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

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.

Risk factors for postoperative delirium following total hip or knee arthroplasty: A meta-analysis

“…After reading the titles and abstracts and excluding irrelevant literature, 45 articles were retained. After excluding duplicate studies and applying the inclusion criteria and exclusion criteria, 25 studies (Priner et al, 2008;Jankowski et al, 2011;Flink et al, 2012;Nandi et al, 2014;Chung et al, 2015;Wang et al, 2016Wang et al, , 2022Yen et al, 2016;Bosmak et al, 2017;Chen et al, 2017Chen et al, , 2021aCunningham et al, 2017Cunningham et al, , 2019Petersen et al, 2017;Aziz et al, 2018;Weinstein et al, 2018;Huang et al, 2019;Memtsoudis et al, 2019;Peng et al, 2019;He et al, 2020;Kijima et al, 2020;Qi et al, 2020;Jiang and Lei, 2022;Lin et al, 2022) including 3,767,761 patients from 9 countries were finally included. One study (Memtsoudis et al, 2019) separately reported the risk factors for delirium after TKA and THA.…”

Automated machine learning‐based model for the prediction of delirium in patients after surgery for degenerative spinal disease

“…Researchers have conducted a number of clinical studies to identify biomarkers accurately predicting PODs, such as the evaluation of plasma tau, 31 the S‐100β protein, 32 amyloid, 33 adiponectin 34 levels, and the level of PGRN in the cerebrospinal fluid. 35 Researchers are also trying to determine how to reduce the prevalence of the condition. Although POD can be predicted relatively well by these biomarkers, due to the complex sampling methods required and high associated costs, they are difficult to use in the clinical setting.…”

Potential Value of Serum Uric Acid in the Identification of Postoperative Delirium in Geriatric Patients Undergoing Knee Replacement

“…Data for this study were obtained from voluntary participants in the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study between January 2020 and May 2021 (Deng et al, 2022 ), and the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study between November 2020 and December 2021 (Lin et al, 2021 ; Wang et al, 2021 ).…”