Background

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.

Methods

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.

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]; P_FWE=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]; P_FWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels.

Conclusions

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.

中文翻译：

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与非携带者相比，老年 APOE4 携带者的围手术期神经认知和功能神经影像学轨迹：一项前瞻性队列研究的二次分析

背景

手术后的认知功能障碍是老年人的主要问题。在这里，我们确定了APOE4对老年患者围手术期神经认知功能的影响。

方法

我们在一项观察性队列研究中招募了 140 名年龄≥60 岁且计划在全身麻醉下进行非心脏手术的讲英语的患者，其中 52 名接受了神经影像学检查。我们测量了认知；CSF 中的 Aβ、tau、p-tau 水平；术前和术后 6 周六个阿尔茨海默病风险区域的静息状态内在功能连接。

结果

除了APOE4携带者的 CSF Aβ 水平低于非携带者（术前 CSF Aβ 中位数 [中位绝对偏差]，APOE4 305 pg ml -1 ^[ 65] vs 378 pg ml ^-1 [38]，分别为；P =0.001）。控制年龄后，APOE4携带者在与阿尔茨海默病有关的几个大脑区域之间的术前功能连接性明显高于非携带者，包括左后扣带皮层和左角回之间（β [95% 置信区间，CI]，0.218 [0.137 –0.230]；P _FWE =0.016）。APOE4携带者，而非非携带者，从手术前到手术后 6 周，包括左后扣带皮层和左角回之间的几个大脑区域之间的连接性显着下降（β [95% CI]，–0.196 [–0.256 至 – 0.136]；P _FWE = 0.001)。大多数术前和术后功能连接差异在控制术前 CSF Aβ 水平后没有改变。

结论

认知和 CSF Aβ、tau 或 p-tau 水平的术后变化轨迹在社区居住的老年APOE4携带者和非携带者之间没有差异。APOE4携带者在关键的阿尔茨海默病风险区域显示出更好的术前功能连接和术后更大的功能连接减少，这是通过 Aβ 独立机制发生的。