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 (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.
The main questions it aims to answer are:
* Does the amount of the protein tau in the brain increase in the two years after surgery? * Are changes in tau linked to inflammation in the blood and spinal fluid, and to changes in memory and thinking?
Participants will:
* Have brain scans (PET and MRI) before surgery and 12 and 24 months later * Give small samples of spinal fluid and blood * Complete memory and thinking tests at the same time points
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.
Age 55 to 75 years
ASA physical status class 1 or 2
Scheduled for hip or knee arthroplasty under regional (spinal) anesthesia at Uppsala University Hospital
Written informed consent
Mini-Mental State Examination (MMSE) score below 23
History of systemic inflammatory disorder
Advanced cardiopulmonary disease
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.
Cohort
Prospective
Hip or Knee Arthroplasty Under Spinal Anesthesia
Procedure/SurgeryElective 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.
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.
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.
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Uppsala University Hospital
Lead sponsor
Karolinska University Hospital
Collaborator
Uppsala University
Collaborator
