ABSTRACT
Objectives: The relationship between preoperative serum uric acid (SUA) and cerebrospinal fluid (CSF) Alzheimer-related biomarkers were investigated to determine whether high SUA is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy. Methods: The participants were selected from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study and the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study. The logistic regression equation was used to analyze the risk factors and protective factors of POD. The interaction term (SUA × Sex) was introduced into the linear model to explore the potential modification effects of sex on the identified correlations. We analyzed the mediating effects of Alzheimer-related biomarkers. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of SUA and Alzheimer-related biomarkers in predicting POD. Results: Patients with POD had elevated SUA level (PNDRFAP: p = 0.002, PNDABLE: p < 0.001). Preoperative SUA level was positively correlated with CSF phosphorylated tau (P-tau) (p = 0.027) and ß-amyloid42 (Aß42)/P-tau (p = 0.023). Interaction analysis did not find any modification effect of sex. The relationship between SUA and POD was partially mediated by CSF P-tau (15.3%). ROC curve showed that the model combining SUA and Alzheimer-related biomarkers had better performance in predicting POD [area under the curve (AUC) = 0.880; p < 0.001], and the predictive model is accurate. Conclusions: High SUA may enhance CSF P-tau level, thus increasing the risk of POD, and the model combining SUA and Alzheimer-related biomarkers can accurately predict the occurrence of POD.
ABSTRACT
Objective: We aimed to investigate the relationship between Framingham Heart Study general cardiovascular disease risk score (FHS-CVD risk score) and postoperative delirium (POD) among patients who had unilateral total knee arthroplasty performed under epidural anesthesia. Furthermore, we examined whether such a hypothesized relationship was mediated by the cerebrospinal fluid (CSF) biomarkers. Methods: A total of 750 participants were included in the current study. And the data were drawn from the database obtained from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study. The preoperative cognitive function of participants was measured by using Mini-Mental State Examination (MMSE). The incidence of POD was assessed using the Confusion Assessment Method (CAM). The POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). The POD CSF biomarkers included in the current study were: Aß42, T-tau, P-tau, Aß42/T-tau, and Aß42/P-tau. The level of the CSF biomarkers was measured using the enzyme-linked immune-sorbent assay (ELISA) in the PNDABLE study. Linear regression analysis was performed to examine the relationship between the FHS-CVD risk score and the POD CSF biomarkers. Logistic regression was used to analyze the relationship between FHS-CVD risk score, POD CSF biomarkers, and POD incidence. The proposed mediating effect of CSF biomarkers was evaluated using Mediation Analysis with 10,000 bootstrapped iterations. The receiver operating characteristic (ROC) curve is chosen as the evaluation metric for assessing the efficacy of the FHS-CVD risk score in predicting POD. Results: In the PNDABLE study, the overall incidence of POD was 22.9% with 37.2% in the higher vascular risk group and 7.9% in the lower vascular risk group. Multiple linear regression models showed that a higher preoperative FHS-CVD risk score was positively correlated with CSF T-tau (ß = 0.218, P = 0.015) and P-tau level (ß = 0.309, P < 0.001) in the higher vascular risk group. After adjusting for age (40-90 years), gender, education, MMSE, smoking history, drinking history, hypertension, diabetes, and the presence of CHD (cardiovascular heart disease), the results of the logistic regression analysis demonstrated the effect of Aß42 (OR = 0.994, 95% CI 0.992-0.996, P < 0.001), Aß42/T-tau (OR = 0.353, 95% CI 0.254-0.491, P < 0.001), and Aß42/P-tau (OR = 0.744, 95% CI 0.684-0.809, P < 0.001) in protecting patients against POD. However, the FHS-CVD risk score (OR = 1.142, 95% CI 1.017-1.282, P = 0.025) and the remaining two biomarkers: T-tau (OR = 1.005, 95% CI 1.004-1.007, P < 0.001) and P-tau (OR = 1.045, 95%CI 1.029-1.062, P < 0.001) were identified as the risk factors. Mediation analyses revealed that the association between FHS-CVD risk score and POD was partially mediated by T-tau (proportion: 31.6%) and P-tau (proportion: 23.6%). The predictive power of the FHS-CVD risk score was validated by the ROC curve with an AUC of 0.7364. Conclusion: Higher vascular risk score is one of the preoperative risk factors for POD, which is partly mediated by CSF biomarker tau protein. Clinical Trial Registration: [www.clinicaltrials.gov], identifier [ChiCTR2000033439].
ABSTRACT
Background: Although it has been proven that social networks are related to cognition, studies are conducted to characterize the correlation between social networks and postoperative delirium (POD). Objective: We investigated whether suboptimal social networks are a risk factor for POD, and to verify whether different levels of intimacy in the same social relationship can affect the concentration of cerebrospinal fluid (CSF) biomarkers, such as amyloid-ß (Aß42), total tau (T-tau), and phosphorylated tau (P-tau), and the mediating role of CSF biomarkers between social network and POD in middle-aged and elderly Han people. Methods: Our study recruited 743 participants from The Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study. Confusion Assessment Method (CAM) was used to evaluate the incidence of POD and its severity was measured using the Memorial Delirium Assessment Scale (MDAS). The social networks were measured using self-reported questionnaires about social ties. Mann-Whitney U test, Logistic Regression and Independent-samples test were used for Statistical Analysis. Results: The incidence of POD was 20.7%. Mann-Whitney U test showed that the total score of the social network was associated with POD (P < 0.001). Independent-samples test showed that different levels of intimacy in the same social relationship were significantly associated with CSF POD biomarkers, and mediation analyses revealed that the association between suboptimal social networks and POD was partially mediated by T-tau (proportion: 20%), P-tau (proportion: 33%), Aß42/T-tau (proportion: 14%), and Aß42/P-tau (proportion: 15%). Conclusion: Having suboptimal social networks is a risk factor for POD in middle-aged and elderly Han people. CSF POD biomarkers can mediate the correlation between suboptimal social networks and POD, which is mainly mediated by tau protein. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2000033439.
