老年手术患者与匹配非手术对照者的认知和脑脊液阿尔茨海默病相关生物标志物轨迹。
Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.
机构信息
Department of Anesthesiology, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina.
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.
出版信息
Anesthesiology. 2024 May 1;140(5):963-978. doi: 10.1097/ALN.0000000000004924.
BACKGROUND
Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults.
METHODS
The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid β (Aβ) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls.
RESULTS
The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aβ, tau, or p-tau levels, or tau/Aβ or p-tau/Aβ ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (β, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up.
CONCLUSIONS
During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aβ) changes or greater cognitive decline.
背景
麻醉和/或手术会加速阿尔茨海默病的病理进程，并导致动物模型出现记忆缺陷，但目前缺乏前瞻性数据来比较接受手术和未接受手术的老年患者的脑脊液（CSF）阿尔茨海默病相关生物标志物和认知轨迹。因此，本研究旨在更好地了解麻醉和/或手术是否会导致老年患者认知能力下降或加速与阿尔茨海默病相关的病理进程。
方法
作者通过基于年龄、性别和受教育年限的分层匹配，共纳入了 140 名 60 岁或以上接受非神经外科大手术的患者和 51 名非手术对照组患者。在手术前、手术后 24 小时和 6 周，以及对照组的同期，测量了 CSF 中的淀粉样蛋白β（Aβ）42、tau 和 p-tau-181p 水平和认知功能。
结果
两组在 31 项基线特征中的 25 项上匹配良好。组间或组间与时间的交互作用对基线至术后 24 小时或 6 周的 CSF Aβ、tau 或 p-tau 水平或 tau/Aβ 或 p-tau/Aβ 比值均无影响（所有 Bonferroni P 值>0.05），且两组在 1 年内的这些 CSF 标志物也无差异（所有 P 值>0.05）。非手术对照组在基线认知方面与手术组无差异（平均差异，0.19[95%CI，-0.06 至 0.43]；P=0.132），但在 1 年后的认知能力下降程度大于手术组（β，-0.31[95%CI，-0.45 至 -0.17]；P<0.001），即使在控制两组之间的基线差异后也是如此。然而，在使用认知数据的缺失值插补或逆概率加权来校正失随访的情况下，在 1 年术后认知变化的模型中，非手术组和手术组之间的差异无统计学意义。
结论
在 1 年的时间内，与匹配的非手术对照组相比，该研究未发现接受麻醉和非心脏、非神经外科手术的老年患者有加速 CSF 阿尔茨海默病相关生物标志物（tau、p-tau 和 Aβ）变化或认知能力下降的证据。
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