, for the most part, focus on reliable diagnosis when signs of problems in thinking, learning, and memory are noticeable to an in

12、dividual, family, and friends. But research tells us that Alzheimers likely begins years, maybe even decades, prior to symptoms appearing.The new articles refer to three phases of Alzheimers disease progression over time:Preclinical Alzheimers Disease Measurable changes in biomarkers (such as brain

13、imaging and spinal fluid chemistry) that indicate the very earliest signs of disease, before outward symptoms are visible. Currently, there are no clinical diagnostic criteria for this phase, but the group provides a scientific framework to help researchers better define this stage of Alzheimers. (S

14、ee supplement 5.)Mild cognitive impairment (MCI) due to Alzheimers Disease Mild changes in memory and thinking abilities, enough to be noticed and measured, but not impairment that compromises everyday activities and functioning. Dementia due to Alzheimers Disease Memory, thinking and behavioral sym

15、ptoms that impair a persons ability to function in daily life. (For more details, see supplement 3.)According to the authors, in order to facilitate the possibility of future presymptomatic treatment of Alzheimers, it was important to define the disease from the earliest changes in the brain, not on

16、ly the observable, symptomatic stages of the disease. The authors propose that Alzheimers begins with a long asymptomatic period during which detrimental changes are progressing in the brain, and individuals with biomarker evidence of these changes are at increased risk for developing cognitive and

17、behavioral impairment and progression to Alzheimers dementia.A biomarker is a naturally occurring, measurable substance or condition in the body that reliably indicates the presence or absence of disease or the risk of later developing a disease; for example, blood glucose levels are a biomarker of

18、diabetes, and cholesterol levels are a biomarker of cardiovascular disease risk. Both fluid and imaging measures are being tested as possible biomarkers for Alzheimers. (See supplement 4.)There was a broad consensus within the workgroups that much additional research needs to be done to validate the

19、 application of biomarkers as they are proposed in the newly-published articles. According to the authors, “The definitive studies are likely to take more than a decade to fully accomplish. Thus, we must move quickly and adjust our models and study designs as new data become available.” “If we can d

20、efinitively determine the risk of developing Alzheimers dementia in people who have biomarker evidence of brain changes but are not showing outward symptoms, we will open an important window of opportunity to intervene with disease-modifying therapies, once they are developed,” Thies said.“In additi

21、on, the new criteria give us powerful tools to accelerate our knowledge in the fight against Alzheimers disease. They give us guidelines for getting a more accurate assessment of Alzheimers prevalence. In that way we can better assess the need for everything from research dollars to care services, t

22、o patient and caregiver education materials, to nursing home beds, to the number of gerontologists and nurses that we need. And, they give us a basis for creating the next generation of Alzheimers treatments that will be effective in each stage of the disease,” Thies said.Moving the Field Toward Ear

23、lier Diagnosis and Treatment of AlzheimersThe Alzheimers Association, in its 2010 report titled “Changing the Trajectory of Alzheimers Disease: A National Imperative,” showed that a hypothetical intervention that delayed the onset of Alzheimers dementia by five years would result in a nearly 45 perc

24、ent reduction in the number of people with Alzheimers by 2050, and reduce the projected Medicare costs of Alzheimers from $627 billion to $344 billion dollars. The authors of the newly-released articles write, “It is our hope that the advances in preclinical detection of Alzheimers will enable earli

25、er, more effective treatment, just as nearly all of therapeutic gains in cancer, cardiovascular disease, osteoporosis, and diabetes involve treatment before significant clinical symptoms are present. Screening and treatment programs instituted for other diseases have already been associated with a d

26、ecrease in mortality due to these conditions.”Thies adds, “Currently, Alzheimers therapies are in development that may be able to slow or stop the progression of the disease. By improving early detection and risk evaluation, we will better be able to test potential therapies and eventually prescribe

27、 them for people at increased risk. Ultimately, this approach envisions for Alzheimers what is now common practice in cardiovascular disease, where early signs of risk for example, in genetic markers or in blood cholesterol and/or blood pressure levels can be treated to reduce the likelihood of hear

