Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study

Ballweg, Tyler; White, Marissa; Parker, Margaret; Casey, Cameron; Bo, Amber Y.; Farahbakhsh, Zahra; Kayser, Austin; Blair, Alexander; Lindroth, Heidi; Pearce, Robert A.; Blennow, Kaj; Zetterberg, Henrik; Lennertz, Richard; Sanders, Robert D.

doi:10.1016/j.bja.2020.08.061

Cited by 84 publications

(87 citation statements)

References 22 publications

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“…Another important source of IL-1β in CNS was astrocytes. It is reported that GFAP concentrations showed no relationship to postoperative delirium [72], which is coincidence with our results. During neuroin ammation, astrocytes undergo morphological changes that are not strictly dependent on GFAP protein level [73] and only 15% of astrocytes stain for GFAP in the mouse brain [74], thus the role of astrocytes in POCD needs to be determined by further experiments.…”

Section: Discussionsupporting

confidence: 92%

The Expression of Interleukin-1β Is Regulated by DNA Methylation in Microglia of Hippocampus to Participate Postoperative Cognitive Dysfunction in Aged Mice

Gao

Yang

Xiao

et al. 2021

Preprint

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BackgroundPostoperative cognitive dysfunction (POCD) is one of the common postoperative complications in the elderly. The main clinical manifestation is memory impairment, which can cause permanent damage and even dementia in severe cases. However, the pathogenesis of POCD is still unknown. Age and neuroinflammation are known to be closely related to its occurrence, while DNA methylation is very important for transcriptional silencing and neuroinflammation. Consequently, this study intended to establish a mouse model of POCD to explore the role of DNA methylation in regulating the expression of interleukin-1β which participated POCD in aged mice.MethodsPOCD model was established by exploratory laparotomy and evaluated by new object experiment and Y maze test. In addition, ELISA, RT-PCR, Western blotting, immunofluorescence, microglia isolation and flow cytometry methods were used to detect the inflammatory state of dorsal hippocampal after surgery. Moreover, MSP, MeDIP and IL-1β promoter DNA methylation sequencing were used to explore the regulation of DNA methylation on IL-1β in this model. Finally, Golgi staining and Western blotting were used to further explore the role of IL-1β in POCD and its possible mechanisms. ResultsCognitive impairment was observed in aged but not adult mice at 1 day after surgery. There was a significant correlation between the level of IL-1β in dorsal hippocampus and the performance of cognitive function. The microglia in the dorsal hippocampus was activated and the IL-1β promoter DNA methylation was decreased in the aged mice. The increased expression of IL-1β impaired synaptic plasticity and hippocampus-dependent memory formation. Intracerebroventricular administration of IL-1β receptor antagonist could prevent the cognitive impairment of aged mice after surgery, reverse the decrease of dendritic spine density and synapse-associated protein expression induced by surgery.ConclusionDNA methylation regulation may be an important mechanism for greater susceptibility to POCD in aged mice by regulating the expression of IL-1β. IL-1β inhibiting prevented surgery-induced cognitive decline and synaptic plasticity dysfunction. The research also provided a new target for the clinical prevention of the occurrence of POCD in the elderly.

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Section: Discussionsupporting

confidence: 92%

The Expression of Interleukin-1β Is Regulated by DNA Methylation in Microglia of Hippocampus to Participate Postoperative Cognitive Dysfunction in Aged Mice

Gao

Yang

Xiao

et al. 2021

Preprint

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“…The authors suggested that elevated tau protein could indicate synaptic pruning of tau containing synpases. 16 The significantly greater increase in T-tau as compared to NFL in our own study supports the hypothesis that the presence of tau and NFL in blood plasma could reflect different processes.…”

Section: Discussionsupporting

confidence: 85%

“… 15 A further analysis of the same cohort indicated that elevated postoperative T-tau was also associated with POD. 16 In this second analysis, recovery from delirium was associated with return of T-tau to baseline values whilst NFL continued to rise until day 4 postoperatively. The authors concluded that whilst NFL is likely a marker of neuronal injury, tau protein may indicate more subtle changes in the central nervous system.…”

