Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery

Wiberg, Sebastian; Holmgaard, Frederik; Zetterberg, Henrik; Nilssøn, Jens; Kjærgaard, Jesper; Wanscher, Michael; Langkilde, Annika Reynberg; Hassager, Christian; Rasmussen, Lars S.; Blennow, Kaj; Vedel, A

doi:10.1053/j.jvca.2021.05.016

Cited by 28 publications

(30 citation statements)

References 37 publications

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“…Cardiac surgery patients may also experience cognitive-related post-surgical effects due to surgery-associated inflammation, peri-operative hypoperfusion, and free radicals creating a neurotoxic environment as evidenced by the peri-operative release of neurofilament light (NF-L) and protein S100 [ 10 , 11 , 12 , 13 ]. Furthermore, the persistence of local post-surgical neuroinflammation compounds neuronal damage and may lead to shrouded neurodegeneration as part of the chronic process of postoperative neurocognitive decline (POCD) [ 9 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…These markers were studied extensively during the acute period of cardiac surgery; however, there are fewer data reflecting their persistence during recovery [ 23 ]. Interestingly, an increase in non-classical cognitive decline was observed in the peri-operative period [ 5 , 15 , 16 , 17 , 19 , 23 , 24 , 32 , 33 ]. Concomitantly, peri-operative delirium, vascular dementia, Parkinson’s-like disease, and other representations of central nervous system (CNS) dysfunction are increasingly recognized as cardiac surgery complications [ 9 , 16 , 17 , 18 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, an increase in non-classical cognitive decline was observed in the peri-operative period [ 5 , 15 , 16 , 17 , 19 , 23 , 24 , 32 , 33 ]. Concomitantly, peri-operative delirium, vascular dementia, Parkinson’s-like disease, and other representations of central nervous system (CNS) dysfunction are increasingly recognized as cardiac surgery complications [ 9 , 16 , 17 , 18 , 23 , 24 ]. Delirium and atypical dementia may present a different clinical spectrum from classical AD-like dementia, yet their debilitating effect on long-term recovery is profound [ 13 , 32 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

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Persistent Depletion of Neuroprotective Factors Accompanies Neuroinflammatory, Neurodegenerative, and Vascular Remodeling Spectra in Serum Three Months after Non-Emergent Cardiac Surgery

Laudański

Okeke

et al. 2022

Biomedicines

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We hypothesized that the persistent depletion of neuroprotective markers accompanies neuroinflammation and neurodegeneration in patients after cardiac surgery. A total of 158 patients underwent elective heart surgery with their blood collected before surgery (tbaseline) and 24 h (t24hr), seven days (t7d), and three months (t3m) post-surgery. The patients’ serum was measured for markers of neurodegeneration (τau, τaup181–183, amyloid β1-40/β2-42, and S100), atypical neurodegeneration (KLK6 and NRGN), neuro-injury (neurofilament light/heavy, UC-HL, and GFAP), neuroinflammation (YKL-40 and TDP-43), peripheral nerve damage (NCAM-1), neuroprotection (apoE4, BDNF, fetuin, and clusterin), and vascular smoldering inflammation (C-reactive protein, CCL-28 IL-6, and IL-8). The mortality at 28 days, incidence of cerebrovascular accidents (CVA), and functional status were followed for three months. The levels of amyloid β1-40/β1-42 and NF-L were significantly elevated at all time points. The levels of τau, S100, KLK6, NRGN, and NCAM-1 were significantly elevated at 24 h. A cluster analysis demonstrated groupings around amyloids, KLK6, and NCAM-1. YKL-40, but not TDP-43, was significantly elevated across all time points. BDNF, apoE4, fetuin, and clusterin levels were significantly diminished long-term. IL-6 and IL-8 levles returned to baseline at t3m. The levels of CRP, CCL-28, and Hsp-70 remained elevated. At 3 months, 8.2% of the patients experienced a stroke, with transfusion volume being a significant variable. Cardiac-surgery patients exhibited persistent peripheral and neuronal inflammation, blood vessel remodeling, and the depletion of neuroprotective factors 3 months post-procedure.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Persistent Depletion of Neuroprotective Factors Accompanies Neuroinflammatory, Neurodegenerative, and Vascular Remodeling Spectra in Serum Three Months after Non-Emergent Cardiac Surgery

Laudański

Okeke

et al. 2022

Biomedicines

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“…Perioperative neurocognitive disorders (PND) are characterized by cognitive impairments such as learning and memory deficits in the elderly after surgery. 1 The patient may experience difficulties performing his daily activities and an alteration of his communication abilities. 2 An increase in morbidity rate, mortality rate, hospital length of stay and frequent admissions to residential care institutions is also observed.…”

Section: Introductionmentioning

confidence: 99%

VRT-043198 Ameliorates Surgery-Induced Neurocognitive Disorders by Restoring the NGF and BNDF Expression in Aged Mice

