An observational study in Postoperative Cognitive Dysfunction, Alzheimer Disease and Tauopathies, sponsored by Uppsala University Hospital. Recruiting at 1 site in Sweden. Open to participants aged 55 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-10-15.
Sponsored by Uppsala University Hospital · 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.
The study is a prospective observational study that will be carried out in Uppsala University Hospital. Adults aged 55-75 years who are healthy otherwise American Society of Anesthesiologists (ASA) 1-2 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.
The main questions it aims to answer are:
Participants will:
Researchers 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.
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.
Aims: 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.
Design: 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.
Methods: All assessments are performed at baseline (before surgery), and at 12 and 24 months after surgery, with corresponding time points in the control cohort.
Analysis: 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.
269 studies on the registry are indexed under Postoperative Cognitive Complications; 56 are open to participants now.
This study's planned enrollment of 30 is below the median of 100 across 115 observational studies indexed under Postoperative Cognitive Complications.
Browse Postoperative Cognitive Complications studies →Uppsala University Hospital is the lead sponsor of 73 studies on the registry; 19 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Inclusion Criteria:
Surgical cohort:
Non-surgical control cohort:
Exclusion Criteria:
Exclusion Criteria (both cohorts):
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.
Procedure: Hip or Knee Arthroplasty Under Spinal Anesthesia
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
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.
Also known as: Total hip replacement, Total knee replacement
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.
Time frame: baseline, 12 and 24 months
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.
Time frame: 24 months
Plan to share: No — Individual participant data will not be shared. The data include sensitive health information (brain imaging, cerebrospinal fluid and cognitive data), and sharing is restricted by the EU General Data Protection Regulation (GDPR), Swedish law and the conditions of the ethical approval (Swedish Ethical Review Authority, Dnr 2024-05719-02).
Start is estimated for Apr 2029; primary completion for Apr 2029, 0 months later.
Of 73 non-industry observational studies under Postoperative Cognitive Complications, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 11 and three quarters within 61. This study's planned 0 months is below that.
Counting every sponsor, half of 74 studies reached it within 31 months; a quarter within 11 and three quarters within 61.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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