Vos Stephanie J B, Verhey Frans, Frölich Lutz, Kornhuber Johannes, Wiltfang Jens, Maier Wolfgang, Peters Oliver, Rüther Eckart, Nobili Flavio, Morbelli Silvia, Frisoni Giovanni B, Drzezga Alexander, Didic Mira, van Berckel Bart N M, Simmons Andrew, Soininen Hilkka, Kłoszewska Iwona, Mecocci Patrizia, Tsolaki Magda, Vellas Bruno, Lovestone Simon, Muscio Cristina, Herukka Sanna-Kaisa, Salmon Eric, Bastin Christine, Wallin Anders, Nordlund Arto, de Mendonça Alexandre, Silva Dina, Santana Isabel, Lemos Raquel, Engelborghs Sebastiaan, Van der Mussele Stefan, Freund-Levi Yvonne, Wallin Åsa K, Hampel Harald, van der Flier Wiesje, Scheltens Philip, Visser Pieter Jelle
1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands
1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands.
Brain. 2015 May;138(Pt 5):1327-38. doi: 10.1093/brain/awv029. Epub 2015 Feb 17.
Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.
国际工作组-1标准、国际工作组-2标准以及美国国立衰老研究所-阿尔茨海默病协会标准。我们根据这些标准比较了轻度认知障碍阶段阿尔茨海默病的患病率和预后。从13个队列中招募了轻度认知障碍患者（n = 1607），其中766人同时具有淀粉样蛋白和神经元损伤标志物。我们使用认知测试表现和可用的生物标志物，根据国际工作组-1标准和国际工作组-2标准将受试者分类为前驱性阿尔茨海默病，并根据美国国立衰老研究所-阿尔茨海默病协会标准将其分为阿尔茨海默病高可能性组、生物标志物冲突组（孤立的淀粉样蛋白病理或疑似非阿尔茨海默病病理生理学）和阿尔茨海默病低可能性组。观察指标为轻度认知障碍阶段患阿尔茨海默病的受试者比例以及进展为阿尔茨海默病型痴呆的情况。我们使用Cox比例风险模型进行生存分析。根据国际工作组-1标准，850名（53%）受试者患有前驱性阿尔茨海默病。他们进展为阿尔茨海默病型痴呆的3年发生率为50%，而无前驱性阿尔茨海默病的受试者为21%。根据国际工作组-2标准，308名（40%）受试者患有前驱性阿尔茨海默病。他们进展为阿尔茨海默病型痴呆的3年发生率为61%，而无前驱性阿尔茨海默病的受试者为22%。根据美国国立衰老研究所-阿尔茨海默病协会标准，353名（46%）受试者属于阿尔茨海默病高可能性组，49名（6%）属于孤立淀粉样蛋白病理组，220名（29%）属于疑似非阿尔茨海默病病理生理学组，144名（19%）属于阿尔茨海默病低可能性组。阿尔茨海默病高可能性组进展为阿尔茨海默病型痴呆的3年发生率为59%，孤立淀粉样蛋白病理组为22%，疑似非阿尔茨海默病病理生理学组为24%，阿尔茨海默病低可能性组为5%。我们的研究结果支持使用所提出的研究标准来识别轻度认知障碍阶段的阿尔茨海默病。在临床环境中，按照美国国立衰老研究所-阿尔茨海默病协会标准同时使用淀粉样蛋白和神经元损伤标志物可提供最准确的预后。对于临床试验，可以考虑选择美国国立衰老研究所-阿尔茨海默病协会高可能性组或国际工作组-2前驱性阿尔茨海默病组的受试者。
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