28、t attack or stroke later on.”The challenge for Alzheimers now is that there is currently no single, generally accepted way to identify the disease in the earliest stage before symptoms are evident. It is hoped that the research agenda outlined in the new preclinical Alzheimers article will correct t

29、his deficit.Presymptomatic Disease Detection and Treatment Not a New Idea, Except in AlzheimersAccording to the authors, “The concept of a preclinical phase of disease should not be too foreign. Medical professionals readily acknowledge that cancer can be detected at the stage of carcinoma in situ a

30、nd that hypercholesterolemia and atherosclerosis can result in narrowing of coronary arteries that is detectable prior to myocardial infarction. It is widely acknowledged that symptoms are not necessary to diagnose human disease. Type II diabetes, hypertension, renal insufficiency, and osteoporosis

31、are frequently detected through laboratory tests, and effective treatment can prevent the emergence of symptoms.”“We should be open to the idea that Alzheimers could one day be diagnosed preclinically by the presence of biomarker evidence, which may eventually guide therapy prior to the onset of sym

32、ptoms. We treat people with diabetes, elevated cholesterol, hypertension and a variety of other illnesses we do not wait for strokes, heart attacks or other long term complications that we know will occur in significant numbers of those affected. Similarly, our intention is to use these criteria to

33、better determine an individuals risk of developing Alzheimers disease. This diagnostic research will help us discover the drugs of the future and prepare for the day when we can administer them to those at risk in order to prevent or delay the emergence of symptoms,” wrote the authors.What Was Publi

34、shedThe proposed new diagnostic criteria and research agenda for Alzheimers disease are presented in three documents, plus an introduction. One workgroup updated the 1984 diagnostic criteria for the dementia due to Alzheimers disease. Guy McKhann, M.D., Johns Hopkins University School of Medicine, B

35、altimore, and David Knopman, M.D., Mayo Clinic, Rochester, Minn., co-chaired this panel.A second workgroup focused on refining the criteria for the symptomatic, pre-dementia phase, referred to as Mild Cognitive Impairment due to Alzheimers disease. Marilyn Albert, Ph.D., Johns Hopkins University Sch

36、ool of Medicine, Baltimore, chaired this workgroup.The third workgroup proposed a research agenda (NOT criteria for clinical diagnosis; this is an important distinction. See supplement 4.) for the asymptomatic, preclinical phase of Alzheimers. Reisa Sperling, M.D, Brigham and Women's Hospit

37、al, Harvard Medical School, Boston, chaired this group.The introduction provides an overview of the changes that have occurred in the Alzheimers field since the first diagnostic criteria were published in 1984, and outlines future challenges that need to be addressed. Clifford Jack, M.D., Mayo Clini

38、c, Rochester, Minn., is lead author of this article. Preliminary recommendations were announced in July 2010 at the Alzheimers Association International Conference on Alzheimers Disease (AAICAD). These early drafts were then made available for comment on the Alzheimers Association website, along wit

39、h further presentation and discussion at a variety of medical and scientific meetings.The three sets of recommendations differ in terms of relevance to current clinical practice. The clinical diagnostic criteria for Alzheimers dementia and MCI due to Alzheimers are intended to guide diagnosis in the

40、 current clinical setting, such as a doctors office, including settings where no access to testing for biomarkers exists.The use of biomarkers in both Alzheimers dementia and MCI due to Alzheimers disease is intended only for research at this time. However, some biomarkers, especially those using ad

41、vanced imaging techniques, could enter clinical practice in the near future, though much remains to be learned about their utility in this setting.The recommendations of the preclinical Alzheimers workgroup are intended for research purposes only, and do not have any clinical utility at this time. A

42、 fourth workgroup has been organized to examine the postmortem, pathological criteria for Alzheimers. The results of their deliberations are expected to appear later in 2011. 27年内首次出版发行的阿尔茨海默病诊断的新标准和指南 -研究建议检测症状前的阿尔茨海默病-新的阿尔茨海默病的定义促使研究者进行阿尔茨海默病早期的筛查和干预-2011年4月19日，以阿尔茨海默病协会和国立卫生院(NIH)的国家老年研究所(NIA)为先锋

