{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:42:03Z","timestamp":1790185323347,"version":"4.1.0"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Postoperative cognitive dysfunction (POCD) is a frequent complication after cardiac surgery, with inconsistent evidence regarding preventive strategies. This network meta-analysis aims to evaluate and compare multiple interventions to establish an evidence-based framework for optimizing clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted for randomized controlled trials (RCTs) involving patients undergoing cardiac surgery. The study, adhering to PRISMA-NMA guidelines, included various interventions such as anesthetic agents, adjunctive drugs, and cognitive training. Methodological quality was assessed using the Cochrane Risk of Bias tool. We performed a Bayesian network meta-analysis. Rankings were interpreted according to the prespecified favorable outcome direction; therefore, lower SUCRA values denoted greater preventive effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis included 46 RCTs, encompassing 9,928 patients and 20 different intervention strategies. Most studies demonstrated a low risk of bias. Because POD and POCD were adverse-event incidence outcomes and MMSE change was coded so that smaller unfavorable postoperative decline represented benefit, lower SUCRA values were interpreted as indicating greater intervention effectiveness. Intranasal insulin, gastrodin, and cognitive training showed the lowest SUCRA values for POD-related outcomes. Gastrodin, esketamine, and dexmedetomidine showed the lowest SUCRA values for POCD-related outcomes. MMSE-change rankings were interpreted cautiously because they were based on fewer studies and were sensitive to the coding direction of change scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This network meta-analysis suggests that intranasal insulin, gastrodin, cognitive training, esketamine, and dexmedetomidine may reduce POD or POCD after cardiac surgery. However, the comparative rankings are uncertain for interventions supported by few studies, and the MMSE-change findings remain exploratory. Further high-quality RCTs are required to confirm these results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251128365<\/jats:ext-link>\n                      , identifier (CRD420251128365).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1814218","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:22:06Z","timestamp":1784910126000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The impact of different intervention methods (anesthetic adjuvant drugs, anesthetic techniques, and non-pharmacological interventions) on postoperative cognitive function in patients undergoing cardiac surgery: a systematic review and Bayesian network meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiao","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Center, The Second Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, Nei Mongol, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Center, The Second Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, Nei Mongol, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Center, The Second Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, Nei Mongol, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1097\/ALN.0000000000002334","article-title":"Recommendations for the nomenclature of cognitive change associated with Anaesthesia and Surgery-2018","volume":"129","author":"Evered","year":"2018","journal-title":"Anesthesiology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.ncl.2021.08.014","article-title":"Neurologic complications of surgery and anesthesia","volume":"40","author":"Talmasov","year":"2022","journal-title":"Neurol Clin"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1007\/s40520-021-01842-x","article-title":"Postoperative delirium after cardiac surgery of elderly patients as an independent risk factor for prolonged length of stay in intensive care unit and in hospital","volume":"33","author":"Kirfel","year":"2021","journal-title":"Aging Clin Exp Res"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"381","DOI":"10.33699\/PIS.2023.102.10.381-386","article-title":"Postoperative delirium","volume":"102","author":"Urb\u00e1nek","year":"2023","journal-title":"Rozhl Chir"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e216370","DOI":"10.1001\/jamasurg.2021.6370","article-title":"Outcomes of a delirium prevention program in older persons after elective surgery: a stepped-wedge cluster randomized clinical trial","volume":"157","author":"Deeken","year":"2022","journal-title":"JAMA Surg"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"884144","DOI":"10.3389\/fcvm.2022.884144","article-title":"Outcomes of postoperative delirium in patients undergoing cardiac surgery: a systematic review and meta-analysis","volume":"9","author":"Lin","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1001\/jamaneurol.2020.2273","article-title":"Association of delirium with long-term cognitive decline: a meta-analysis","volume":"77","author":"Goldberg","year":"2020","journal-title":"JAMA