[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100659856":3},{"organization":4,"outcomesModule":7,"designInfo":18,"detailedDescription":21,"studyPopulation":22,"armGroups":23,"interventions":32,"overallOfficials":17,"centralContacts":41,"locations":50,"responsibleParty":72,"collaborators":76,"id":81,"slug":82,"hasResults":83,"nctId":84,"briefTitle":85,"officialTitle":86,"acronym":87,"eligibilityCriteria":88,"healthyVolunteers":83,"sex":89,"minAge":90,"maxAge":91,"enrollmentInfo":92,"targetDuration":95,"studyType":96,"phases":17,"briefSummary":97,"conditions":98,"keywords":105,"overallStatus":52,"whyStopped":17,"lastUpdateSubmitDate":113,"lastUpdatePostDateStruct":114,"startDateStruct":117,"completionDateStruct":119,"leadSponsor":120,"locationsCount":121},{"fullName":5,"class":6},"Uppsala University Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":17,"otherOutcomes":17},[9,13],{"measure":10,"description":11,"timeFrame":12},"Change in Tau Levels in the Hippocampus on PET Scan","Tau protein levels in the brain will be measured with a PET scan using the tracer \\[18F\\]RO948. Brain regions will be outlined automatically on each participant's MRI using allocated software. The cerebellum will be the reference region. The main region of interest is the hippocampus. Tau levels will be reported as binding potential, which has no units; higher values mean more tau. The change from the first scan to the follow-up scan will be compared between the surgery group and the non-surgery group.","baseline, 12 and 24 months",{"measure":14,"description":15,"timeFrame":16},"Change in Brain Tau Burden Measured by [18F]RO948 PET","Tau protein levels in the brain will be measured with a PET scan using the tracer \\[18F\\]RO948. Brain regions will be outlined automatically on each participant's MRI using appropriate software. The cerebellum will be the reference region. The main region of interest is the hippocampus. Tau levels will be reported as binding potential, which has no units; higher values mean more tau. The change from the first scan to the follow-up scan will be compared between the surgery group and the non-surgery group.","24 months",null,{"allocation":17,"interventionModel":17,"interventionModelDescription":17,"primaryPurpose":17,"observationalModel":19,"timePerspective":20,"maskingInfo":17},"COHORT","PROSPECTIVE","Background: Postoperative neurocognitive decline is common in older surgical patients and has been associated with an increased risk of later dementia. Experimental studies show that surgery and anesthesia can trigger neuroinflammation, tau phosphorylation and tau aggregation, and clinical studies have shown acute increases in cerebrospinal fluid (CSF) and blood markers of neuronal injury (tau, neurofilament light) after surgery. Whether surgery leads to increased tau pathology in the human brain is unknown.\n\nAims: To translate preclinical findings of surgery-induced tau pathology to surgical patients by (A) mapping individual brain tau trajectories, cognitive function and biomarkers of neurodegeneration and brain injury during 24 months after surgery compared with matched non-surgical controls, and (B) linking individual patterns of inflammatory and neurodegenerative biomarkers and immune cell phenotypes to tau pathology and neurocognitive outcomes using pattern-recognition analysis.\n\nDesign: Prospective, longitudinal observational cohort study at Uppsala University Hospital, Sweden. A surgical cohort (n=20) undergoing elective hip or knee arthroplasty under spinal anesthesia is compared with a non-surgical control cohort (n=10) with hip or knee arthrosis, matched by age and sex. Participants are aged 55-75 years, ASA physical status 1-2, with MMSE score of 23 or higher.\n\nMethods: All assessments are performed at baseline (before surgery), and at 12 and 24 months after surgery, with corresponding time points in the control cohort.\n\n* Tau PET imaging with the second-generation tracer \\[18F\\]RO948 on a simultaneous PET-MR camera. Tau burden is quantified as binding potential in automatically delineated cortical regions (FreeSurfer), with cerebellar cortex as reference region.\n* Cognitive assessment with the Neuropsychological Test Battery (NTB; composite z-score and the domains memory, psychomotor speed and executive function) and the Clinical Dementia Rating scale (CDR).\n* CSF (4 mL) collected by spinal puncture; at baseline this is done in connection with the spinal anesthesia, before injection of the anesthetic.\n* Venous blood samples (25 mL) for plasma, serum and immune cell phenotyping by flow cytometry.\n* Biomarkers: NfL, tau and GFAP by Simoa, and broad inflammatory and glial protein panels by proximity extension assay (Olink).