Relationship Between Preoperative Neutrophil-to-lymphocyte Ratio and Postoperative Delirium: The PNDABLE and the PNDRFAP Cohort Studies

Objectives: In this study, the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and Alzheimer-related biomarkers in cerebrospinal fluid (CSF) was investigated to determine whether high NLR is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy.

Methods: We selected 1000 patients from the perioperative neurocognitive disorder risk factor and prognosis (PNDRFAP) database and 999 patients from the perioperative neurocognitive disorder and biomarker lifestyle (PNDABLE) database. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aβ , Aβ , P-tau, and tau protein). Mini-mental state examination was used to assess the preoperative mental status of patients. POD was diagnosed using the confusion assessment method and assessed for severity using the memorial delirium assessment scale. Logistic regression analysis was utilized to explore the association of preoperative NLR with POD. What's more, we also performed sensitivity analysis by adding corrected confounders, and the results were almost unchanged. Spearman's rank correlation was used to determine the associations between NLR and Alzheimer-related biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we use decision curves and the nomogram model to evaluate the efficacy of preoperative NLR in predicting POD; we also performed external validation using data from Qilu Hospital.

Result: Logistic regression results showed that an elevated preoperative NLR was a risk factor for the development of POD in patients (PNDRFAP: OR = 1.067, 95% CI 1.020-1.116; PNDABLE: OR = 1.182, 95% CI 1.048-1.335, p < .05). Spearman's rank correlation analysis showed a positive but weak correlation between NLR and P-tau/T-tau (R = .065). The mediating effect results indicate that NLR likely mediates the occurrence of POD through elevated tau protein levels (proportion: 47.47%). The results of the box plots showed statistically significant NLR and CSF biomarkers between the POD and non-POD (NPOD) groups (p < .05), with higher NLR, P-tau, and T-tau in the POD group than in the NPOD group. In contrast, the NPOD group had higher Aβ levels compared to the POD group. In addition, we used R package to plot the decision curve and nomogram both suggesting a good predictive effect of preoperative NLR on the occurrence of POD.

Conclusion: Elevated preoperative NLR levels may be a risk factor for POD and likely mediate the development of POD through elevated P-tau/T-tau levels.