{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:38:46Z","timestamp":1790095126980,"version":"4.0.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007535","name":"B. Braun Medical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007535","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The relationship between preoperative serum uric acid (SUA) and cerebrospinal fluid (CSF) Alzheimer-related biomarkers were investigated to determine whether high SUA is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The participants were selected from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study and the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study. The logistic regression equation was used to analyze the risk factors and protective factors of POD. The interaction term (SUA \u00d7 Sex) was introduced into the linear model to explore the potential modification effects of sex on the identified correlations. We analyzed the mediating effects of Alzheimer-related biomarkers. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of SUA and Alzheimer-related biomarkers in predicting POD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with POD had elevated SUA level (PNDRFAP: <jats:italic>p<\/jats:italic> = 0.002, PNDABLE: <jats:italic>p<\/jats:italic> &amp;lt; 0.001). Preoperative SUA level was positively correlated with CSF phosphorylated tau (P-tau) (<jats:italic>p<\/jats:italic> = 0.027) and \u03b2-amyloid42 (A\u03b2<jats:sub>42<\/jats:sub>)\/P-tau (<jats:italic>p<\/jats:italic> = 0.023). Interaction analysis did not find any modification effect of sex. The relationship between SUA and POD was partially mediated by CSF P-tau (15.3%). ROC curve showed that the model combining SUA and Alzheimer-related biomarkers had better performance in predicting POD [area under the curve (AUC) = 0.880; <jats:italic>p<\/jats:italic> &amp;lt; 0.001], and the predictive model is accurate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High SUA may enhance CSF P-tau level, thus increasing the risk of POD, and the model combining SUA and Alzheimer-related biomarkers can accurately predict the occurrence of POD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2022.909738","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T06:56:23Z","timestamp":1657781783000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Potential Value of Serum Uric Acid in the Identification of Postoperative Delirium in Geriatric Patients Undergoing Knee Replacement"],"prefix":"10.3389","volume":"14","author":[{"given":"Fei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhui","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyv","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Lin","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":[[2022,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"116866","DOI":"10.1016\/j.jns.2020.116866","article-title":"Associations of serum uric acid with incident dementia and cognitive decline in the ARIC-NCS cohort","volume":"414","author":"Alam","year":"2020","journal-title":"J. Neurol. Sci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1042\/bj3400143","article-title":"When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid","volume":"340","author":"Bagnati","year":"1999","journal-title":"Biochem. J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.3233\/JAD-160028","article-title":"Serum uric acid and its association with longitudinal cognitive change among urban adults","volume":"52","author":"Beydoun","year":"2016","journal-title":"J. Alzheimers Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1097\/HJH.0000000000000701","article-title":"Serum uric acid and the risk of cardiovascular and renal disease","volume":"33","author":"Borghi","year":"2015","journal-title":"J. Hypertens"},{"key":"B5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0165-0173(00)00019-9","article-title":"Tau protein isoforms, phosphorylation and role in neurodegenerative disorders","volume":"33","author":"Bu\u00e9e","year":"2000","journal-title":"Brain Res. Brain Res. Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jns.2013.11.041","article-title":"Oxidative balance, homocysteine, and uric acid levels in older patients with Late Onset Alzheimer's Disease or Vascular Dementia","volume":"337","author":"Cervellati","year":"2014","journal-title":"J. Neurol. Sci"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1016\/j.jagp.2021.02.001","article-title":"Association of depressive symptoms with postoperative delirium and CSF biomarkers for Alzheimer's disease among hip fracture patients","volume":"29","author":"Chan","year":"2021","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3760\/cma.j.cn112150-20200724-01053","article-title":"[Association of blood uric acid and cognitive impairment in oldest-old aged 80 years and older in 9 longevity areas of China]","volume":"55","author":"Chen","year":"2021","journal-title":"Zhonghua Yu Fang Yi Xue Za Zhi"},{"key":"B9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s11739-014-1098-z","article-title":"Serum uric acid and impaired cognitive function in a cohort of healthy young elderly: data from the Brisighella Study","volume":"10","author":"Cicero","year":"2015","journal-title":"Intern. Emerg. Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1097\/HJH.0b013e3282f240bf","article-title":"Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system","volume":"26","author":"Corry","year":"2008","journal-title":"J. Hypertens"},{"key":"B11","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1097\/NEN.0b013e318217a118","article-title":"Brain oligomeric \u03b2-amyloid but not total amyloid plaque burden correlates with neuronal loss and astrocyte inflammatory response in amyloid precursor protein\/tau transgenic mice","volume":"70","author":"DaRocha-Souto","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1093\/geront\/gnv100","article-title":"Delirium screening: a systematic review of delirium screening tools in hospitalized patients","volume":"55","author":"De","year":"2015","journal-title":"Gerontologist"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e2534","DOI":"10.1002\/brb3.2534","article-title":"The relationship between body mass index and postoperative delirium","volume":"12","author":"Deng","year":"2022","journal-title":"Brain Behav."