Neurol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"844","DOI":"10.3390\/diagnostics15070844","article-title":"Postoperative delirium and cognitive dysfunction after cardiac surgery: the role of inflammation and clinical risk factors","volume":"15","author":"Staicu","year":"2025","journal-title":"Diagnostics (Basel)"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e73","DOI":"10.1016\/j.lpm.2018.03.011","article-title":"Impact on the brain of the inflammatory response to surgery","volume":"47","author":"Saxena","year":"2018","journal-title":"Presse Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"376","DOI":"10.3238\/arztebl.2019.0376a","article-title":"Take into account postoperative cognitive dysfunction","volume":"116","author":"Kratz","year":"2019","journal-title":"Dtsch Arztebl Int"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e076919","DOI":"10.1136\/bmjopen-2023-076919","article-title":"Pharmacological and non-pharmacological interventions to prevent delirium after cardiac surgery: a protocol for a systematic review and meta-analysis","volume":"13","author":"Cottuli de Cothi","year":"2023","journal-title":"BMJ Open"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1053\/j.jvca.2019.09.028","article-title":"Trials focusing on prevention and treatment of delirium after cardiac surgery: a systematic review of randomized evidence","volume":"34","author":"Pieri","year":"2020","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"n160","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13054-025-05331-9","article-title":"Efficacy and safety of gastrodin in preventing postoperative delirium following cardiac surgery: a randomized placebo controlled clinical trial","volume":"29","author":"Bai","year":"2025","journal-title":"Crit Care"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"106560","DOI":"10.1016\/j.sleep.2025.106560","article-title":"Intranasal insulin enhances postoperative sleep quality and delirium in middle-aged cardiac surgery patients: a randomized controlled trial","volume":"132","author":"Yang","year":"2025","journal-title":"Sleep Med"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1053\/j.jvca.2025.04.013","article-title":"Effect of Esketamine on postoperative delirium and inflammatory response in patients undergoing off-pump coronary artery bypass grafting: a randomized controlled study","volume":"39","author":"Ju","year":"2025","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"613","DOI":"10.2147\/NSS.S439703","article-title":"Effects of intranasal insulin pretreatment on preoperative sleep quality and postoperative delirium in patients undergoing valve replacement for rheumatic heart disease","volume":"16","author":"Huang","year":"2024","journal-title":"Nat Sci Sleep"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e247361","DOI":"10.1001\/jamanetworkopen.2024.7361","article-title":"Cognitive training for reduction of delirium in patients undergoing cardiac surgery: a randomized clinical trial","volume":"7","author":"Jiang","year":"2024","journal-title":"JAMA Netw Open"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.hrtlng.2023.09.002","article-title":"A family intervention to prevent postoperative delirium in patients undergoing cardiac valve surgery: a randomized controlled study","volume":"63","author":"Lin","year":"2024","journal-title":"Heart Lung"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1213\/ANE.0000000000006925","article-title":"Effect of Esketamine on postoperative delirium in patients undergoing cardiac valve replacement with cardiopulmonary bypass: a randomized controlled trial","volume":"139","author":"Xiong","year":"2024","journal-title":"Anesth Analg"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e39470","DOI":"10.1097\/MD.0000000000039470","article-title":"Projection of visual material on postoperative delirium in patients undergoing cardiac surgery: a double blind randomized clinical trial","volume":"103","author":"M\u00e9ndez-Mart\u00ednez","year":"2024","journal-title":"Medicine (Baltimore)"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1053\/j.jvca.2024.05.027","article-title":"Comparison of Propofol-based Total intravenous anesthesia versus volatile anesthesia with Sevoflurane for postoperative delirium in adult coronary artery bypass grafting surgery: a prospective randomized single-blinded study","volume":"38","author":"Varsha","year":"2024","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e002743","DOI":"10.1136\/openhrt-2024-002743","article-title":"Effect of mannitol on postoperative delirium in patients undergoing coronary artery bypass graft: a randomised controlled trial","volume":"11","author":"Hemmati Maslakpak","year":"2024","journal-title":"Open Heart."