43、的三个专家工作组在芝加哥于27年内首次发布了诊断阿尔茨海默病的新标准和指南。工作组发行了随时可用的4项关于阿尔茨海默病痴呆和由于阿尔茨海默病导致的轻度认知障碍(MCI)的临床诊断标准。提出的一项研究主题是关于临床前的阿尔茨海默病。关于阿尔茨海默病痴呆和由于阿尔茨海默病导致痴呆的生物标记物的使用问题仅作为一项研究议题被提出，此次未意图于其在临床中的使用。这些条目-总体而言，国家老年研究所/阿尔茨海默病协会阿尔茨海默病诊断指南-扩展阿尔茨海默病定义使其包括此病的两个新的阶段：临床症状前和轻度的症状但尚处于痴呆前的阶段以及由阿尔茨海默病导致的失智症。这反映了当前的这样的观点：阿尔茨海默病患者在记忆和

44、思维症状出现以前的数十年里脑中可以先产生明显的可测量的变化。阿尔茨海默病协会首席官员，哲学博士William Thies 说：“我们希望过去四分之一世纪里科学技术所取得的进步将有助于提高目前的诊断，带动这个领域的更早的检查和治疗，最终导致有效的病性改善疗法”，“这些条目的发展和出版是这个领域的重要的里程碑。也就是说，这些条目的发展和出版不是新的阿尔茨海默病诊断标准发展过程的结束，而是这个过程中重要的一步”。国家健康协会的阿尔茨海默病中心项目的项目总监，哲学博士Creighton Phelps说“新的指南反映了时下关于脑中导致阿尔茨海默病的关键病理变化和他们与轻度认知障碍及阿尔茨海默病失智症的临

45、床体征之间的关系”，“我们已经可以在临床症状出现前的阶段对这些病理改变进行检测，许多病人在此后很久才出现临床症状。如新指南中所述，随着关于生物标记物的进一步的研究，我们将最终可以预测哪些人具有发展为轻度认知障碍和阿尔茨海默病痴呆的危险，以及哪些人可以从干预措施的发展中获益最多”。所推荐的新的阿尔茨海默病指南今天由阿尔茨海默病协会主办杂志Alzheimers & Dementia在线出版。纸质版已安排在此杂志的2011年的5月份出版。阿尔茨海默病的三个分期目前的阿尔茨海默病的诊断标准通常确定诊断依赖于当个人、家庭或是朋友注意到其在思考、学习和记忆方面的症状。但是研究告诉我们，阿尔茨海默病

46、可能在患者出现症状前数年甚至是数十年已经开始发病。新的条目涉及阿尔茨海默病随着时间推移发展的三个阶段：阿尔茨海默病临床前-可测量的生物标记物（譬如脑部影像学和脑脊液化学检测）的变化在外部的症状可见之前表明疾病最早阶段的征象。目前没有这个阶段的临床诊断标准，但是工作组提供了一个科学的框架帮助研究者更好的定义阿尔茨海默病的这个阶段。（见附录5.）。由于阿尔茨海默病导致的轻度认知障碍-在记忆和思考能力方面的轻微的变化，足以被注意和评估，但是损害还不至于影响日常活动和功能。由阿尔茨海默病导致的失智症-记忆、思考和行为症状损害到病人的日常生活的躯体功能。（更多的细节详见附录3）为了将来便于对阿尔茨海默病

47、进行症状前治疗，作者认为对疾病最早期的脑的改变进行定义是很重要的，不只是疾病可以看见的、有症状的阶段。作者提出在阿尔茨海默病开始阶段伴随着一个长时期的非症状的阶段，在此阶段脑中有害的变化在进展，具有这些变化的生物标记物证据的个体发展为认知和行为损害的风险及进展为阿尔茨海默病痴呆的风险在增加。生物标记物是自然发生，可以测量的物质，或者说是人体内可以可靠的表明疾病存在与否或之后发展为疾病的风险的状况。例如，血糖水平是糖尿病的生物标记物，胆固醇水平是心血管疾病风险的生物标记物。体液和影像学检测均被检测作为阿尔茨海默病的可能的生物标记物。（见附录4）因为生物标记物在新近出版发行的文章中被提出，所以工作

