Purpose:We aimed to investigate the relevance of body mass index (BMI) to postoperative delirium (POD), and to test whether the influences of BMI on POD were mediated by cerebrospinal fluid (CSF) biomarkers.Patients and methods: Our study recruited 682 and 761 cognitively intact individuals from the perioperative neurocognitive disorder risk factor and prognosis (PNDRFAP) study and the perioperative neurocognitive disorder and biomarker lifestyle (PND-ABLE) study, respectively. The incidence of POD was evaluated by using Confusion Assessment Method (CAM), and POD severity was measured by using the Memorial Delirium Assessment Scale (MDAS). Logistic regression was used to analyze the relationship between BMI and POD. The levels of Aβ40, Aβ42, T-tau, and P-tau in preoperative CSF were measured by enzyme-linked immune-sorbent assay (ELISA) in the PND-ABLE study. Mediation analysis with 5000 bootstrapped iterations was used to explore the mediation effects. Results:In the PNDRFAP study, the incidence of POD was 16.3%, with logistic regression analysis showing that BMI (odds ratio [OR] = 0.900, 95% confidence interval [CI] 0.823-0.985, p = .022) is a protective factor of POD. In the PNDABLE study, the incidence of POD was 18.7%, and regression analysis confirmed that BMI (OR = 0.832, 95% CI 0.761-0.910, p < .001) is a protective factor of POD, while T-tau (OR = 1.005, 95% CI 1.003-1.006, p < .001) and P-tau (OR = 1.037, 95% CI 1.024-1.050, p < .001) were risk factors of POD. Mediation analyses revealed that the association between BMI and POD was partially mediated by T-tau (proportion: 36%) and P-tau (proportion: 24%). Conclusion:Higher BMI mediated protective effects on POD through CSF biomarkers (T-tau and P-tau).

Several frequent polymorphisms in the CYP11B2 gene are suggested to be associated with essential hypertension and aldosterone secretion. In this study, we investigated the association of polymorphisms in CYP11B2 and CYP11B1 genes with the risk of primary hyperaldosteronism (PH). Three polymorphisms in the CYP11B2 gene (intron 2 conversion, rs1799998 and rs4539) and two polymorphisms in the CYP11B1 gene (rs6410 and rs6387) were analyzed in patients with PH and in the normal population. The rs6410 allelic frequencies in patients with aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were significantly different from those in controls at P¼1.09Â10 À5 and 0.015, respectively. There was a relative excess of AA homozygotes and AG heterozygotes of the rs6410 allele in the APA group as compared with the control group (P¼2.19Â10 À4 ). There were significantly different genotypes, AA and AG, of the rs6410 allele between the patients with IHA and the controls only after adjustments for age, gender and body mass index (odds ratio (OR)¼4.06, 95% confidence interval (CI) 1.31-12.66; OR¼2.41, 95% CI 1.02-5.72). One susceptible haplotype, AAAWT, was identified to be significantly associated with APA (OR¼1.44, 95% CI 1.19-1.76), and three susceptible haplotypes, AAAWT, AGGWT and AGAWC, were identified to be significantly associated with IHA (OR¼1.55, 95% CI 1.23-1.96; OR¼1.49, 95% CI 1.17-1.89; OR¼1.40, 95% CI 1.04-1.88). In contrast, one protective haplotype, GGAWT, showed a significant difference between the patients with APA and controls (OR¼0.73, 95% CI 0.55-0.97). Several haplotypes were associated with ARR in both the controls and cases. Our data demonstrated that there was a significant association between polymorphisms in the CYP11B2 and CYP11B1 genes and a genetic predisposition to PH. The association with IHA seemed closer compared with APA.

Objective: The aim of this study was to investigate whether progranulin (PGRN) levels in cerebrospinal fluid (CSF) were associated with postoperative delirium (POD) in geriatric patients undergoing knee replacement.Method: A total of 600 Han Chinese patients aged 65–90 years and who underwent unilateral total knee arthroplasty were included in the Perioperative Neurocognitive Disorder And Biomarker LifestylE (PNDABLE) study from June 2020 to November 2020. All participants were assessed using the Confusion Assessment Method and the Memorial Delirium Assessment Scale on postoperative days 1–7 (or before discharge) by an anesthesiologist. CSF PGRN and CSF biomarkers of POD were measured by ELISA. We analyzed the risk and protective factors of POD using the multivariate logistic regression, and the associations between CSF PGRN and CSF biomarkers of POD using multiple linear regression. We also explored whether the influence of CSF PGRN on POD was mediated by POD core pathology in linear regression models.Results: Postoperative delirium incidence was 9.7% (53/545). There were significant differences in preoperative CSF PGRN between patients with POD and non-POD (NPOD). As for CSF biomarkers, CSF Aβ40, T-tau, and P-tau were risk factors for POD, while CSF PGRN, Aβ42, and Aβ42/Aβ40 were protective factors for POD, as shown by the multivariate logistic regression analysis. CSF PGRN was positively associated with CSF Aβ42 and was negatively associated with CSF Aβ40, T-tau, and P-tau in patients with POD. We found that the AUC was 0.795 (95% CI = 0.706, 0.867) for PGRN between POD and NPOD groups. We found the influence of CSF PGRN on POD was mediated by POD core pathology. The effect was considered partial mediation with the proportion of mediation varying from 44.92 to 62.07%.Conclusion: Cerebrospinal fluid PGRN may be a reasonably good prognostic factor for POD development. Overall, amyloid pathology and tau protein might partially mediate the influence of PGRN on POD.Clinical Trial Registration:www.clinicaltrials.gov, identifier ChiCTR2000033439.

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