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13054-024-04842-1","article-title":"Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial","volume":"28","author":"Huet","year":"2024","journal-title":"Crit Care"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2186326","DOI":"10.1080\/14017431.2023.2186326","article-title":"Is a hyperosmolar pump prime for cardiopulmonary bypass a risk factor for postoperative delirium? A double blinded randomised controlled trial","volume":"57","author":"Claesson Lingehall","year":"2023","journal-title":"Scand Cardiovasc J"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1186\/s13063-023-07860-6","article-title":"Effect of intranasal insulin administration on postoperative delirium prevention in elderly cardiac surgery patients: study protocol for a multicenter, double-blind, randomized, controlled trial","volume":"24","author":"Nakadate","year":"2023","journal-title":"Trials"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1111\/jcmm.17710","article-title":"Effect of transverse thoracic muscle plane block on postoperative cognitive dysfunction after open cardiac surgery: a randomized clinical trial","volume":"27","author":"Chen","year":"2023","journal-title":"J Cell Mol Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e002411","DOI":"10.1136\/openhrt-2023-002411","article-title":"Twelve-month follow-up effects of cognitive training after heart valve surgery on cognitive functions and health-related quality of life: a randomised clinical trial","volume":"10","author":"Butz","year":"2023","journal-title":"Open Heart"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"274","DOI":"10.4103\/aca.aca_106_22","article-title":"Impact of ketamine versus propofol for anesthetic induction on cognitive dysfunction, delirium, and acute kidney injury following cardiac surgery in elderly, high-risk patients","volume":"26","author":"Wittwer","year":"2023","journal-title":"Ann Card Anaesth"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1053\/j.jvca.2023.05.009","article-title":"Comparison of procedural sedation with Propofol and Dexmedetomidine during Transcatheter aortic valve replacement using the Transfemoral approach","volume":"37","author":"Vovk Racman","year":"2023","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"E408","DOI":"10.59958\/hsf.5875","article-title":"Effects of remote ischemic preconditioning on delirium and neurological function in patients undergoing cardiac surgery: a multicenter randomized controlled trial","volume":"26","author":"Liu","year":"2023","journal-title":"Heart Surg Forum"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1213\/ANE.0000000000006257","article-title":"Volatile versus Total intravenous anesthesia on postoperative delirium in adult patients undergoing cardiac valve surgery: a randomized clinical trial","volume":"136","author":"Jiang","year":"2023","journal-title":"Anesth Analg"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1053\/j.jvca.2023.04.035","article-title":"MINDDS Study Team. Association between postoperative delirium and long-term subjective cognitive decline in older patients undergoing cardiac surgery: a secondary analysis of the Minimizing Intensive Care Unit Neurological Dysfunction with Dexmedetomidine-Induced Sleep trial","volume":"37","author":"Namirembe","year":"2023","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1111\/anae.15983","article-title":"A randomised controlled trial of dexmedetomidine for delirium in adults undergoing heart valve surgery","volume":"78","author":"Wang","year":"2023","journal-title":"Anaesthesia"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"16512","DOI":"10.3390\/ijerph192416512","article-title":"Dexmedetomidine increases MMP-12 and MBP concentrations after coronary artery bypass graft surgery with extracorporeal circulation Anaesthesia without impacting cognitive function: a randomised control trial","volume":"19","author":"Kowalczyk","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1053\/j.jvca.2021.09.024","article-title":"Dexmedetomidine use in intensive care unit sedation and postoperative recovery in elderly patients post-cardiac surgery (DIRECT)","volume":"36","author":"Chitnis","year":"2022","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"294","DOI":"10.4103\/aca.ACA_85_20","article-title":"Comparison of postoperative delirium within 24 hours between ketamine and propofol infusion during cardiopulmonary bypass machine: a randomized controlled trial","volume":"24","author":"Siripoonyothai","year":"2021","journal-title":"Ann Card Anaesth"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s12871-021-01348-z","article-title":"Longitudinal assessment of preoperative dexamethasone administration on cognitive function after cardiac surgery: a 4-year follow-up of a randomized controlled trial","volume":"21","author":"Glumac","year":"2021","journal-title":"BMC Anesthesiol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"2552","DOI":"10.1111\/jocs.16661","article-title":"Intraoperative hyperoxygenation may negatively affect postoperative cognitive functions in coronary artery bypass graft operations: a randomized controlled study","volume":"37","author":"Onur","year":"2022","journal-title":"J Card Surg"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1053\/j.jvca.2020.02.035","article-title":"Perioperative Dexmedetomidine supplement decreases delirium incidence after adult cardiac surgery: a randomized, double-blind, controlled study","volume":"35","author":"Likhvantsev","year":"2021","journal-title":"Controlled Study J Cardiothorac Vasc