Data_Sheet_2_Subjective cognitive decline may mediate the occurrence of postoperative delirium by P-tau undergoing total hip replacement: The PNDABLE study.docx

ObjectiveWe again investigated the relationship between subjective cognitive decline (SCD) and postoperative delirium (POD) with a larger sample queue. We also determined whether SCD could cause the occurrence of POD through cerebrospinal fluid (CSF) biomarkers.MethodsA prospective, observational cohort study was implemented in the Qingdao Municipal Hospital Affiliated with Qingdao University. This study recruited 1,471 qualified patients affiliated with the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study scheduled for total hip replacement under combined spinal and epidural anesthesia from June 2020 to May 2022. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were used to assess the cognitive level of the patients the day before surgery. Pittsburgh sleeps quality index (PSQI) scale was used to assess sleep status. Patients were divided into the SCD group and the non-SCD (NSCD) group based on the Subjective Cognitive Decline Scale (SCDS). CSF was collected after a successful spinal-epidural combined puncture, and amyloid-β40 (Aβ40), amyloid-β42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-Tau) in CSF were analyzed by enzyme-linked immunosorbent assays. After the surgery, the incidence of POD was determined by the Confusion Assessment Scale (CAM), and Memorial Delirium Assessment Scale (MDAS) score was used to determine the severity of POD. Logistic regression and sensitivity analyses were performed to determine the relationship between CSF biomarkers, SCD, and POD. The mediating effect was used to analyze the function of specific CSF biomarkers in the relationship between SCD and POD. The risk factors of SCD were also separately verified by logistic regression and sensitivity analysis models.ResultsThe total incidence rate of POD was 19.60% (n = 225/1148), which was 29.3% (n = 120/409) in the SCD group and 14.2% (n = 105/739) in the NSCD group. We comprehensively considered the effect of covariates such as age, hypertension, and diabetes. Multivariate logistic regression analysis showed that SCD (OR = 1.467, 95%CI: 1.015–2.120, p = 0.042) and P-tau (OR = 1.046, 95%CI: 1.028–1.063, p −2, p ConclusionPatients with SCD are more likely to develop POD undergoing total hip replacement, and SCD can mediate the occurrence of POD via P-tau.Clinical trial registrationThis study was registered at China Clinical Trial Registry (Chictr2000033439).</p

Data_Sheet_1_Subjective cognitive decline may mediate the occurrence of postoperative delirium by P-tau undergoing total hip replacement: The PNDABLE study.xlsx

ObjectiveWe again investigated the relationship between subjective cognitive decline (SCD) and postoperative delirium (POD) with a larger sample queue. We also determined whether SCD could cause the occurrence of POD through cerebrospinal fluid (CSF) biomarkers.MethodsA prospective, observational cohort study was implemented in the Qingdao Municipal Hospital Affiliated with Qingdao University. This study recruited 1,471 qualified patients affiliated with the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study scheduled for total hip replacement under combined spinal and epidural anesthesia from June 2020 to May 2022. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were used to assess the cognitive level of the patients the day before surgery. Pittsburgh sleeps quality index (PSQI) scale was used to assess sleep status. Patients were divided into the SCD group and the non-SCD (NSCD) group based on the Subjective Cognitive Decline Scale (SCDS). CSF was collected after a successful spinal-epidural combined puncture, and amyloid-β40 (Aβ40), amyloid-β42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-Tau) in CSF were analyzed by enzyme-linked immunosorbent assays. After the surgery, the incidence of POD was determined by the Confusion Assessment Scale (CAM), and Memorial Delirium Assessment Scale (MDAS) score was used to determine the severity of POD. Logistic regression and sensitivity analyses were performed to determine the relationship between CSF biomarkers, SCD, and POD. The mediating effect was used to analyze the function of specific CSF biomarkers in the relationship between SCD and POD. The risk factors of SCD were also separately verified by logistic regression and sensitivity analysis models.ResultsThe total incidence rate of POD was 19.60% (n = 225/1148), which was 29.3% (n = 120/409) in the SCD group and 14.2% (n = 105/739) in the NSCD group. We comprehensively considered the effect of covariates such as age, hypertension, and diabetes. Multivariate logistic regression analysis showed that SCD (OR = 1.467, 95%CI: 1.015–2.120, p = 0.042) and P-tau (OR = 1.046, 95%CI: 1.028–1.063, p −2, p ConclusionPatients with SCD are more likely to develop POD undergoing total hip replacement, and SCD can mediate the occurrence of POD via P-tau.Clinical trial registrationThis study was registered at China Clinical Trial Registry (Chictr2000033439).</p

