Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care

Study Overview
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Brief Summary
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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.

Official Title
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Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care

Conditions
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Alzheimers Disease, Postoperative Delirium, Post Operative Cognitive Dysfunction

Intervention / Treatment
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* Drug: Total intravenous anesthesia with propofol
* Drug: General anesthesia with isoflurane


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Total Intravenous Anesthesia with Propofol<br>Patients in this arm will receive general anesthesia with propofol as the primary amnestic agent. | Drug: Total intravenous anesthesia with propofol<br> <br> |
| Active Comparator: General anesthesia with Isoflurane<br>Patients in this arm will undergo general anesthesia with isoflurane as the primary amnestic agent. | Drug: General anesthesia with isoflurane<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation Between Perioperative Change in Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change | 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. | Baseline to 6 weeks | 
| Correlation Between Perioperative Change in Ratios of Cerebrospinal Fluid (CSF) Markers of Alzheimers Disease and Perioperative Cognitive Change | 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. | Baseline to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous Cognitive Index Score Change Difference Between Anesthetic Agent Groups | 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. | Baseline to 6 weeks | 
| Change in CSF Markers of Alzheimers Disease by Anesthetic Agent Group | CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane. | Baseline to 6 weeks | 
| Change in Ratio of CSF Markers of Alzheimers Disease by Anesthetic Agent Group | Change in ratio of CSF Markers of Alzheimer's Disease over time in the subjects treated with propofol versus those treated with isoflurane. | baseline to 6-weeks | 
| Perioperative CSF Tau/Abeta Ratio Change | The perioperative change in the CSF tau/Abeta ratio from the start of anesthesia/surgery to 24 hours later. | Baseline to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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isoflurane, propofol, total intravenous anesthesia, inhaled anesthetic, volatile anesthetic, anesthesia, delirium, Post Operative Cognitive Dysfunction, Alzheimer's Disease, Mild Cognitive Impairment