Potential Value of Cerebrospinal Fluid Progranulin in the Identification of Postoperative Delirium in Geriatrics Patients Undergoing Knee Replacement: The Perioperative Neurocognitive Disorder and Biomarker LifestylE Study.

Bin Wang,Xiujie Sun,Rui Dong,Xiyuan Deng,Yanan Lin,Fanghao Liu,Xu Lin,Jiahan Wang,Yanlin Bi

doi:10.3389/fnagi.2021.772795

Abstract

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.

Highlights

Postoperative delirium (POD) represents a serious complication following anesthesia and surgical procedures for patients undergoing surgical intervention (Safavynia and Goldstein, 2018)
We excluded 25 participants who had no information about Mini-Mental State Examination (MMSE), 5 participants without available cerebrospinal fluid (CSF) PGRN data, 17 participants who had no CSF biomarker data or had data outside four SDs of the mean, and 8 participants whose surgeries were suspended
We found that patients in the POD group had higher Memorial Delirium Assessment Scale (MDAS) scores than the NPOD group

Summary

Introduction

Postoperative delirium (POD) represents a serious complication following anesthesia and surgical procedures for patients undergoing surgical intervention (Safavynia and Goldstein, 2018). Postoperative delirium can lead to increased mortality, prolonged hospitalization, other complications such as Alzheimer’s disease (AD), and higher treatment costs (Steinmetz et al, 2009). Despite the prevalence and clinical importance of POD, its mechanisms are still poorly understood and no reliable biomarkers have been reported in previous studies. Studies have shown that PGRN in microglia cells may play an important role in brain injury, neuroinflammation, and neurodegeneration (Martens et al, 2012; Feng et al, 2020). Some studies have found that PGRN protein is closely related to changes in cognitive function (Suárez-Calvet et al, 2018)

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