48、组内取得了广泛一致的同意，都认为需要更多的研究去验证其应用。根据作者的观点：“决定性的研究有可能需要十年去完成实现。因此，我们必须快速的行动并且因为新的数据已经可用所以我们必须调整我们的模型和研究设计”。Thies 说：“如果我们可以最终判定那些具有脑部改变的生物标记物的证据而没有外在症状表现的具有发展为阿尔茨海默病痴呆的人群的风险，一旦他们的病情发展，我们将可以打开一个用病性改善疗法干预的机会的重要的窗口”。“另外，新的标准给了我们强有力的工具去加速我们与阿尔茨海默病战斗的知识的更新。他们给予我们一个关于阿尔茨海默病流行情况的更精确的评估的指南。这样我们可以更好的评估包括护理、病人和照料者教

49、育资料、疗养院床位、需要的老年病学专家及护士等等相关各种费用。并且，他们给我们提供了关于创造在其各个阶段均有效的下一代阿尔茨海默病治疗方法的基础”。目标转向阿尔茨海默性的更早的诊断和治疗阿尔茨海默病协会在其2010年拟题为：“改变阿尔茨海默病的轨迹：一个国家的需要”的报告表明假设干预可以将阿尔茨海默病的发病向后推迟5年，则在2050年可以将阿尔茨海默病患者的数量减少将近45%，并且将阿尔茨海默病的计划的医疗费用由6270亿美元减少到3440亿美元。”新发行的论文的作者写道：“我们希望阿尔茨海默病临床前得检测的进步可以有助于更早更有效的治疗，就像最近肿瘤、心血管疾病、骨质疏松症、糖尿病在临床出现

50、显著症状前几乎所有的治疗方面的有益进展。其他疾病筛查和治程序的实施已经可以减少这些疾病的死亡率”。Thies补充说：“目前，阿尔茨海默病治疗的进步可能可以减慢或者是阻止疾病的进展。通过提高早期的检测和风险评估，我们可以更好的检验潜在的治疗方法并且最终可以将他们处方给那些发病风险不断增加的患者。基本上这些为阿尔茨海默病设想的方法在目前的心血管疾病中是很常见的，在心血管疾病中，诸如基因标志物或血浆胆固醇和/或血压水平等早期的风险征象可以被治疗，由此可以减少心脏病发作或者是之后的卒中发作的可能性。”对于阿尔茨海默病的挑战是目前没有单独的、可以普遍接受的方法去在疾病症状出现之前的最早期识别它。希望新的

51、临床前的阿尔茨海默病的文章所概述的研究主题可以纠正这个缺点。症状发生前的疾病的检测和治疗-除了在阿尔茨海默病，已经不是一个什么新思路据作者所讲：“一个疾病临床前阶段的概念不应该与疾病太不相关。医学专家容易接受癌症可以在原位癌的阶段被检测到和高胆固醇血症及动脉粥样硬化可以导致冠状动脉狭窄而冠状动脉狭窄可以在心肌梗塞之前被检测到的观点。症状并非诊断疾病的必要条件的观点已经被公认。2型糖尿病、高血压、肾功能不全和骨质疏松症常是通过实验室检测被发现，有效的治疗可以阻止疾病症状的出现。”作者写道：“我们应该接受阿尔茨海默病有一天可以通过生物标记物出现的证据在临床前被诊断，而这将最终可引导在疾病症状出现前

52、进行治疗。我们治疗糖尿病、高胆固醇血症、高血压和很多其他疾病的患者，而不是等到一定要出现受这些疾病影响而发生卒中、心脏病发作或者其他长期的并发症出现时才进行治疗。同样的，我们的目的是运用这些标准去更好的判定一个人发展为阿尔茨海默病的风险。这个诊断将有助于我们发现将来的药物并且为我们能够把他们使用于有风险的病人以阻止或者推迟症状的出现的这么一天做准备。”已经出版发行的内容推荐的新的阿尔茨海默病的诊断标准和研究主题通过三个文档提供，还包括一份引言。由于阿尔茨海默病的缘故一个工作组于1984年更新了痴呆的诊断标准。美国约翰斯·霍普金斯大学的医学博士Guy McKhann，明尼苏达州罗彻斯特

