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文献精选 > 高引权威"阿尔茨海默病"文献

Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. ​

文献信息 ​

DOI10.1016/j.jalz.2011.03.003
PMID21514248
期刊Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子11.1
JCR 分区Q1
发表年份2011
被引次数3449
关键词阿尔茨海默病, 前临床阶段, 生物标志物, 认知障碍, 干预措施
文献类型Consensus Development Conference, NIH, Journal Article, Research Support, Non-U.S. Gov't
ISSN1552-5260
页码280-92
期号7(3)
作者Reisa A Sperling, Paul S Aisen, Laurel A Beckett, David A Bennett, Suzanne Craft, Anne M Fagan, Takeshi Iwatsubo, Clifford R Jack, Jeffrey Kaye, Thomas J Montine, Denise C Park, Eric M Reiman, Christopher C Rowe, Eric Siemers, Yaakov Stern, Kristine Yaffe, Maria C Carrillo, Bill Thies, Marcelle Morrison-Bogorad, Molly V Wagster, Creighton H Phelps

一句话小结 ​

本研究探讨了阿尔茨海默病（AD）在临床前阶段的病理过程与临床症状之间的联系，通过综合生物标志物、流行病学和神经心理学的证据，提出了一个概念框架和操作性研究标准，以预测从正常认知到轻度认知障碍及AD痴呆症的进展风险。该框架旨在推动临床前AD的研究，支持早期干预策略的开发，以期在疾病的某个阶段实现有效的治疗。

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阿尔茨海默病 · 前临床阶段 · 生物标志物 · 认知障碍 · 干预措施

摘要 ​

阿尔茨海默病（AD）的病理生理过程被认为在诊断出AD痴呆症之前的许多年就已开始。这一漫长的“临床前”阶段为治疗干预提供了关键机会；然而，我们需要进一步阐明AD的病理级联与临床症状出现之间的联系。美国国立衰老研究所和阿尔茨海默协会召集了一个国际工作组，审查生物标志物、流行病学和神经心理学的证据，并制定建议，以确定最佳预测“正常”认知向轻度认知障碍及AD痴呆症进展风险的因素。我们提出了一个概念框架和操作性研究标准，基于迄今为止的主流科学证据，旨在通过纵向临床研究来测试和完善这些模型。这些建议仅用于研究目的，目前没有任何临床意义。希望这些建议能够提供一个共同的框架，以推动临床前AD的研究，最终帮助该领域朝向在AD的某个阶段进行早期干预，在这一阶段某些疾病修饰疗法可能是最有效的。

英文摘要 ​

The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.

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主要研究问题 ​

  1. 在定义阿尔茨海默病的前临床阶段时，是否有特定的生物标志物被认为是最重要的预测因子？
  2. 研究人员如何评估正常认知到轻度认知障碍的转变过程中，神经心理学证据的作用？
  3. 除了生物标志物，还有哪些其他因素可能影响阿尔茨海默病的早期干预策略？
  4. 在进行纵向临床研究时，如何确保所提出的操作性研究标准能够有效地被测试和验证？
  5. 当前有哪些正在进行的研究项目或试验，旨在探讨阿尔茨海默病的前临床阶段及其干预措施？

核心洞察 ​

研究背景和目的 ​

阿尔茨海默病（AD）的病理过程被认为在临床痴呆症状出现前的许多年就已开始。这一“前临床”阶段为治疗干预提供了关键机会，因此需要进一步阐明AD的病理级联与临床症状出现之间的联系。国家老龄化研究所和阿尔茨海默协会召集国际工作组，回顾生物标志物、流行病学和神经心理学证据，制定建议以确定最佳预测从“正常”认知到轻度认知障碍（MCI）及AD痴呆的风险因素。

主要方法/材料/实验设计 ​

研究采用以下方法：

  1. 文献回顾：对现有的生物标志物、流行病学数据和神经心理学研究进行综合分析。
  2. 框架提出：提出一个概念框架和操作性研究标准，旨在为前临床AD的研究提供共同语言。
Mermaid diagram