Section: Discussionmentioning

confidence: 77%

Comparing the effect of xenon and sevoflurane anesthesia on postoperative neural injury biomarkers: a randomized controlled trial

et al. 2022

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General anesthesia and surgery are associated with an increase in neural injury biomarkers. Elevations of these neural injury biomarkers in the perioperative period are associated with postoperative delirium. Xenon has been shown to be protective against a range of neurological insults in animal models. It remains to be seen if xenon anesthesia is neuroprotective in the perioperative setting in humans. Twenty-four participants scheduled for lithotripsy were randomized to receive either xenon or sevoflurane general anesthesia. There was no statistically significant difference in the concentrations of postoperative neural injury biomarkers between the xenon and sevoflurane group. Following the procedure there was a significant increase in the concentration from baseline of all three biomarkers at 1 hour post-induction with a return to baseline at 5 hours. General anesthesia for lithotripsy was associated with a significant increase at 1 hour post-induction in the neural injury biomarkers total tau, neurofilament light and tau phosphorylated at threonine 181, a marker of tau phosphorylation. The protocol was approved by the St. Vincent’s Hospital Melbourne Ethics Committee (approval No. HREC/18/SVHM/221) on July 20, 2018 and was registered with the Australia New Zealand Clinical Trials Registry (registration No. ACTRN12618000916246) on May 31, 2018.

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“…Tomaszewski D [49] con rmed that the decrease in rSctO 2 readings may be due to micro-thromboembolic events in patients after total hip arthroplasty and S100B may be a more speci c marker of astroglial damage. Tyler Ballweg [50] reported that the change in perioperative neuronal injury biomarker tau was associated with delirium incidence and severity. We observed the relation between surgery procedure and rScto 2 score in different time point.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Decreases of regional cerebral oxygen saturation reading during hip arthroplasty associated with postoperative delirium in older adults

Zhou

Wang

et al. 2021

Preprint

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Background Postoperative delirium (POD) is a sign of deterioration in the homeostasis and physical status of the patient. However, there have been no reports regarding the relationship between the decrease of regional cerebral oxygen saturation (rSctO2) reading during surgery and the POD in hip replacement in the elder. This study aims to investigate this correlation and the incidence of POD.Methods We performed a retrospective study of 4834 patients who underwent hip arthroplasties between 2015 and 2019 at our hospital. Data were collected as part of routine patient care. The patients’ cognitive performance was evaluated by using the Manual of Mental Disorders (DSM-IV-TR 4th edition) criteria. Patients found to be delirious after surgery served as the delirium group, other patients who did not develop delirium after surgery regarded as the no-delirium group. The various factors including the decline of rSctO2 reading intraoperatively were assessed using Multivariable logistic regression models. Odds ratio (OR) and 95% confidence intervals (CI) are reported.Results POD was found in 27 patients (n=351); the incidence of POD was 7.7%; all of them were in their 70’s or 80’s. Lab data and rSctO2 reading before surgery were no significantly difference between the delirium group and the no-delirium group. Patients who displayed the decline of rSctO2 reading intraoperatively were at higher risk for POD (compared with no-delirium patients: OR2.169 CI 1.663-2.829 p=0.000) and gender (compared with no-delirium patients: OR 0.163 CI 0.029-0.909 p=0.039) was at a higher risk. Twenty-four patients recovered from POD gradually. One patient had persistent and severe cognitive dysfunction after surgery, two patients died of complications either acute pulmonary embolism 4 days after surgery or acute stroke 21 days after surgery respectively.Conclusions The incidence of POD was 7.7%. This study shows that the decline of rSctO2 reading during hip replacement surgery in the elder is associated with increased probability for the POD.

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Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study

Cited by 84 publications

References 22 publications

The Expression of Interleukin-1β Is Regulated by DNA Methylation in Microglia of Hippocampus to Participate Postoperative Cognitive Dysfunction in Aged Mice

The Expression of Interleukin-1β Is Regulated by DNA Methylation in Microglia of Hippocampus to Participate Postoperative Cognitive Dysfunction in Aged Mice

Comparing the effect of xenon and sevoflurane anesthesia on postoperative neural injury biomarkers: a randomized controlled trial

WITHDRAWN: Decreases of regional cerebral oxygen saturation reading during hip arthroplasty associated with postoperative delirium in older adults

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