Egger’s test results for publication and selective reporting bias.

Egger’s test results for publication and selective reporting bias.</p

Forest plot of the randomized controlled trial on the association between neuronal injury biomarkers and POCD.

The plots show the correlation at 2 days (A) and 9 days (B) postoperatively.</p

PRISMA checklist.

Early biomarkers are needed to identify patients at risk of developing postoperative cognitive dysfunction (POCD). Our objective was to determine neuronal injury-related biomarkers with predictive values for this condition. Six biomarkers (S100β, neuron-specific enolase [NSE], amyloid beta [Aβ], tau, neurofilament light chain, and glial fibrillary acidic protein) were evaluated. According to the first postoperative sampling time, observational studies showed that S100β was significantly higher in patients with POCD than in those without POCD (standardized mean difference [SMD]: 6.92, 95% confidence interval [CI]: 4.44−9.41). The randomized controlled trial (RCT) showed that S100β (SMD: 37.31, 95% CI: 30.97−43.64) and NSE (SMD: 3.50, 95% CI: 2.71−4.28) in the POCD group were significantly higher than in the non-POCD group. The pooled data of observational studies by postoperative sampling time showed significantly higher levels of the following biomarkers in the POCD groups than in the control groups: S100β levels at 1 hour (SMD: 1.35, 95% CI: 0.07−2.64), 2 days (SMD: 27.97, 95% CI: 25.01−30.94), and 9 days (SMD: 6.41, 95% CI: 5.64−7.19); NSE levels at 1 hour (SMD: 0.92, 95% CI: 0.25−1.60), 6 hours (SMD: 0.79, 95% CI: 0.12−1.45), and 24 hours (SMD: 0.84, 95% CI: 0.38−1.29); and Aβ levels at 24 hours (SMD: 2.30, 95% CI: 1.54−3.06), 2 days (SMD: 2.30, 95% CI: 1.83−2.78), and 9 days (SMD: 2.76, 95% CI: 2.25−3.26). The pooled data of the RCT showed that the following biomarkers were significantly higher in POCD patients than in non-POCD patients: S100β levels at 2 days (SMD: 37.31, 95% CI: 30.97−43.64) and 9 days (SMD: 126.37, 95% CI: 104.97−147.76) and NSE levels at 2 days (SMD: 3.50, 95% CI: 2.71−4.28) and 9 days (SMD: 8.53, 95% CI: 7.00−10.06). High postoperative levels of S100β, NSE, and Aβ may predict POCD. The relationship between these biomarkers and POCD may be affected by sampling time.</div

Characteristics of the included studies.

Early biomarkers are needed to identify patients at risk of developing postoperative cognitive dysfunction (POCD). Our objective was to determine neuronal injury-related biomarkers with predictive values for this condition. Six biomarkers (S100β, neuron-specific enolase [NSE], amyloid beta [Aβ], tau, neurofilament light chain, and glial fibrillary acidic protein) were evaluated. According to the first postoperative sampling time, observational studies showed that S100β was significantly higher in patients with POCD than in those without POCD (standardized mean difference [SMD]: 6.92, 95% confidence interval [CI]: 4.44−9.41). The randomized controlled trial (RCT) showed that S100β (SMD: 37.31, 95% CI: 30.97−43.64) and NSE (SMD: 3.50, 95% CI: 2.71−4.28) in the POCD group were significantly higher than in the non-POCD group. The pooled data of observational studies by postoperative sampling time showed significantly higher levels of the following biomarkers in the POCD groups than in the control groups: S100β levels at 1 hour (SMD: 1.35, 95% CI: 0.07−2.64), 2 days (SMD: 27.97, 95% CI: 25.01−30.94), and 9 days (SMD: 6.41, 95% CI: 5.64−7.19); NSE levels at 1 hour (SMD: 0.92, 95% CI: 0.25−1.60), 6 hours (SMD: 0.79, 95% CI: 0.12−1.45), and 24 hours (SMD: 0.84, 95% CI: 0.38−1.29); and Aβ levels at 24 hours (SMD: 2.30, 95% CI: 1.54−3.06), 2 days (SMD: 2.30, 95% CI: 1.83−2.78), and 9 days (SMD: 2.76, 95% CI: 2.25−3.26). The pooled data of the RCT showed that the following biomarkers were significantly higher in POCD patients than in non-POCD patients: S100β levels at 2 days (SMD: 37.31, 95% CI: 30.97−43.64) and 9 days (SMD: 126.37, 95% CI: 104.97−147.76) and NSE levels at 2 days (SMD: 3.50, 95% CI: 2.71−4.28) and 9 days (SMD: 8.53, 95% CI: 7.00−10.06). High postoperative levels of S100β, NSE, and Aβ may predict POCD. The relationship between these biomarkers and POCD may be affected by sampling time.</div

The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the observational study.

The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the observational study.</p

The data used for analyses.

