{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:55:06Z","timestamp":1791618906975,"version":"4.3.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"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. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 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-\u03b2<jats:sub>40<\/jats:sub> (A\u03b2<jats:sub>40<\/jats:sub>), amyloid-\u03b2<jats:sub>42<\/jats:sub> (A\u03b2<jats:sub>42<\/jats:sub>), 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The total incidence rate of POD was 19.60% (<jats:italic>n<\/jats:italic>\u2009=\u2009225\/1148), which was 29.3% (<jats:italic>n<\/jats:italic>\u2009=\u2009120\/409) in the SCD group and 14.2% (<jats:italic>n<\/jats:italic>\u2009=\u2009105\/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\u2009=\u20091.467, 95%CI: 1.015\u20132.120, <jats:italic>p<\/jats:italic>\u2009=\u20090.042) and P-tau (OR\u2009=\u20091.046, 95%CI: 1.028\u20131.063, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001) were risk factors for POD. The sensitivity analysis results were consistent with the above results. Mediation analysis showed that the relationship between SCD and POD was partially mediated by P-tau, which accounted for 31.25% (P-tau, IE\u2009=\u20094.279\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001). For SCD, the results of logistic regression analysis models showed that age (OR\u2009=\u20091.035, 95% CI: 1.020\u20131.049, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001), higher preoperative PSQI score (OR\u2009=\u20091.047, 95%CI: 1.014\u20131.080, <jats:italic>p<\/jats:italic>\u2009=\u20090.005), and P-tau (OR\u2009=\u20091.015, 95%CI: 1.002\u20131.028, <jats:italic>p<\/jats:italic>\u2009=\u20090.021) were risk factors for SCD, and subsequent sensitivity analysis confirmed this result after adjustment for ASA grade, height, and weight.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with SCD are more likely to develop POD undergoing total hip replacement, and SCD can mediate the occurrence of POD <jats:italic>via<\/jats:italic> P-tau.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p>This study was registered at China Clinical Trial Registry (Chictr2000033439).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2022.978297","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:54:39Z","timestamp":1669794879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Subjective cognitive decline may mediate the occurrence of postoperative delirium by P-tau undergoing total hip replacement: The PNDABLE study"],"prefix":"10.3389","volume":"14","author":[{"given":"Fanghao","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyuan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.brainres.2015.04.054","article-title":"Sevoflurane and Isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: possible link to postoperative delirium and cognitive decline","volume":"1620","author":"Acharya","year":"2015","journal-title":"Brain Res."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1111\/jgs.13406","article-title":"The American Geriatrics Society\/National Institute on Aging bedside-to-bench conference: research agenda on delirium in older adults","volume":"63","year":"2015","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1016\/j.neuropsychologia.2012.08.011","article-title":"Subjective cognitive complaints and amyloid burden in cognitively normal older individuals","volume":"50","author":"Amariglio","year":"2012","journal-title":"Neuropsychologia"},{"key":"ref12","volume-title":"Diagnostic and Statistical Manual of Mental Disorders. 5edn (DSM-5)","year":"2013"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1152\/physrev.00024.2003","article-title":"Role of tau protein in both physiological and pathological conditions","volume":"84","author":"Avila","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1037\/bul0000053","article-title":"Sleep and mental disorders: a meta-analysis of polysomnographic research","volume":"142","author":"Baglioni","year":"2016","journal-title":"Psychol. Bull."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1056\/NEJMoa1202753","article-title":"Clinical and biomarker changes in dominantly inherited Alzheimer's disease","volume":"367","author":"Bateman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-beta and tau: the trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"5424","DOI":"10.1002\/hbm.24782","article-title":"Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer's disease and mild cognitive impairment","volume":"40","author":"Chandra","year":"2019","journal-title":"Hum. Brain Mapp."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid beta: structure, biology and structure-based therapeutic development","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"491","DOI":"10.2147\/NDT.S123428","article-title":"From mild cognitive impairment to subjective cognitive decline: conceptual and methodological evolution","volume":"13","author":"Cheng","year":"2017","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/gps.3814","article-title":"Prevalence, presentation and prognosis of delirium in older people in the population, at home and in long term care: a review","volume":"28","author":"de Lange","year":"2013","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.bja.2017.11.087","article-title":"Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018","volume":"121","author":"Evered","year":"2018","journal-title":"Br. J. Anaesth."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s10072-010-0224-6","article-title":"Are subjective cognitive complaints a risk factor for dementia?","volume":"31","author":"Gallassi","year":"2010","journal-title":"Neurol. Sci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.jpainsymman.2010.08.016","article-title":"Studies comparing numerical rating scales, verbal rating scales, and visual analogue scales for assessment of pain intensity in adults: a systematic literature review","volume":"41","author":"Hjermstad","year":"2011","journal-title":"J. Pain Symptom Manag."