\n\nAnalysis: Mixed models and multivariate methods (e.g. principal component analysis) will be used to relate individual biomarker and immune cell trajectories to changes in brain tau burden and cognitive outcomes, and to compare the surgical and control cohorts.","Adults aged 55 to 75 years with hip or knee osteoarthritis (ASA physical status 1-2), recruited at Uppsala University Hospital, Sweden. The surgical cohort includes patients scheduled for hip or knee arthroplasty under spinal anesthesia. The non-surgical control cohort includes patients from the orthopedic outpatient clinic who are not scheduled for surgery, matched to the surgical cohort by age and sex.",[24,29],{"label":25,"type":17,"description":26,"interventionNames":27},"Surgical Cohort","Adults aged 55-75 years, ASA physical status 1-2, undergoing elective hip or knee arthroplasty under spinal anesthesia as part of routine care. Tau PET-MR, cognitive testing, CSF and blood sampling before surgery and at 12 and 24 months after surgery, n=20.",[28],"Procedure: Hip or Knee Arthroplasty Under Spinal Anesthesia",{"label":30,"type":17,"description":31,"interventionNames":17},"Non-Surgical Control Cohort","Adults aged 55-75 years, ASA physical status 1-2, with hip or knee arthrosis not scheduled for surgery. Tau PET-MR, cognitive testing, CSF and blood sampling at baseline and at 12 and 24 months, n=10",[33],{"type":34,"name":35,"description":36,"armGroupLabels":37,"otherNames":38},"PROCEDURE","Hip or Knee Arthroplasty Under Spinal Anesthesia","Elective primary hip or knee arthroplasty performed as part of routine clinical care; the procedure and anesthesia are not assigned by the study, and surgery is the exposure of interest. All patients receive spinal anesthesia, with optional light propofol sedation during surgery. No general anesthesia is used. Before the intrathecal injection, 4 mL of cerebrospinal fluid is collected for research as the baseline sample. Tau PET-MR, cognitive testing and blood sampling are performed before surgery, with repeat PET-MR, cognitive testing, CSF and blood sampling at 12 and 24 months after surgery.",[25],[39,40],"Total hip replacement","Total knee replacement",[42,47],{"name":43,"role":44,"phone":45,"phoneExt":17,"email":46},"Miklos Lipcsey, Professor","CONTACT","+46186110000","miklos.lipcsey@uu.se",{"name":48,"role":44,"phone":45,"phoneExt":17,"email":49},"Sana Asif, M.D, PhD","sana.asif@uu.se",[51],{"facility":5,"status":52,"city":53,"state":17,"zip":54,"country":55,"countryCode":56,"cosmosGeoPoint":57,"geoPoint":62,"contacts":63},"RECRUITING","Uppsala","751 85","Sweden","SE",{"type":58,"coordinates":59},"Point",[60,61],17.63889,59.85882,{"lat":61,"lon":60},[64,66,67,70],{"name":43,"role":44,"phone":65,"phoneExt":17,"email":46},"+46-18-6110000",{"name":48,"role":44,"phone":45,"phoneExt":17,"email":49},{"name":68,"role":69,"phone":17,"phoneExt":17,"email":17},"Lars I Eriksson, Professor","SUB_INVESTIGATOR",{"name":71,"role":69,"phone":17,"phoneExt":17,"email":17},"Gunnar Antoni, Professor",{"type":73,"investigatorFullName":74,"investigatorTitle":75,"investigatorAffiliation":5,"oldNameTitle":17,"oldOrganization":17},"PRINCIPAL_INVESTIGATOR","Miklos Lipcsey","Professor, Senior Consultant",[77,79],{"name":78,"class":6},"Karolinska University Hospital",{"name":80,"class":6},"Uppsala University","100659856","tau-pathology-in-the-brain-after-hip-or-knee-replacement-surgery-100659856",false,"NCT07871487","Tau Pathology in the Brain After Hip or Knee Replacement Surgery","Surgery and Postoperative Tau Pathology in Humans: A Translational Imaging and Biochemical Study to Explore Surgery-Induced Hallmarks of Alzheimer's Dementia","TAU-PET","Inclusion Criteria:\n\nSurgical cohort:\n\n* Age 55 to 75 years\n* ASA physical status class 1 or 2\n* Scheduled for hip or knee arthroplasty under regional (spinal) anesthesia at Uppsala University Hospital\n* Written informed consent\n\nNon-surgical control cohort:\n\n* Age 55 to 75 years\n* ASA physical status class 1 or 2\n* Hip or knee osteoarthritis, recruited from the orthopedic outpatient clinic at Uppsala University Hospital\n* Not scheduled for surgery\n* Written informed consent\n\nExclusion Criteria:\n\nExclusion Criteria (both cohorts):\n\n* Mini-Mental State Examination (MMSE) score below 23\n* History of systemic inflammatory disorder\n* Advanced cardiopulmonary disease","ALL","55 Years","75 Years",{"count":93,"type":94},30,"ESTIMATED","24 Months","OBSERVATIONAL","The goal of this observational study is to study whether major surgery is linked to changes in the brain that are typical of Alzheimer's disease.\n\nThe study is a prospective observational study that will be carried out in Uppsala University Hospital. Adults aged 55-75 years who are healthy otherwise (ASA1) having a hip or knee replacement under spinal anesthesia, and a comparison group of people of the same age and sex with hip or knee arthrosis who are not having surgery will be included.\n\nThe main questions it aims to answer are:\n\n* Does the amount of the protein tau in the brain increase in the two years after surgery?\n* Are changes in tau linked to inflammation in the blood and spinal fluid, and to changes in memory and thinking?\n\nParticipants will:\n\n* Have brain scans (PET and MRI) before surgery and 12 and 24 months later\n* Give small samples of spinal fluid and blood\n* Complete memory and thinking tests at the same time points\n\nResearchers will compare the surgery group with the non-surgery group to see whether surgery is associated with more tau in the brain and with changes in memory and thinking.",[99,100,101,102,103,104],"Postoperative Cognitive Dysfunction","Alzheimer Disease","Tauopathies","Neuroinflammation","Arthroplasty, Replacement, Hip","Arthroplasty, Replacement, Knee",[106,107,108,109,110,111,112],"Tau PET","[18F]RO948","Postoperative Neurocognitive Disorder","Cerebrospinal Fluid Biomarkers","Spinal Anesthesia","Surgery-Induced Inflammation","Cognitive Decline","2026-10-06",{"date":115,"type":116},"2026-10-13","ACTUAL",{"date":118,"type":94},"2029-04-01",{"date":118,"type":94},{"name":5,"class":6},1]