53、市梅约医学中心的医学博士Baltimore和David 共同主持了这项工作。第二个工作组专注于对症状性的、痴呆前阶段，即由于阿尔茨海默病导致的所谓的轻度认知功能障碍的标准改善工作。第三个工作组提出了一个关于阿尔茨海默病的非症状性的、临床前阶段的研究主题（不是用于临床诊断的标准；这是一项重要的区别。见附录4.）引言部分对1984年第一个诊断标准发行后的阿尔茨海默病领域发生的变化进行了综述，并勾勒了将来必须解决的挑战。初步的推荐规范在2010年7月的阿尔茨海默病协会主办的国际阿尔茨海默病会议中宣布。这些早期的草稿之后可在阿尔茨海默病协会的网站中进行评论，并且还在各种医学和科学会中中进行了展示和讨论

54、。推荐规范的三个部分与当前的临床实践不同。阿尔茨海默病和由于阿尔茨海默病导致的痴呆的临床诊断标准是为了引导目前背景下的诊断，譬如在医生的办公室，也包括在无法测得病人的生物标记物的环境中使用。在这里生物标记物在阿尔茨海默病和由于阿尔茨海默病导致的痴呆中只是用于研究。然而，一些生物标记物，特别是那些使用先进的影像学技术的，可以进入临床实践在不远的将来，尽管许多仍需要研究他们在此情况中的实用性。临床前阿尔茨海默病的推荐规范目的只是用于研究，并且在此时并没有临床实用性。 已经组织了第四个工作组对事后析误和阿尔茨海默病的病理标准进行检验。他们商议的结果将有望与2011年年内的稍后公布。 NEW CRIT

55、ERIA AND GUIDELINES FOR THE DIAGNOSIS OF ALZHEIMERS DISEASE PUBLISHED FOR FIRST TIME IN 27 YEARS 27年内首次出版发行的阿尔茨海默病诊断的新标准和指南 - Research Agenda Suggested for Detecting Pre-Symptomatic Alzheimers -New Alzheimers Definition Moves Researchers Closer to Early Detection and Intervention -研究建议检测症状前的阿尔茨海默病-新

56、的阿尔茨海默病的定义促使研究者进行阿尔茨海默病早期的筛查和干预-CHICAGO, April 19, 2011 For the first time in 27 years, new criteria and guidelines for the diagnosis of Alzheimers disease have been published by three expert workgroups spearheaded by theAlzheimers Association and the National Institute on Aging (NIA) of the Nationa

57、l Institutes of Health (NIH).2011年4月19日，以阿尔茨海默病协会和国立卫生院(NIH)的国家老年研究所(NIA)为先锋的三个专家工作组在芝加哥于27年内首次发布了诊断阿尔茨海默病的新标准和指南。The workgroups published four articles including ready-to-use clinical diagnostic criteria for Alzheimers disease dementia and mild cognitive impairment (MCI) due to Alzheimers. A resear

58、ch agenda was proposed for preclinical Alzheimers. The use of biomarkersin Alzheimers dementia and MCI due to Alzheimers was also proposed as a research agenda only, and is not intended for application in clinical settings at this time.工作组发行了随时可用的4项关于阿尔茨海默病痴呆和由于阿尔茨海默病导致的轻度认知障碍(MCI)的临床诊断标准。提出的一项研究主题是关于临床前的阿尔茨海默病。关于阿尔茨海默病痴呆和由于阿尔茨海默病导致痴呆的生物标记物的使用问题仅作为一项研究议题被提出，此次未意图于其在临床中的使用。The articles collectively, the National Institute on Aging/Alzheimers Association Diagnostic Guidelines for Alzheimers Disease expandthe definition of Alzheimers t