The Neuroprotective Effect of Dexmedetomidine Preserving Brain Functional Connectivity in Elderly Patients

• Status: Not yet recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Older patients are more prone to adverse cognitive outcomes such as postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Both conditions are associated with an increased risk of death, functional decline, and health care costs. The presence of pro-inflammatory cytokines in the central nervous system has detrimental effects on the regulation of neurotransmitter signaling in different areas of the brain, especially the hippocampus, ultimately resulting in neuronal dysfunction and cognitive decline. Neuroimaging studies have provided important information on the structural and functional networks involved in the pathogenesis of POD and POCD. Strong evidence has shown a decrease in the integrity of the default mode network (DMN), along a continuum from normal aging to mild cognitive impairment and Alzheimer's disease. Dexmedetomidine is a highly selective alpha-2 adrenergic agonist with sedative and analgesic properties but minimal respiratory effects. Several studies have shown that dexmedetomidine reduces serum pro-inflammatory cytokines and POCD. The expected results are to analyze the change in the integrity of the DMN from the preoperative period to the first weeks after discharge given by the two anesthetic strategies (SEVO vs SEVODEX). In addition, it seeks to evaluate (1) Changes in the integrity of the DMN at 3 months. (2) Modulation of structural changes in white matter integrity as measured by DTI. (3) Patient performance in specific cognitive function tests and serum inflammation biomarkers between the pre- and postoperative period. For the analysis, the Generalized Linear Model (GLM) will be used, in which the integrity of the DMN is the dependent variable. As predictors will use the anesthetic groups (SEVO and SEVODEX) and the measurement time (preoperative, 1 to 3 weeks after discharge and 3 months later as levels). With this work we aim to provide a mechanistic explanation of the observed neuroprotective effects of dexmedetomidine in anesthesia protocols for elderly patients. Furthermore, this work will possibly promote functional connectivity as a possible clinical biomarker of cognitive impairment in this vulnerable population.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pontificia Universidad Catolica de Chile
• Treatments: Dexmedetomidine

Criteria

Inclusion Criteria:

• ASA I, II or III.

• Body mass index (BMI) <35 kg/m2.

• Scheduled at least 6 days prior to surgery to allow adequate time for the baseline assessment.

• Planned admission to the hospital for at least 2 days.

Exclusion Criteria:

• Active delirium diagnosed with the Confusion Assessment Method (CAM).

• Mild cognitive impairment or dementia diagnosed with the Spanish-language version of the Montreal Cognitive Assessment MoCA-S1-2 score (score <20 points).

• In case the patient cannot answer the MoCA test, the instrument AD8-Ch will be applied.

• Hospitalization within 3 months prior to enrollment to minimize risk of recent delirium history.

• Severely frail condition defined with the Clinical Frailty Scale (CFS ≥7).

• Inability to perform cognitive tests due to legal blindness or severe deafness

• History of schizophrenia or psychosis.

• Harmful alcohol use or alcohol dependence (AUDIT score ≥16 considering the standard drink equivalent determined by MINSAL).

• History of benzodiazepines or marihuana consumption (more than 3 days per week).

• Unable to pass assessment for capacity to provide informed consent.

• Claustrophobia.