Early biomarkers are needed to identify patients at risk of developing postoperative cognitive dysfunction (POCD). Our objective was to determine neuronal injury-related biomarkers with predictive values for this condition. Six biomarkers (S100β, neuron-specific enolase [NSE], amyloid beta [Aβ], tau, neurofilament light chain, and glial fibrillary acidic protein) were evaluated. According to the first postoperative sampling time, observational studies showed that S100β was significantly higher in patients with POCD than in those without POCD (standardized mean difference [SMD]: 6.92, 95% confidence interval [CI]: 4.44−9.41). The randomized controlled trial (RCT) showed that S100β (SMD: 37.31, 95% CI: 30.97−43.64) and NSE (SMD: 3.50, 95% CI: 2.71−4.28) in the POCD group were significantly higher than in the non-POCD group. The pooled data of observational studies by postoperative sampling time showed significantly higher levels of the following biomarkers in the POCD groups than in the control groups: S100β levels at 1 hour (SMD: 1.35, 95% CI: 0.07−2.64), 2 days (SMD: 27.97, 95% CI: 25.01−30.94), and 9 days (SMD: 6.41, 95% CI: 5.64−7.19); NSE levels at 1 hour (SMD: 0.92, 95% CI: 0.25−1.60), 6 hours (SMD: 0.79, 95% CI: 0.12−1.45), and 24 hours (SMD: 0.84, 95% CI: 0.38−1.29); and Aβ levels at 24 hours (SMD: 2.30, 95% CI: 1.54−3.06), 2 days (SMD: 2.30, 95% CI: 1.83−2.78), and 9 days (SMD: 2.76, 95% CI: 2.25−3.26). The pooled data of the RCT showed that the following biomarkers were significantly higher in POCD patients than in non-POCD patients: S100β levels at 2 days (SMD: 37.31, 95% CI: 30.97−43.64) and 9 days (SMD: 126.37, 95% CI: 104.97−147.76) and NSE levels at 2 days (SMD: 3.50, 95% CI: 2.71−4.28) and 9 days (SMD: 8.53, 95% CI: 7.00−10.06). High postoperative levels of S100β, NSE, and Aβ may predict POCD. The relationship between these biomarkers and POCD may be affected by sampling time.</div

Relationship between neuronal injury and postoperative biomarkers.

(A) Brain damage occurs under the stimulation of surgery and anesthesia, injured neurons release the corresponding biomarkers into the CSF and blood through CSF-brain barrier, (B) blood-brain barrier, and (C) blood-CSF barrier. The increase of these biomarkers suggests the occurrence of POCD. NSE: neuron-specific enolase, Aβ: Amyloid beta, POCD: postoperative cognitive dysfunction, CSF: cerebrospinal fluid.</p

Flow diagram for literature selection.

Early biomarkers are needed to identify patients at risk of developing postoperative cognitive dysfunction (POCD). Our objective was to determine neuronal injury-related biomarkers with predictive values for this condition. Six biomarkers (S100β, neuron-specific enolase [NSE], amyloid beta [Aβ], tau, neurofilament light chain, and glial fibrillary acidic protein) were evaluated. According to the first postoperative sampling time, observational studies showed that S100β was significantly higher in patients with POCD than in those without POCD (standardized mean difference [SMD]: 6.92, 95% confidence interval [CI]: 4.44−9.41). The randomized controlled trial (RCT) showed that S100β (SMD: 37.31, 95% CI: 30.97−43.64) and NSE (SMD: 3.50, 95% CI: 2.71−4.28) in the POCD group were significantly higher than in the non-POCD group. The pooled data of observational studies by postoperative sampling time showed significantly higher levels of the following biomarkers in the POCD groups than in the control groups: S100β levels at 1 hour (SMD: 1.35, 95% CI: 0.07−2.64), 2 days (SMD: 27.97, 95% CI: 25.01−30.94), and 9 days (SMD: 6.41, 95% CI: 5.64−7.19); NSE levels at 1 hour (SMD: 0.92, 95% CI: 0.25−1.60), 6 hours (SMD: 0.79, 95% CI: 0.12−1.45), and 24 hours (SMD: 0.84, 95% CI: 0.38−1.29); and Aβ levels at 24 hours (SMD: 2.30, 95% CI: 1.54−3.06), 2 days (SMD: 2.30, 95% CI: 1.83−2.78), and 9 days (SMD: 2.76, 95% CI: 2.25−3.26). The pooled data of the RCT showed that the following biomarkers were significantly higher in POCD patients than in non-POCD patients: S100β levels at 2 days (SMD: 37.31, 95% CI: 30.97−43.64) and 9 days (SMD: 126.37, 95% CI: 104.97−147.76) and NSE levels at 2 days (SMD: 3.50, 95% CI: 2.71−4.28) and 9 days (SMD: 8.53, 95% CI: 7.00−10.06). High postoperative levels of S100β, NSE, and Aβ may predict POCD. The relationship between these biomarkers and POCD may be affected by sampling time.</div

Forest plot of observational studies on the association between neuronal injury biomarkers and POCD.

The plots show the correlation at 1 hour (A), 6 hours (B), 24 hours (C), 2 days (D), and 9 days (E) postoperatively.</p

Risk of bias assessment for the individual randomized controlled trial according to the Cochrane collaboration tool.

Risk of bias assessment for the individual randomized controlled trial according to the Cochrane collaboration tool.</p