Anesth"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0140-6736(20)30631-0","article-title":"Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomized, double-blind, controlled study","volume":"396","author":"Turan","year":"2020","journal-title":"Lancet"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"109622","DOI":"10.1016\/j.jclinane.2019.09.016","article-title":"A randomized control trial comparing prophylactic dexmedetomidine versus clonidine on rates and duration of delirium in older adult patients undergoing coronary artery bypass grafting","volume":"61","author":"Shokri","year":"2020","journal-title":"J Clin Anesth"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.3389\/fneur.2019.01293","article-title":"Effect of Ulinastatin combined with Dexmedetomidine on postoperative cognitive dysfunction in patients who underwent cardiac surgery","volume":"10","author":"Zhou","year":"2019","journal-title":"Front Neurol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1213\/ANE.0000000000004469","article-title":"Prevention of early postoperative decline: a randomized, controlled feasibility trial of perioperative cognitive training","volume":"130","author":"O'Gara","year":"2020","journal-title":"Anesth Analg"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1097\/ALN.0000000000002668","article-title":"Mathew JP; neurologic outcomes research Group of the Duke Heart Center. Intravenous lidocaine does not improve neurologic outcomes after cardiac surgery: a randomized controlled trial","volume":"130","author":"Klinger","year":"2019","journal-title":"Anesthesiology"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1001\/jama.2019.0234","article-title":"Effect of intravenous acetaminophen vs placebo combined with Propofol or Dexmedetomidine on postoperative delirium among older patients following cardiac surgery: the DEXACET randomized clinical trial","volume":"321","author":"Subramaniam","year":"2019","journal-title":"JAMA"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e008077","DOI":"10.1161\/JAHA.117.008077","article-title":"RIPHeart (remote ischemic preconditioning for heart surgery) study collaborators. RIPHeart (remote ischemic preconditioning for heart surgery) study: myocardial dysfunction, postoperative neurocognitive dysfunction, and 1 year follow-up","volume":"7","author":"Meybohm","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e0170757","DOI":"10.1371\/journal.pone.0170757","article-title":"Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: a randomized controlled trial","volume":"12","author":"Li","year":"2017","journal-title":"PLoS One"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1097\/ALN.0000000000001433","article-title":"Impact of methylprednisolone on postoperative quality of recovery and delirium in the steroids in cardiac surgery trial: a randomized, double-blind","volume":"126","author":"Royse","year":"2017","journal-title":"Placebo Control Substudy Anesthesiol"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1097\/WNF.0000000000000238","article-title":"Perioperative use of erythromycin reduces cognitive decline after coronary artery bypass grafting surgery: a pilot study","volume":"40","author":"Thomaidou","year":"2017","journal-title":"Clin Neuropharmacol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1097\/ALN.0000000000000951","article-title":"Dexmedetomidine versus Propofol sedation reduces delirium after cardiac surgery: a randomized controlled trial","volume":"124","author":"Djaiani","year":"2016","journal-title":"Anesthesiology"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1053\/j.jvca.2014.07.012","article-title":"Remote ischemic preconditioning prevents deterioration of short-term postoperative cognitive function after cardiac surgery using cardiopulmonary bypass: results of a pilot investigation","volume":"29","author":"Hudetz","year":"2015","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1007\/s00213-014-3716-x","article-title":"Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial","volume":"232","author":"Hassani","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"e64743","DOI":"10.1371\/journal.pone.0064743","article-title":"Postoperative neurocognitive dysfunction in patients undergoing cardiac surgery after remote ischemic preconditioning: a double-blind randomized controlled pilot study","volume":"8","author":"Meybohm","year":"2013","journal-title":"PLoS One"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.1161\/STROKEAHA.113.002703","article-title":"Neurologic outcome research group (NORG) of the Duke heart center. Intraoperative magnesium administration does not improve neurocognitive function after cardiac surgery","volume":"44","author":"Mathew","year":"2013","journal-title":"Stroke"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/j.1365-2044.2011.06704.x","article-title":"The influence of propofol or desflurane on postoperative cognitive dysfunction in patients undergoing coronary artery bypass surgery","volume":"66","author":"Royse","year":"2011","journal-title":"Anaesthesia"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1007\/s11596-011-0162-4","article-title":"Preventive