Treatment of Perioperative Neurocognitive Disorders With Olfactory Enrichment

The presence of postoperative delirium will be defined according to 3D-CAM, which includes four entries: acute onset and fluctuating course, inattention, disorganized thinking and altered level of consciousness. To diagnose delirium, both the first and second criteria have to be present plus the third and/or fourth criteria. Every participant will be assessed twice daily after anesthesia/surgery from postoperative day 1 to postoperative day 3, with the first assessment between 8:00 and 10:00. The second assessment will be between 15:00 and 17:00.

Participants' cognitive function will be assessed at baseline, on postoperative day 21, and at postoperative month 6 using a battery of neuropsychological tests, including the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test Retention (HVLTRet), Hopkins Verbal Learning Test Total Recall (HVLTTR), Brief Visuospatial Memory Test Total Recall (BVMTTR), Brief Visuospatial Memory Test Delayed Recall (BVMTDR), Benton Judgment of Line Orientation (JLO), Digit Span Test (DST), Verbal Fluency Test (VFT) and Trail Making Test (TMT). Cognitive Change Index will be calculated by subtracting baseline scores from postoperative scores in each of the neuropsychological tests. Delayed neurocognitive recovery or postoperative neurocognitive disorder will be defined as by a decrease by one or more standard deviations in at least two of the neuropsychological tests from the baseline to 21 days or 6 months after anesthesia/surgery.

Severity of delirium will be assessed by the CAM-S. CAM-S includes 10 items: acute onset or symptom fluctuation, inattention, disorganized thinking, altered level of consciousness, disorientation, memory impairment, perceptual disturbances, psychomotor agitation, psychomotor retardation and sleep-wake cycle disturbance. Each item is scored as absent (0), mild (1) or marked (2), except acute onset or fluctuation, which is scored as absent (0) or present (1). The sum of CAM-S ranges from 0 (none) to 19 (most severe). The Delirium Symptom Interview (DSI) Daily will be used to determine CAM-S grades. The incidence of postoperative delirium will also be referred to the records by nurses on duty.

Severity of delayed neurocognitive recovery and postoperative neurocognitive disorder will be assessed by battery of neuropsychological tests at baseline, on postoperative day 21, and at postoperative month 6. The scores of neuropsychological tests indicate cognitive functions which can reflect the severity of delayed neurocognitive recovery and postoperative neurocognitive disorder.

Activities of daily living will be assessed using the Chinese version of the ADL scale at baseline, and on postoperative day 21 days and 6 months after anesthesia/surgery, including a Physical Self-Maintenance Scale and an Instrumental Activities of daily living at baseline (before the surgery) and follow-ups. There are a total of 14 items in the Activities of daily living. For each item, scoring is determined by a 4-point coding system: 1 = 'can do it myself,' 2 = 'have some difficulty but can still do it by myself,' 3 = 'need help to do it,' and 4 = 'cannot do it at all.' A higher score therefore indicates greater impairment in activities of daily living. Specifically, a total activities of daily living score of 14 signifies no impairment, scores of 15-21 indicate mild impairment, and scores of ≥22 reflect severe impairment. Participants with Activities of daily living scores of more than 22 points will be considered to have substantive impairment in Activities of daily living.

Five milliliters of blood will be collected from participants immediately before and after anesthesia/surgery, 3 days, 21 days and 6 months postoperatively. Blood samples will be centrifuged at 500 g for 10 minutes, and the plasma supernatant will be collected. The plasma will be collected in EDTA tubes, immediately placed on ice, and then stored in a -80°C freezer until analysis. The samples will be thawed at the time of measurement. Tau-PT217 concentrations in plasma will be measured using Nanoneedle technology.

Olfactory function will be assessed at baseline and on postoperative day 3, 21 and 6 months after anesthesia/surgery. The assessment will include odor threshold (scored from 1 to 20) and odor identification (scored from 0 to 16) tests, using pen-like odor dispensing devices to evaluate nasal chemosensory performance.