Tau Pathology in the Brain After Hip or Knee Replacement Surgery

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: * 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 with positron emission tomography (PET) and magnetic resonance imaging (MRI) scans 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.

Inclusion Criteria: Surgical cohort: * 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 Non-surgical control cohort: * Age 55 to 75 years * ASA physical status class 1 or 2 * Hip or knee osteoarthritis, recruited from the orthopedic outpatient clinic at Uppsala University Hospital * Not scheduled for surgery * Written informed consent Exclusion Criteria: Exclusion Criteria (both cohorts): * Mini-Mental State Examination (MMSE) score below 23 * History of systemic inflammatory disorder * Advanced cardiopulmonary disease