关键结果和发现 ​

  1. 病理过程的时间延迟：AD的病理过程可能在临床症状出现前的十年或更早就已开始，特别是淀粉样β（Aβ）沉积。
  2. 生物标志物的发现：通过神经影像学和脑脊液（CSF）检测，发现许多临床正常的老年人已表现出Aβ积累的证据。
  3. 认知变化的预测：有证据表明，Aβ阳性但无临床症状的个体在认知功能上可能会出现细微的变化，这些变化可能在MCI出现前的十年内被检测到。

主要结论/意义/创新性 ​

研究强调了在AD的前临床阶段进行干预的重要性，建议通过生物标志物来识别高风险个体，以便在临床症状出现之前进行治疗。这一框架为未来的研究提供了基础，可能会改变AD的早期干预策略。

研究局限性和未来方向 ​

  1. 局限性：当前的生物标志物仍然是“代理”指标，可能无法完全反映活体大脑中的生物过程。此外，许多研究样本可能存在选择偏差，无法代表一般老年人群体。
  2. 未来方向：需要开发新的生物标志物和认知测评工具，以便更好地检测早期临床症状，并进行长期的纵向研究以确认预测模型的有效性。

研究阶段分类 ​

研究建议的分类框架如下：

阶段描述
阶段1无症状的脑内淀粉样蛋白沉积
阶段2脑内淀粉样蛋白沉积 + 神经元损伤证据
阶段3脑内淀粉样蛋白沉积 + 神经元损伤 + 轻微认知下降

这一分类将有助于研究人员选择适当的研究人群，并优化干预策略。

参考文献 ​

  1. Depressive symptoms and cognitive decline in late life: a prospective epidemiological study. - Mary Ganguli;Yangchun Du;Hiroko H Dodge;Graham G Ratcliff;Chung-Chou H Chang - Archives of general psychiatry (2006)
  2. Frequent amyloid deposition without significant cognitive impairment among the elderly. - Howard Jay Aizenstein;Robert D Nebes;Judith A Saxton;Julie C Price;Chester A Mathis;Nicholas D Tsopelas;Scott K Ziolko;Jeffrey A James;Beth E Snitz;Patricia R Houck;Wenzhu Bi;Ann D Cohen;Brian J Lopresti;Steven T DeKosky;Edythe M Halligan;William E Klunk - Archives of neurology (2008)
  3. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. - Christopher C Rowe;Kathryn A Ellis;Miroslava Rimajova;Pierrick Bourgeat;Kerryn E Pike;Gareth Jones;Jurgen Fripp;Henri Tochon-Danguy;Laurence Morandeau;Graeme O'Keefe;Roger Price;Parnesh Raniga;Peter Robins;Oscar Acosta;Nat Lenzo;Cassandra Szoeke;Olivier Salvado;Richard Head;Ralph Martins;Colin L Masters;David Ames;Victor L Villemagne - Neurobiology of aging (2010)
  4. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. - Leslie M Shaw;Hugo Vanderstichele;Malgorzata Knapik-Czajka;Christopher M Clark;Paul S Aisen;Ronald C Petersen;Kaj Blennow;Holly Soares;Adam Simon;Piotr Lewczuk;Robert Dean;Eric Siemers;William Potter;Virginia M-Y Lee;John Q Trojanowski; - Annals of neurology (2009)
  5. Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. - S M Resnick;J Sojkova;Y Zhou;Y An;W Ye;D P Holt;R F Dannals;C A Mathis;W E Klunk;L Ferrucci;M A Kraut;D F Wong - Neurology (2010)
  6. Selective disruption of the cerebral neocortex in Alzheimer's disease. - Rahul S Desikan;Mert R Sabuncu;Nicholas J Schmansky;Martin Reuter;Howard J Cabral;Christopher P Hess;Michael W Weiner;Alessandro Biffi;Christopher D Anderson;Jonathan Rosand;David H Salat;Thomas L Kemper;Anders M Dale;Reisa A Sperling;Bruce Fischl; - PloS one (2010)
  7. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. - Anne M Fagan;Catherine M Roe;Chengjie Xiong;Mark A Mintun;John C Morris;David M Holtzman - Archives of neurology (2007)
  8. Serial MRI and CSF biomarkers in normal aging, MCI, and AD. - P Vemuri;H J Wiste;S D Weigand;D S Knopman;J Q Trojanowski;L M Shaw;M A Bernstein;P S Aisen;M Weiner;R C Petersen;C R Jack; - Neurology (2010)
  9. Abeta deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer's disease. - V L Villemagne;K E Pike;D Darby;P Maruff;G Savage;S Ng;U Ackermann;T F Cowie;J Currie;S G Chan;G Jones;H Tochon-Danguy;G O'Keefe;C L Masters;C C Rowe - Neuropsychologia (2008)
  10. Predictors of maintaining cognitive function in older adults: the Health ABC study. - K Yaffe;A J Fiocco;K Lindquist;E Vittinghoff;E M Simonsick;A B Newman;S Satterfield;C Rosano;S M Rubin;H N Ayonayon;T B Harris; - Neurology (2009)

