CSF PGRN May be Associated With Postoperative Delirium After Knee Replacement in Elderly Patients: The PNDABLE Study

Abstract BackgroundPostoperative delirium (POD) represents a serious complication following anesthesia and surgical procedures for patients undergoing surgical intervention (1). Little is known about the mechanisms underlying similarities in the core features between postoperative delirium (POD) and progranulin (PGRN)-related cognitive disorders. We herein investigated the relationship between preoperative CSF PGRN concentration and POD occurrence in the Han Chinese patients undergoing unilateral total knee arthroplasty.MethodsWe conducted an observational, prospective, and 1:1 matched (on age older than 65, the unilateral total knee arthroplasty, American Society of Anesthesiologist’ (ASA) physical status, duration of surgery, and intraoperative bleeding) case-control study. POD cases and non-POD controls were selected from the overall cohort using Confusion Assessment Method (CAM). Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS). CSF PGRN and core biomarkers were measured by ELISA using the microplate reader. The associations of CSF PGRN levels with POD risk and CSF core biomarkers were assessed.ResultsPOD incidence was 9.7% (53/545). There were significant differences in preoperative CSF PGRN concentration between POD patients and controls (P<0.001), and CSF PGRN levels increased with age, as demonstrated by a significantly positive correlation (r=0.796, P<0.001).CSF PGRN levels to increase with CAM scores and MDAS scores, as demonstrated by significantly positive correlations (r=0.693, P<0.001; r=0.590, P<0.001). There were positive associations of CSF PGRN with T-tau (β = -0.501, P < 0.001) and P-tau (β = -0.470, P < 0.001) and negative associations of CSF PGRN with Aβ1–42 (β = -0.576, P < 0.001), Aβ1–40 (β = -0.488, P < 0.001), Aβ42/p-tau (β = -0.422, P < 0.001), and Aβ42 / T- tau (β = -0.395, P < 0.001) in POD patients. The ROC curve analysis of PGRN showed that PGRN concentrations had high diagnostic value for POD.ConclusionsCSF PGRN may be associated with the POD. Aβ pathology is associated with a decrease in CSF PGRN in the absence of tau deposition and neurodegeneration, whereas tau pathology and neurodegeneration is associated with an increase in CSF PGRN.Clinical Trial Registrationwww.clinicaltrials.gov, identifier ChiCTR2000033439.