【原】【经典文献阅读 】老年APOE4携带者与非携带者的围手术期神经认知功能神经成像轨迹：一项前瞻性队列研究的二次分析

Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study

老年APOE4携带者与非携带者的围手术期神经认知功能神经成像轨迹：一项前瞻性队列研究的二次分析

By丹妮&苗&猫

Abstract

backgroud

Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients.

术后认知功能障碍是老年人面临的一个主要问题。在这里，我们研究了APOE4对老年患者围手术期神经认知功能的影响

POCD这个概念仍可使用，但需准确定义时间范围 文中已经明确定义

Method

We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery.

在一项观察性队列研究中，我们招募了140名能说英语的＞60岁老年患者，他们计划在全身麻醉下进行非心脏手术。其中52例接受了神经影响检查。我们测量了他们的认知能力水平；脑脊液中的Aβ、tau、p-tau水平；从术前和至术后6周的6个阿尔茨海默病风险区域的静息态功能连接。

Results

There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml−1 [65] vs 378 pg ml−1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (β [95% confidence interval, CI], 0.218 [0.137–0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (β [95% CI], –0.196 [–0.256 to –0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels.

APOE4携带者的脑脊液Aβ水平低于非携带者（术前脑脊液Aβ[绝对中位差] 305 pgml−1[65] vs 378pgml-1[38])，认知水平或脑脊液生物标志物无显著差异。控制年龄后，在几个与阿尔茨海默病有关的脑区域中，包括左后扣带皮层和左角回之间([95%CI]，0.218[0.137–0.230]；PFWE=0.016)，APOE4携带者术前功能连接明显强于非携带者。APOE4携带者在术前至术后6周连接显著下([95%CI]-0.196[-0.256–-0.136]；PFWE=0.001)。控制术前脑脊液Aβ水平后，大多数患者术前和术后的功能连通性没有差异变化。

Conclusion

Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.

老年APOE4携带者和非携带者术后认知能力变化轨迹和脑脊液Aβ、tau或p-tau水平无关。在几个主要的阿兹海默病风险区域，APOE4携带者术前功能连接更强，术后功能连接显著降低，这仅通过Aβ机制发生的。

Figure&Table

队列研究

 定义 

将人群按是否暴露于某可疑因素及其暴露程度分为不同的亚组，追踪其各自的结局，比较不同亚组之间结局频率的变异，从而判定暴露因子与结局之间有无因果关联及关联大小的一种观察性研究

原理 

种类

特点

1.属于观察法

暴露因素不是人为给予的，在研究开始前已经客观存在

2.立对照组

可与暴露组来自一个人群，也可来自不同人群

3.由“因”及“果“

先知道其“因”，再纵向前瞻观察究其果

4.能明确暴露与疾病的因果联系

能切实知道研究对象的暴露状况以及结局发生，计算结局的发生率