与非载脂蛋白 E4 携带者相比，老年载脂蛋白 E4 携带者的围手术期神经认知和功能神经影像学轨迹：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.
机构信息
Department of Psychiatry and Behavioural Medicine, Division of Behavioural Medicine & Neurosciences, Duke University Medical Centre, Durham, NC, USA; Centre for Cognitive Neuroscience, Duke University, Durham, NC, USA; Duke Brain Imaging and Analysis Centre, Durham, NC, USA; Duke Institute for Brain Sciences, Durham, NC, USA.
Department of Anaesthesiology, Duke University Medical Centre, Durham, NC, USA.
出版信息
Br J Anaesth. 2021 Dec;127(6):917-928. doi: 10.1016/j.bja.2021.08.012. Epub 2021 Sep 14.
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 [65] vs 378 pg ml [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=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=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.
背景
手术后认知功能障碍是老年人的一个主要问题。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 名年龄在 60 岁以上、接受全身麻醉下非心脏手术的讲英语的患者，其中 52 名患者接受了神经影像学检查。我们在手术前和手术后 6 周测量了认知功能、CSF 中的 Aβ、tau 和 p-tau 水平以及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（术前中位数 CSF Aβ[中位数绝对偏差]，APOE4 为 305pg/ml[65]与 378pg/ml[38]；P=0.001）外，APOE4 与认知或 CSF 生物标志物无显著相关性。控制年龄后，APOE4 携带者的几个与阿尔茨海默病相关的脑区之间的术前功能连接明显大于非携带者，包括左后扣带回皮质和左角回之间（β[95%置信区间，CI]，0.218[0.137-0.230]；P=0.016）。APOE4 携带者但非非携带者在手术后 6 周内从几个脑区的功能连接减少，包括左后扣带回皮质和左角回之间（β[95%CI]，-0.196[-0.256 至-0.136]；P=0.001）。控制术前 CSF Aβ 水平后，大多数术前和术后功能连接差异没有改变。
结论
社区居住的 APOE4 携带者和非携带者的认知和 CSF Aβ、tau 或 p-tau 水平的术后变化轨迹没有差异。APOE4 携带者表现出更大的术前功能连接和更大的术后关键阿尔茨海默病风险区域的功能连接减少，这是通过 Aβ 非依赖性机制发生的。
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