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.2147\/CIA.S49680","article-title":"General anesthetic and the risk of dementia in elderly patients: current insights","volume":"9","author":"Hussain","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"371","DOI":"10.3233\/JAD-160461","article-title":"Preclinical amyloid-beta and Axonal degeneration pathology in delirium","volume":"55","author":"Idland","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.2147\/CIA.S201323","article-title":"Prevention of postoperative delirium in elderly patients planned for elective surgery: systematic review and meta-analysis","volume":"14","author":"Janssen","year":"2019","journal-title":"Clin. Interv. Aging"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.jalz.2014.01.001","article-title":"A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease","volume":"10","author":"Jessen","year":"2014","journal-title":"Alzheimers Dement."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"101208","DOI":"10.1016\/j.arr.2020.101208","article-title":"Synaptic basis of Alzheimer's disease: focus on synaptic amyloid beta, P-tau and mitochondria","volume":"65","author":"John","year":"2021","journal-title":"Ageing Res Rev"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1017\/S0033291796003923","article-title":"Do cognitive complaints either predict future cognitive decline or reflect past cognitive decline? A longitudinal study of an elderly community sample","volume":"27","author":"Jorm","year":"1997","journal-title":"Psychol. Med."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"748212","DOI":"10.1155\/2015\/748212","article-title":"Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease","volume":"2015","author":"Kirova","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1001\/jama.2014.13806","article-title":"The diagnosis and management of mild cognitive impairment: a clinical review","volume":"312","author":"Langa","year":"2014","journal-title":"JAMA"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s00384-019-03498-6","article-title":"Risk factors for postoperative delirium after colorectal surgery: a systematic review and meta-analysis","volume":"35","author":"Lee","year":"2020","journal-title":"Int. J. Color. Dis."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"739","DOI":"10.3233\/JAD-130035","article-title":"Diagnostic power of 24S-hydroxycholesterol in cerebrospinal fluid: candidate marker of brain health","volume":"36","author":"Leoni","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.genhosppsych.2007.12.007","article-title":"Clinical utility and validation of two instruments (the confusion assessment method algorithm and the Chinese version of nursing delirium screening scale) to detect delirium in geriatric inpatients","volume":"30","author":"Leung","year":"2008","journal-title":"Gen. Hosp. Psychiatry"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"680672","DOI":"10.3389\/fnagi.2021.680672","article-title":"Subjective cognitive decline may be associated with post-operative delirium in patients undergoing Total hip replacement: the PNDABLE study","volume":"13","author":"Lin","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s10072-018-3620-y","article-title":"Subjective cognitive decline: preclinical manifestation of Alzheimer's disease","volume":"40","author":"Lin","year":"2019","journal-title":"Neurol. Sci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.jagp.2013.09.005","article-title":"Neuropathogenesis of delirium: review of current etiologic theories and common pathways","volume":"21","author":"Maldonado","year":"2013","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref30","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":"ref31","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.jalz.2016.09.012","article-title":"Implementation of subjective cognitive decline criteria in research studies","volume":"13","author":"Molinuevo","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1093\/brain\/awx279","article-title":"Distinct influence of specific versus global connectivity on the different Alzheimer's disease biomarkers","volume":"140","author":"Mutlu","year":"2017","journal-title":"Brain"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"S58","DOI":"10.1097\/EJA.0000000000001414","article-title":"Effect of deep neuromuscular blockade on serum cytokines and postoperative delirium in elderly patients undergoing total hip replacement: a prospective single-blind randomised controlled trial","volume":"38","author":"Oh","year":"2021","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.jalz.2009.01.011","article-title":"Commentary on \"a roadmap for the prevention of dementia II: Leon Thal symposium 2008.\" subjective cognitive impairment as an antecedent of Alzheimer's dementia: policy import","volume":"5","author":"Reisberg","year":"2009","journal-title":"Alzheimers Dement."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3238\/arztebl.2014.0119","article-title":"Postoperative cognitive dysfunction","volume":"111","author":"Rundshagen","year":"2014","journal-title":"Dtsch Arztebl Int"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","article-title":"Alzheimer's disease","volume":"388","author":"Scheltens","year":"2016","journal-title":"Lancet"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1891\/rtnp.17.3.207.53186","article-title":"The measurement of delirium: review of scales","volume":"17","author":"Schuurmans","year":"2003","journal-title":"Res. Theory Nurs. Pract."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1001\/archneurol.2008.596","article-title":"Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain","volume":"66","author":"Tapiola","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13195-020-00591-9","article-title":"Functional neuroimaging in subjective cognitive decline: current status and a research path forward","volume":"12","author":"Viviano","year":"2020","journal-title":"Alzheimers Res. Ther."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13024-020-00395-3","article-title":"Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease","volume":"15","author":"Wang","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1007\/s40520-018-1008-8","article-title":"Postoperative delirium in the elderly: the potential neuropathogenesis","volume":"30","author":"Wang","year":"2018","journal-title":"Aging Clin. Exp. Res."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"109730","DOI":"10.1016\/j.jclinane.2020.109730","article-title":"Effects of different BP management strategies on postoperative delirium in elderly patients undergoing hip replacement: a single center randomized controlled trial","volume":"62","author":"Xu","year":"2020","journal-title":"J. Clin. 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