本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2310168

摘要内容如下：

背景

发生在正常认知和诊断为散发性阿尔茨海默病之间的生物标志物变化尚未在纵向研究中进行广泛调查。

方法

我们对2000年1月至2020年12月参加中国认知与衰老研究的认知正常参与者进行了阿尔茨海默病生物标志物的多中心、巢式病例对照研究。这些参与者中的一个亚组每隔2至3年接受一次脑脊液（CSF）检测、认知评估和脑成像。共有648名患有阿尔茨海默病的参与者与648名认知正常的参与者相匹配，并对两组的脑脊液生化标记物浓度、认知测试和成像的时间轨迹进行分析。

结果

中位随访时间为19.9年（四分位间距为19.5至20.2）。阿尔茨海默病组的脑脊液和影像学生物标志物与认知正常组的差异在诊断前的估计年数如下：β淀粉样蛋白（Aβ）42，18岁；Aβ42与Aβ40的比值，14岁；磷酸化的Tau181，11岁；总Tau，10年；神经丝轻链，9岁；海马体积，8岁；认知能力下降，6年。随着认知障碍的进展，阿尔茨海默病组的脑脊液生物标志物水平的变化最初加速，然后减缓。

结论

在这项涉及散发性阿尔茨海默病临床诊断前20年的中国参与者的研究中，我们观察了脑脊液生物标记物的时间进程，诊断前它们与一组保持认知正常的参与者的生物标记物偏离的时间，以及生物标记物变得异常的时间顺序。（国家自然科学基金重点项目等资助；ClinicalTrials.gov号，NCT03653156.）

英文原文如下：

Abstracts

BACKGROUND  Biomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer's disease have not been extensively investigated in longitudinal studies.

METHODS  We conducted a multicenter, nested case-control study of Alzheimer's disease biomarkers in cognitively normal participants who were enrolled in the China Cognition and Aging Study from January 2000 through December 2020. A subgroup of these participants underwent testing of cerebrospinal fluid (CSF), cognitive assessments, and brain imaging at 2-year-to-3-year intervals. A total of 648 participants in whom Alzheimer's disease developed were matched with 648 participants who had normal cognition, and the temporal trajectories of CSF biochemical marker concentrations, cognitive testing, and imaging were analyzed in the two groups.

RESULTS  The median follow-up was 19.9 years (interquartile range, 19.5 to 20.2). CSF and imaging biomarkers in the Alzheimer's disease group diverged from those in the cognitively normal group at the following estimated number of years before diagnosis: amyloid-beta (Aβ)42, 18 years; the ratio of Aβ42 to Aβ40, 14 years; phosphorylated tau 181, 11 years; total tau, 10 years; neurofilament light chain, 9 years; hippocampal volume, 8 years; and cognitive decline, 6 years. As cognitive impairment progressed, the changes in CSF biomarker levels in the Alzheimer's disease group initially accelerated and then slowed.

CONCLUSIONS  In this study involving Chinese participants during the 20 years preceding clinical diagnosis of sporadic Alzheimer's disease, we observed the time courses of CSF biomarkers, the times before diagnosis at which they diverged from the biomarkers from a matched group of participants who remained cognitively normal, and the temporal order in which the biomarkers became abnormal. (Funded by the Key Project of the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03653156.).

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