effect of gastrodin on cognitive decline after cardiac surgery with cardiopulmonary bypass: a double-blind, randomized controlled study","volume":"31","author":"Zhang","year":"2011","journal-title":"J Huazhong Univ Sci Technolog Med Sci"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1111\/j.1399-6576.2009.01978.x","article-title":"Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery","volume":"53","author":"Hudetz","year":"2009","journal-title":"Acta Anaesthesiol Scand"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1510\/icvts.2009.217562","article-title":"Impact of clonidine administration on delirium and related respiratory weaning after surgical correction of acute type-a aortic dissection: results of a pilot study","volume":"10","author":"Rubino","year":"2010","journal-title":"Interact Cardiovasc Thorac Surg"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1053\/j.jvca.2025.05.020","article-title":"Temporal trends and severity of postoperative delirium in cardiac surgery: insights from a systematic review and Meta-analysis","volume":"39","author":"Shamsi","year":"2025","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1002\/gps.4823","article-title":"Delirium pathophysiology: an updated hypothesis of the etiology of acute brain failure","volume":"33","author":"Maldonado","year":"2018","journal-title":"Int J Geriatr Psychiatry"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/S0140-6736(09)61158-2","article-title":"Systemic infection and delirium: when cytokines and acetylcholine collide","volume":"375","author":"van Gool","year":"2010","journal-title":"Lancet"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.hrtlng.2023.02.010","article-title":"Plasma biomarkers and delirium in critically ill patients after cardiac surgery: a prospective observational cohort study","volume":"59","author":"Su","year":"2023","journal-title":"Heart Lung"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/S0140-6736(13)60688-1","article-title":"Delirium in elderly people","volume":"383","author":"Inouye","year":"2014","journal-title":"Lancet"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s41999-019-00257-2","article-title":"The financial and social costs of delirium","volume":"11","author":"Caplan","year":"2020","journal-title":"Eur Geriatr Med"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.bja.2022.12.001","article-title":"Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies","volume":"131","author":"Wang","year":"2023","journal-title":"Br J Anaesth"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"E36","DOI":"10.1532\/HSF98.20061076","article-title":"The effects of isoflurane, sevoflurane, and desflurane anesthesia on neurocognitive outcome after cardiac surgery: a pilot study","volume":"10","author":"Kanbak","year":"2007","journal-title":"Heart Surg Forum"},{"key":"ref68","first-page":"128","article-title":"The change of sevoflurane to desflurane after anesthesia induction induces rapid emergence without increased cardiovascular responses and emergence delirium in pediatric strabismus surgery patients.","volume-title":"Anesth Pain Med","author":"Hwang","year":"2015"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"e40324","DOI":"10.1097\/MD.0000000000040324","article-title":"Effects of cognitive training on cognitive function in patients after cardiac surgery: a systematic review and meta-analysis of randomized controlled trials","volume":"103","author":"Zhang","year":"2024","journal-title":"Medicine (Baltimore)"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13019-024-02520-5","article-title":"Effect of remote ischemic preconditioning on postoperative cognitive dysfunction in adult patients with general anesthesia: a meta-analysis","volume":"19","author":"Han","year":"2024","journal-title":"J Cardiothorac Surg"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13741-021-00216-1","article-title":"Influences of remote ischemic preconditioning on postoperative delirium and cognitive dysfunction in adults after cardiac surgery: a meta-analysis of randomized controlled trials","volume":"10","author":"Jing","year":"2021","journal-title":"Perioper Med (Lond)"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"814313","DOI":"10.3389\/fcvm.2021.814313","article-title":"The effect of intraoperative cerebral oximetry monitoring on postoperative cognitive dysfunction and ICU stay in adult patients undergoing cardiac surgery: an updated systematic review and Meta-analysis","volume":"8","author":"Tian","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1053\/j.jvca.2023.09.038","article-title":"Comparison of volatile anesthetics versus Propofol on postoperative cognitive function after cardiac surgery: a systematic review and Meta-analysis","volume":"38","author":"Han","year":"2024","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S0140-6736(17)31467-8","article-title":"Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial","volume":"390","author":"Avidan","year":"2017","journal-title":"Lancet"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1681531","DOI":"10.3389\/fphar.2025.1681531","article-title":"The effect of esketamine on postoperative