},{"key":"B14","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1093\/brain\/awn316","article-title":"Serum uric acid and cognitive function and dementia","volume":"132","author":"Euser","year":"2009","journal-title":"Brain"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1097\/ALN.0000000000001378","article-title":"Intensive care unit delirium: a review of diagnosis, prevention, and treatment","volume":"125","author":"Hayhurst","year":"2016","journal-title":"Anesthesiology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12974-018-1163-z","article-title":"Evidence of the impact of systemic inflammation on neuroinflammation from a non-bacterial endotoxin animal model","volume":"15","author":"Huang","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"B17","doi-asserted-by":"publisher","first-page":"941","DOI":"10.7326\/0003-4819-113-12-941","article-title":"Clarifying confusion: the confusion assessment method. A new method for detection of delirium","volume":"113","author":"Inouye","year":"1990","journal-title":"Ann. Intern. Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"375","DOI":"10.3233\/JAD-150069","article-title":"Progranulin and Amyloid-\u03b2 Levels: relationship to neuropsychology in Frontotemporal and Alzheimer's disease","volume":"46","author":"K\u00f6rtv\u00e9lyessy","year":"2015","journal-title":"J. Alzheimers. Dis"},{"key":"B19","first-page":"1045","article-title":"Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kinmen","volume":"27","author":"Lin","year":"2000","journal-title":"J. Rheumatol"},{"key":"B20","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":"B21","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1080\/10376178.2015.1041999","article-title":"Mediation analysis in nursing research: a methodological review","volume":"52","author":"Liu","year":"2016","journal-title":"Contemp. Nurse"},{"key":"B22","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.jalz.2011.05.2243","article-title":"The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers","volume":"7","author":"Mattsson","year":"2011","journal-title":"Alzheimers Dement"},{"key":"B23","doi-asserted-by":"publisher","first-page":"a006338","DOI":"10.1101\/cshperspect.a006338","article-title":"Neurotoxicity of amyloid \u03b2-protein: synaptic and network dysfunction","volume":"2","author":"Mucke","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1024\/0040-5930\/a000770","article-title":"[Hyperuricemia, gout and cardiovascular diseases]","volume":"73","author":"Murray","year":"2016","journal-title":"Ther. Umsch"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1002\/pro.3275","article-title":"Amyloidogenesis of Tau protein","volume":"26","author":"Nizynski","year":"2017","journal-title":"Protein Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4","DOI":"10.4097\/kja.d.18.00073.1","article-title":"Postoperative delirium","volume":"72","author":"Oh","year":"2019","journal-title":"Korean J. Anesthesiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1097\/YCO.0b013e328357f51c","article-title":"Prevention and treatment options for postoperative delirium in the elderly","volume":"25","author":"Popp","year":"2012","journal-title":"Curr. Opin. Psychiatry"},{"key":"B28","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1042\/BST20140319","article-title":"The blood-brain barrier endothelium: a target for pro-inflammatory cytokines","volume":"43","author":"Rochfort","year":"2015","journal-title":"Biochem. Soc. Trans"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1212\/01.wnl.0000277468.10236.f1","article-title":"Serum uric acid and brain ischemia in normal elderly adults","volume":"69","author":"Schretlen","year":"2007","journal-title":"Neurology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1172\/JCI42344","article-title":"Uric acid transport and disease","volume":"120","author":"So","year":"2010","journal-title":"J. Clin. Invest"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.2147\/NDT.S113077","article-title":"Production of inflammatory cytokines, cortisol, and A\u03b21-40 in elderly oral cancer patients with postoperative delirium","volume":"12","author":"Sun","year":"2016","journal-title":"Neuropsychiatr. Dis. Treat"},{"key":"B32","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":"B33","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1159\/000346606","article-title":"The relation of uric acid to brain atrophy and cognition: the Rotterdam Scan Study","volume":"41","author":"Verhaaren","year":"2013","journal-title":"Neuroepidemiology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"772795","DOI":"10.3389\/fnagi.2021.772795","article-title":"Potential value of cerebrospinal fluid progranulin in the identification of postoperative delirium in geriatrics patients undergoing knee replacement: the perioperative neurocognitive disorder and biomarker LifestylE study","volume":"13","author":"Wang","year":"2021","journal-title":"Front. Aging Neurosci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"7379","DOI":"10.1007\/s00216-014-8132-x","article-title":"Rapid screening and detection of XOD inhibitors from S. tamariscina by ultrafiltration LC-PDA-ESI-MS combined with HPCCC","volume":"406","author":"Wang","year":"2014","journal-title":"Anal. Bioanal. Chem"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nrn.2015.1","article-title":"Tau in physiology and pathology","volume":"17","author":"Wang","year":"2016","journal-title":"Nat. Rev. Neurosci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.ijcard.2015.08.110","article-title":"Relation of serum uric acid to cardiovascular disease","volume":"213","author":"Wu","year":"2016","journal-title":"Int. J. Cardiol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/acn3.58","article-title":"Preoperative cerebrospinal fluid \u03b2-Amyloid\/Tau ratio and postoperative delirium","volume":"1","author":"Xie","year":"2014","journal-title":"Ann. Clin. Transl. Neurol"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.909738\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T06:56:57Z","timestamp":1657781817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.909738\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":38,"alternative-id":["10.3389\/fnagi.2022.909738"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.909738","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]},"article-number":"909738"}}