Treatment of Perioperative Neurocognitive Disorders With Olfactory Enrichment
NCT Number: NCT06488807
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Perioperative Neurocognitive Disorder
Interventions: OTHER: Olfactory Enrichment|OTHER: Sham
Sponsor: Shanghai 10th People's Hospital
Collaborators: National Natural Science Foundation of China
Sex: ALL
Age: OLDER_ADULT
Enrollment: 324
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (CARE_PROVIDER, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-01
Completion Date: 2028-07-31
Locations: Shanghai Tenth People's Hospital, Shanghai, China

Summary:
Perioperative neurocognitive disorder (PND) is one of the most common postoperative complications among elderly patients. However, the mechanism and targeted intervention of PND remains unclear. Our previous clinical studies demonstrated the association between olfactory impairment and PND. Moreover, our translational studies showed that anesthesia/surgery induced olfactory impairment and caused cognitive impairment in mice and olfactory enrichment could prevent the anesthesia/surgery-induced cognitive impairment. However, there was no clinical investigation to determine whether olfactory enrichment can mitigate PND in elderly patients. Therefore, we propose determining whether olfactory enrichment can prevent and/or treat PND in elderly patients.

Primary Outcome Measures: Postoperative Delirium Incidence., Postoperative delirium will be defined according to 3D-CAM, which is a 3-minute diagnostic assessment for CAM-defined delirium including four features: acute onset and fluctuating course, inattention, disorganised thinking and altered level of consciousness. To diagnose delirium, both the first and second criteria have to be present and the third and/or fourth criteria. Therefore, every participant will be assessed twice daily after surgery from postoperative day 1 to postoperative day 3, with the first assessment at 8:00-10:00. The second assessment will be at 15:00-17:00., from postoperative day 1 to 3 or at discharge
Secondary Outcome Measures: Postoperative Delirium Severity., The 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., from postoperative day 1 to 3 or at discharge|Plasma Tau Levels., Five ml of blood was collected from the participants within 3 days preoperatively, within 1 hour before anesthesia and surgery, immediately after anesthesia and surgery and from postoperative day 1 to 3. Blood samples were centrifuged at 500 g for 10 minutes, and plasma supernatant was collected. The plasma was collected in an EDTA tube and was immediately placed on ice. The plasma was then stored in a -80 °C degree freezer until the time of measurement when the samples were thawed. All of the measures in the current study were performed using the same methods with double-blind design. Tau-PT217 and Tau-PT181 in plasma will be measured by Nanoneedle., within 3 days preoperatively, within 1 hour before anesthesia and surgery, immediately after anesthesia and surgery, from postoperative day 1 to 3 or at discharge|Olfactory Function., Olfactory function will be assessed within 3 days preoperatively, on postoperative day 3 or at discharge by using odor threshold (score: 1 to 16) and odor identification (score: 0 to 16) tests., within 3 days preoperatively, on postoperative day 3 or at discharge|Cognitive Function related to Delirium., We will use neuropsychological tests including Montreal Cognitive Assessment Scale (MoCA), Hopkins Verbal Learning Test Retention (HVLTRet), Hopkins Verbal Learning Total Recall (HVLTTR), Brief Visuospatial Memory Test Total Recall (BVMTTR), Brief Visuospatial Memory Test Delayed Recall (BVMTDR), Benton Judgment of Line Orientation (JLO), Trails Making Test (A/B), Digital Span Test (DST, forward and back-forward), and Verbal Fluency Test (VFT)., within 3 days preoperatively, postoperative day 21 and 6 months after anesthesia and surgery|Visual Analogue Scale., Pain will be assessed using the Visual Analogue Scale (VAS). Participants will be scored according to the severity of their pain, from no pain (0) to most painful (10)., within 3 days preoperatively, from postoperative day 1 to 3 or at discharge|Activities of Daily Living., Activities of daily living (ADL) will be assessed using the Chinese version of the ADL scale, including a Physical Self-Maintenance Scale and an Instrumental ADL at baseline (within 3 days preoperatively) and follow-ups (postoperative day 21 and 6 months after anesthesia and surgery). There are a total of 14 items in the ADL. 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.' The total ADL score ranges from 14 to 56 points, and higher ADL scores indicate lower ADL. Participants with ADL scores of more than 22 points (cut-off score) will be defined as having impairment in ADL., within 3 days preoperatively, postoperative day 21 and 6 months after anesthesia and surgery