Markers of Alzheimers Disease After Propofol or Isoflurane Anesthesia

Study Overview
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Brief Summary
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Previous work in animal models suggests that inhalational anesthetic agents may accelerate Alzheimer's disease pathogenesis, but it is unclear to what extent this may happen in humans. Here, the investigators propose to measure Alzheimer's disease-related neural markers in the cerebrospinal fluid (CSF) of patients exposed to anesthesia while undergoing neurosurgical procedures that require lumbar drain placement. Patients will be randomized to either receive inhalation anesthesia with isoflurane or intravenous anesthesia with propofol. CSF and blood samples will each be collected at the induction of anesthesia, and then again ten and twenty-four hours later. CSF samples will be assayed for amyloid beta, tau, and other Alzheimer's disease-associated markers; blood samples will be assayed for serum inflammatory markers and used for genotyping studies. These studies should clarify the effect of common anesthetic agents on Alzheimer's disease related neural markers.

Official Title
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The Effect of Isoflurane Versus Propofol Anesthesia on Alzheimers Disease CSF Markers

Conditions
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General Anesthesia

Intervention / Treatment
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* Drug: Propofol
* Drug: Isoflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18 and above seen in neurosurgical clinic, and scheduled for operative aneurysm repair or other neurosurgical procedure necessitating lumbar drain placement. ability to speak English. ability to understand consent forms, and to give informed consent. Exclusion Criteria: age less than 18 lumbar drain is not placed not eligible for one of the anesthetics (inhaled isoflurane or IV propofol) inmate of a correctional facility (i.e. prisoners). pregnancy. Pregnancy is ruled out as standard of care before cranial surgery, based on clinical history and/or HCG testing

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propofol based intravenous anesthesia<br>patients will receive propofol based intravenous anesthesia | Drug: Propofol<br>* patients randomized to the propofol arm of the study will receive general anesthesia with propofol<br>|
| Experimental: Isoflurane Based Inhaled Anesthesia<br>patients will receive isoflurane based inhaled anesthesia | Drug: Isoflurane<br>* patients randomized to the isoflurane arm of the study will receive general anesthesia with isoflurane<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of cerebrospinal fluid tau to amyloid beta |  | twenty four hours after the induction of anesthesia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the relationship between anesthetic exposure and CSF biomarker changes |  | up to 24 hrs after induction of anesthesia | 
| the relationship between anesthetic exposure and CSF biomarker changes, and demographics (age, gender, and race) |  | up to 24 hrs after induction of anesthesia | 
| the relationship between CSF biomarker changes and serum markers of metabolic and/or inflammatory status |  | up to 24 hrs after induction of anesthesia | 
| the relationship between anesthetic exposure and biomarker changes and serum markers of metabolic and/or inflammatory status |  | up to 24 hrs after induction of anesthesia | 
| the relationship between anesthetic exposure and biomarker changes and neuroimaging results obtained as dictated by routine standard of care |  | up to 24 hours after induction of anesthesia | 
| the relationship between anesthetic exposure and biomarker changes and depth of anesthesia, based on average BIS (bispectral index) monitoring signal |  | up to 24 hours after induction of anesthesia | 
| the relationship between anesthetic exposure and biomarker changes and the time of day that surgery is performed |  | up to 24 hours after induction of anesthesia | 
| the relationship between anesthetic exposure and biomarker changes with genetic polymorphisms in ApoE (apolipoprotein E) and other genes related to inflammation, metabolism, brain function and/or Alzheimer's disease |  | up to 24 hours after induction of anesthesia | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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General Anesthesia, Alzheimers Disease, Cognitive decline