delirium in patients undergoing general anesthesia: a systematic review and meta-analysis","volume":"16","author":"Chao-Xu","year":"2025","journal-title":"Front Pharmacol"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"20451253251339378","DOI":"10.1177\/20451253251339378","article-title":"Efficacy of intraoperative ketamine\/esketamine in the prevention of postoperative delirium: a systematic review and meta-analysis","volume":"15","author":"Chen","year":"2025","journal-title":"Ther Adv Psychopharmacol"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e089719","DOI":"10.1136\/bmjopen-2024-089719","article-title":"Efficacy of subanaesthetic esketamine on the prevention of postoperative delirium in older adult patients after cardiovascular surgery: protocol for a single-Centre, randomised, double-blind, placebo-controlled trial (SEPDOC trial) in China","volume":"15","author":"Yan","year":"2025","journal-title":"BMJ Open"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1016\/j.jagp.2021.02.043","article-title":"Repeated preoperative intranasal Administration of Insulin Decreases the incidence of postoperative delirium in elderly patients undergoing laparoscopic radical gastrointestinal surgery: a randomized, placebo-controlled, double-blinded clinical study","volume":"29","author":"Huang","year":"2021","journal-title":"Am J Geriatr Psychiatry"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"e17219","DOI":"10.7759\/cureus.17219","article-title":"A comprehensive review of intranasal insulin and its effect on the cognitive function of diabetics","volume":"13","author":"Gaddam","year":"2021","journal-title":"Cureus"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1254\/jphs.crj05006x","article-title":"New twist on neuronal insulin receptor signaling in health, disease, and therapeutics","volume":"99","author":"Wada","year":"2005","journal-title":"J Pharmacol Sci"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"e12934","DOI":"10.1111\/jne.12934","article-title":"Intranasal insulin","volume":"33","author":"Hallschmid","year":"2021","journal-title":"J Neuroendocrinol"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.bbr.2018.07.001","article-title":"Minocycline ameliorates depressive behaviors and neuro-immune dysfunction induced by chronic unpredictable mild stress in the rat","volume":"356","author":"Zhang","year":"2019","journal-title":"Behav Brain Res"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"15490","DOI":"10.1038\/s41598-021-94849-3","article-title":"Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1","volume":"11","author":"Roque","year":"2021","journal-title":"Sci Rep"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"925","DOI":"10.3233\/JAD-190280","article-title":"Intranasal insulin increases synaptic protein expression and prevents anesthesia-induced cognitive deficits through mTOR-eEF2 pathway","volume":"70","author":"Yu","year":"2019","journal-title":"J Alzheimer's Dis"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.neuroscience.2023.08.009","article-title":"Intranasal insulin alleviates traumatic brain injury by inhibiting autophagy and endoplasmic reticulum stress-mediated apoptosis through the PI3K\/Akt\/mTOR signaling pathway","volume":"529","author":"Ding","year":"2023","journal-title":"Neuroscience"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.intimp.2016.10.020","article-title":"Gastrodin relieved complete Freund's adjuvant-induced spontaneous pain by inhibiting inflammatory response","volume":"41","author":"Sun","year":"2016","journal-title":"Int Immunopharmacol"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.jpba.2008.07.013","article-title":"Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood, brain and bile by microdialysis coupled to LC-MS\/MS","volume":"48","author":"Lin","year":"2008","journal-title":"J Pharm Biomed Anal"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"4474","DOI":"10.1093\/brain\/awac236","article-title":"Activation of Wnt\/\u03b2-catenin pathway mitigates blood-brain barrier dysfunction in Alzheimer's disease","volume":"145","author":"Wang","year":"2022","journal-title":"Brain"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"514095","DOI":"10.1155\/2013\/514095","article-title":"Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson's disease model","volume":"2013","author":"Kumar","year":"2013","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1007\/s12017-018-8500-3","article-title":"Exercise training protects against aging-induced cognitive dysfunction via activation of the hippocampal PGC-1\u03b1\/FNDC5\/BDNF pathway","volume":"20","author":"Belviranl\u0131","year":"2018","journal-title":"NeuroMolecular Med"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1814218\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:22:07Z","timestamp":1784910127000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1814218\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":90,"alternative-id":["10.3389\/fneur.2026.1814218"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1814218","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]},"article-number":"1814218"}}