Framework : Towards a Biological Definition of Alzheimer ’ s Disease 1 2 draft 9-19-17 3 4 5
Framework : Towards a Biological Definition of Alzheimer ’ s Disease 1 2 draft 9-19-17 3 4 5
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发表时间：
2017
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通讯作者：
C. Jack;D. Bennett;K. Blennow;B. Dunn;C. Elliott;S. Haeberlein;D. Holtzman;M. Jagust;F. Jessen-F.
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作者：
C. Jack;D. Bennett;K. Blennow;B. Dunn;C. Elliott;S. Haeberlein;D. Holtzman;M. Jagust;F. Jessen-F.
2011年，美国国家老龄研究所和阿尔茨海默病协会（NIA - AA）针对阿尔茨海默病的临床前、轻度认知障碍以及痴呆阶段制定了18条不同的诊断建议。在此期间的科学进展促使NIA - AA发起一项行动，对2011年的指南进行更新和统一。这一统一更新被称为“研究框架”，因为其预期用途是用于观察性和干预性研究，而非常规临床护理。在NIA - AA研究框架中，阿尔茨海默病（AD）是由其潜在的病理过程所定义的，这些病理过程可通过尸检或体内生物标志物来记录。在这个研究框架中，诊断并非基于疾病的临床后果（即症状/体征），这使得对活体患者阿尔茨海默病的诊断从综合征转变为生物学构建。该研究框架侧重于利用生物标志物对活体患者进行阿尔茨海默病的诊断。生物标志物分为β - 淀粉样蛋白沉积、病理性tau蛋白和神经退行性变这几类。文中描述了两种认知分期方案：一种采用3种传统综合征类别，另一种是6阶段数字方案。我们设想，将阿尔茨海默病定义为一种生物学构建，将能够更准确地描述和理解导致认知障碍的事件顺序以及痴呆的多因素病因。这种方法还将使干预性试验能够更精确地进行，在疾病过程中以及针对合适的人群可以靶向特定的途径。重要的是，应在更多样化的人群中确定这种构建的有效性。
17 In 2011 the National Institute on Aging and Alzheimer’s Association (NIA-AA) created 18 separate diagnostic recommendations for the preclinical, mild cognitive impairment, and 19 dementia stages of Alzheimers disease. Scientific progress in the interim led to an initiative by 20 the NIA-AA to update and unify the 2011 guidelines. This unifying update is labeled a “research 21 framework”, because its intended use is for observational and interventional research, not routine 22 clinical care. In the NIA AA research framework Alzheimer’s disease (AD) is defined by its 23 underlying pathologic processes which can be documented by post-mortem examination or in 24 vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e. 25 symptoms/signs) in this research framework which shifts the diagnosis of AD in living people 26 from a syndromal to a biological construct. The research framework focuses on the diagnosis of 27 AD with biomarkers in living persons. Biomarkers are grouped into those of β-amyloid 28 deposition, pathologic tau, and neurodegeneration. Two cognitive staging schemes are described: 29 a scheme employing 3 traditional syndromal categories and a 6 stage numeric scheme. We 30 envision that defining AD as a biological construct will enable a more accurate characterization 31 DRAFT – AS of September 19, 2017 DO NOT REPRODUCE and understanding of the sequence of events that lead to cognitive impairment as well as the 32 multi factorial etiology of dementia. This approach also will enable a more precise approach to 33 interventional trials where specific pathways can be targeted in the disease process and in the 34 appropriate people. Importantly, the validity of this construct should be determined in more 35 diverse populations. 36