Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care

Phase 4

Completed

Conditions: Alzheimers Disease
Post Operative Cognitive Dysfunction
Postoperative Delirium

Interventions: Drug: General anesthesia with isoflurane
Drug: Total intravenous anesthesia with propofol

Brief Summary: This study will examine the hypothesis that changes in the cognition (i.e. thinking and memory) after anesthesia and surgery are correlated with changes in markers of Alzheimers Disease in the fluid around the brain and spinal cord (i.e. cerebrospinal fluid, or CSF), and/or changes in brain connectivity. The investigators will also examine whether different types of anesthesia have different effects on these CSF markers of Alzheimers disease, or different effects on thinking and memory after anesthesia and surgery, or differential effects on the correlation between cognitive changes and CSF marker changes.

Recruitment & Eligibility

Inclusion Criteria

Surgical patients 60 years of age or older
Surgery scheduled to last at least 2 hours (including time for anesthesia induction, etc)
English speaking ability.
Ability to give informed consent

Exclusion Criteria

Inmate of a correctional facility (i.e. prisoners).
Pregnancy
Documented or suspected family or personal history of malignant hyperthermia.
Patient unable to receive either propofol or isoflurane due to allergy or other specific contraindication.

Arm && Interventions

Group	Intervention	Description
General anesthesia with Isoflurane	General anesthesia with isoflurane	Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent.
Total Intravenous Anesthesia with Propofol	Total intravenous anesthesia with propofol	Patients in this arm will receive general anesthesia with propofol as the primary amnestic agent.

Primary Outcome Measures

Name	Time	Method
Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change	Baseline to 6 weeks	Spearman correlation was used here as the CSF markers follow a skewed distribution. Spearman correlation describes the strength of the monotonic relationship between two measures and is bounded between -1 and 1. Negative values indicate an inverse relationship while positive values mean that the variables move in tandem.
Correlation Between Perioperative Change in Ratios of Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change	Baseline to 6 weeks	Spearman correlation was used here as the ratio of CSF markers follow a skewed distribution. Spearman correlation describes the strength of the monotonic relationship between two measures and is bounded between -1 and 1. Negative values indicate an inverse relationship while positive values mean that the variables move in tandem.

Secondary Outcome Measures

Name	Time	Method
Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group	Baseline to 6 weeks	CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane.
Change in Ratio of CSF Markers of Alzheimers Disease by Anesthetic Agent Group	baseline to 6-weeks	Change in ratio of CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane.
Continuous Cognitive Index Score Change Difference Between Anesthetic Agent Groups	Baseline to 6 weeks	To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the 10 cognitive test scores from baseline. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the preoperative domain scores. The cognitive index score has a mean of zero, thus any positive score is above the mean, any negative score is below the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. A negative change score indicating decline and a positive score indicating improvement. The resulting outcome measure is unbounded with a standard deviation of 0.31 in the full surgical cohort.
Perioperative CSF Tau/Abeta Ratio Change	Baseline to 24 hours	The perioperative change in the CSF tau/Abeta ratio from the start of anesthesia/surgery to 24 hours later.

Locations (1): Duke University Medical Center
🇺🇸
Durham, North Carolina, United States