Qi¹,

Guo²,

Li³

et al. 2022

NDT

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Background Perioperative neurocognitive disorders (PND) are common surgical complications in the elderly. Pyroptosis-associated inflammation has been suggested to participate in a series of neurocognitive diseases, including Alzheimer’s disease. Given that VRT-043198 can reportedly inhibit caspase-1-induced pyroptosis, this study sought to determine whether VRT-043198 reduced PND in a mouse model following abdominal exploratory laparotomy. Methods 20-month-old male C57/BL mice were used to establish an abdominal exploratory laparotomy (AEL) model of PND. VRT-043198 (1, 10 and 100 mg/kg) was administered intraperitoneally immediately after surgery. Thirty days post-surgery, the mice were evaluated in the Morris water maze test. Their number of neurons, neurotrophin nerve growth factor (NGF) levels and brain-derived neurotrophic factor (BDNF) were measured. In the hippocampus, A1-type astrocytes and M1-type microglia were assessed using an immunofluorescence assay and Western blot, respectively. Caspase-1 activity, IL-1β, IL-18, and PPAR-γ were also measured 24h after surgery. Results VRT-043198 administration increased the time to cross the platform and increased the ratio of distance and time in the targeted quadrant after surgery. Furthermore, it was found that VRT-043198 restored neuronal amount, increased NGF and BDNF and decreased the number of A1-type astrocytes and M1-type microglia. VRT-043198 also attenuated caspase-1 activity, downregulated IL-1β and IL-18, but increased PPAR-γ 24h post-surgery. Conclusion VRT-043198 improved PND in aged mice after abdominal exploratory laparotomy by restoring the NGF and BNDF expression. These results indicate that VRT-043198 may be a potential therapy for PND.

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“…1,19 A number of studies have reported the value of biomarkers such as neuron-specific enolase (NSE), tau, S100b proteins and glial fibrillary acidic protein (GFAP) in predicting POCD. [20][21][22] However, although these studies may help clarify the risk factors for POCD, they may not be sufficient to assist anesthesiologists in quantifying patients' risk for POCD. After all, this is often done with the help of predictive models.…”

Section: Introductionmentioning

confidence: 99%

Novel Bedside Dynamic Nomograms to Predict the Probability of Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Noncardiac Surgery: A Retrospective Study

Li¹,

Xie²,

Zhang³

et al. 2022

CIA

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Purpose Early and accurate prediction of elderly patients at high risk of postoperative cognitive dysfunction (POCD) after non-cardiac surgery will provide favorable evidence for rational perioperative management and long-term postoperative recovery. This study aimed to develop bedside dynamic nomograms to provide accurately an individualized prediction of the risk of POCD at 6-month postoperatively with patients undergoing non-cardiac surgery and to guide clinical decision-making and postoperative management. Patients and Methods We retrospectively collected patients undergoing surgical treatment at the Nanjing First Hospital between May 2020 and May 2021. We collected the data on preoperative, intraoperative, and postoperative variables. Clinical and laboratory data on admission and intraoperative variables and postoperative variables were used. We measured the performances of the nomograms using sensitivity, specificity of the receiver operating characteristic (ROC), the area under the ROC curves (AUC), the 10-fold cross-validation, and decision curve analysis (DCA). Results POCD was observed in 23 of 415 patients (5.6%) at 6-month postoperatively. The preoperative and postoperative models obtained 91.6% and 94.0% accuracy rates on the data. Compared to the preoperative model, the postoperative model had an area under the receiver characteristic curve (AUC) of 0.973 vs 0.947, corresponding to a specificity of 0.941 vs 0.918 and a sensitivity of 0.913 vs 0.870. The overall performance of the postoperative model was better than the preoperative model. Conclusion In this study, we developed novel bedside dynamic nomograms with reasonable clinical utility that can provide individualized prediction of POCD risk at 6-month postoperatively in elderly patients undergoing non-cardiac surgery at different time points based on patient admission and postoperative data. External validations are needed to ensure their value in predicting POCD in elderly patients.

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Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery

Cited by 28 publications

References 37 publications

Persistent Depletion of Neuroprotective Factors Accompanies Neuroinflammatory, Neurodegenerative, and Vascular Remodeling Spectra in Serum Three Months after Non-Emergent Cardiac Surgery

Persistent Depletion of Neuroprotective Factors Accompanies Neuroinflammatory, Neurodegenerative, and Vascular Remodeling Spectra in Serum Three Months after Non-Emergent Cardiac Surgery

VRT-043198 Ameliorates Surgery-Induced Neurocognitive Disorders by Restoring the NGF and BNDF Expression in Aged Mice

Novel Bedside Dynamic Nomograms to Predict the Probability of Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Noncardiac Surgery: A Retrospective Study

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