引用本文的文献 ​

  1. Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults. - B C Dickerson;T R Stoub;R C Shah;R A Sperling;R J Killiany;M S Albert;B T Hyman;D Blacker;L Detoledo-Morrell - Neurology (2011)
  2. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. - Marilyn S Albert;Steven T DeKosky;Dennis Dickson;Bruno Dubois;Howard H Feldman;Nick C Fox;Anthony Gamst;David M Holtzman;William J Jagust;Ronald C Petersen;Peter J Snyder;Maria C Carrillo;Bill Thies;Creighton H Phelps - Alzheimer's & dementia : the journal of the Alzheimer's Association (2011)
  3. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. - Guy M McKhann;David S Knopman;Howard Chertkow;Bradley T Hyman;Clifford R Jack;Claudia H Kawas;William E Klunk;Walter J Koroshetz;Jennifer J Manly;Richard Mayeux;Richard C Mohs;John C Morris;Martin N Rossor;Philip Scheltens;Maria C Carrillo;Bill Thies;Sandra Weintraub;Creighton H Phelps - Alzheimer's & dementia : the journal of the Alzheimer's Association (2011)
  4. Face-name associative memory performance is related to amyloid burden in normal elderly. - Dorene M Rentz;Rebecca E Amariglio;J Alex Becker;Meghan Frey;Lauren E Olson;Katherine Frishe;Jeremy Carmasin;Jacqueline E Maye;Keith A Johnson;Reisa A Sperling - Neuropsychologia (2011)
  5. Neuroimaging markers for the prediction and early diagnosis of Alzheimer's disease dementia. - Michael Ewers;Reisa A Sperling;William E Klunk;Michael W Weiner;Harald Hampel - Trends in neurosciences (2011)
  6. Progress in Alzheimer's disease. - Daniela Galimberti;Elio Scarpini - Journal of neurology (2012)
  7. Role of cerebrospinal fluid and plasma biomarkers in the diagnosis of neurodegenerative disorders and mild cognitive impairment. - Luis F Gonzalez-Cuyar;Joshua A Sonnen;Kathleen S Montine;C Dirk Keene;Thomas J Montine - Current neurology and neuroscience reports (2011)
  8. Perspective: prevention is better than cure. - Sam Gandy - Nature (2011)
  9. Perspective: in search of biomarkers. - Neil S Buckholtz - Nature (2011)
  10. Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer's disease. - Clifford R Jack;Frederik Barkhof;Matt A Bernstein;Marc Cantillon;Patricia E Cole;Charles Decarli;Bruno Dubois;Simon Duchesne;Nick C Fox;Giovanni B Frisoni;Harald Hampel;Derek L G Hill;Keith Johnson;Jean-François Mangin;Philip Scheltens;Adam J Schwarz;Reisa Sperling;Joyce Suhy;Paul M Thompson;Michael Weiner;Norman L Foster - Alzheimer's & dementia : the journal of the Alzheimer's Association (2011)

... (3439 更多 篇文献)

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