Expression of chop in hippocampus CA1.

<p>(a) Immunohistochemistry showed the chop was barely detected in sham group (A).The expression of chop in hypothermia group (B) is much weaker than that in ischemia group (C) at reperfusion 24 hours. /400×visual field (b) Western blot analysis showed that the chop was barely detected in sham group. In brains of ischemia group, it was increased 6 hour after 15 minutes of ischemia and gradually decreased thereafter; however, the degree of increase was much smaller in the hypothermia brains. (c) Quantitative analysis of Western blotting showed that hypothermia after ischemia significantly decreased chop after 15 minutes of ischemia (P<0.05 compared with ischemia brains at the same time points. 6 rats from each group at every time points were used for analysis).</p

Neurons in hippocampus CA1 area.

<p>(a) The picture showed the neurons in hippocampus CA1 area. The neurons in sham group (A) displayed regular appearance with large and round nuclei but pyknosis was observed in ischemia (C) and hypothermia group (B). (b) Compared with sham group(89.3±6.1) (A), the number of normal neuronal is fewer and the neurons of morphologic abnormality is more in ischemia group(47.3±4.5) (C). The number of survival neurons in hypothermia group(64.5±7.5) (B) is more than that in ischemia group. /400×visual field.</p

Neuronal apoptosis in CA1 region of hippocampus induced by global cerebral ischemia.

<p>Detection of apoptosis in hippocampus CA1 pyramidal neurons was carried out using Tunel staing. The sham group showed a large number of neurons and almost no TUNEL-positive cells (5.1±1.2) (A). In ischemia (C) and hypothermia (B) groups, the number of neurons were decreased and substantial TUNEL-positive cells were detected. The number of TUNEL-positive cells in hypothermia group (34.4±4.2) (B) is more than in ischemia group (40.5±5.7) (C), /400×visual field.</p

Data_Sheet_1_The relationship between mild cognitive impairment and postoperative delirium undergoing total knee arthroplasty: The PNDABLE study.doc

BackgroundPatients undergoing surgery are at a higher risk of developing postoperative delirium (POD) as a result of anesthesia and surgical procedures. This study examined the association between POD and mild cognitive impairment (MCI) and whether MCI influences POD through the core pathology of POD.MethodsWe enrolled Chinese Han patients undergoing unilateral total knee arthroplasty (aged 50–90, weighing 50–80 kg, and using ASAI-II), combined with epidural anesthesia between October 2020 and June 2021. All the participants were assessed using Winblad's criteria for diagnosing MCI on pre-operation and using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale (MDAS) postoperative 1–7 days (or before discharge) for diagnosing POD by an anesthesiologist. Cerebrospinal fluid (CSF) biomarkers of POD were measured by enzyme-linked immunosorbent assay (ELISA). To examine the mechanism by which POD pathologies affect cognition, causal mediation analyses were performed.ResultsPOD incidence was 20.2%, including 32.5% in the MCI group and 12.4% in the non-mild cognitive impairment (NMCI) group. The MCI and CSF levels of T-tau and P-tau were risk factors, and the CSF levels of Aβ42, Aβ42/ T-tau, and Aβ42/ P-tau were protective factors in POD (p ConclusionMCI may be a reasonably good prognostic factor in POD development. Overall, amyloid pathology and tau protein might partially mediate the influence of MCI on POD.Clinical trial registrationwww.clinicaltrials.gov, identifier: ChiCTR2000033439.</p