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Many elderly patients undergoing surgical procedures already have impaired cognitive (memory/concentration) status. Patients with pre-existing cognitive impairment, or dementia, may benefit from modified anesthesia techniques. It is estimated that one in eight people age 65 and older has Alzheimers disease. More so, nearly half of people that are 85 years or older have Alzheimers disease. Currently, both spinal (regional) and inhalational (general) anesthesia, are used in patients undergoing common urological, orthopedic, and general surgical procedures. Inhalational anesthesia has been associated with higher risk of memory impairment in experimental (animal) and human studies. However, currently, there are simply no large or good enough studies to be sure that inhalational anesthesia is responsible for causing dementia and Alzheimers disease.The proposed study investigates if elderly patients (65 years and older) undergoing spinal anesthesia (patient is awake or slightly sedated) are less likely to develop dementia and Alzheimers disease for up to 2 years after surgery, when compared to inhalational anesthesia (patient is kept asleep with gas anesthetic). The investigators will also test all patients for the presence of apolipoprotein (ApoE-Îμ4 type of gene that is present in 15-20% of patients), and beta-amyloid tau protein (present in cerebrospinal fluid) that are known risk factors for Alzheimers disease. The particular strength of this study is that it takes into account whether the frequency and/or severity of dementia and Alzheimers disease is different in patients with and without these markers. The investigators believe that this study will make a major contribution to better understanding of development of Alzheimers disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Spinal anesthesia group | Active Comparator | Spinal anesthesia group will receive bupivacaine 10-15mg anesthesia according to the standard practice. Supplemental sedation with intravenous anesthetics (midazolam/propofol) will be optional. |
|
| General anesthesia group | Active Comparator | Induction of anesthesia will be achieved with propofol 1.5-2mg/kg and fentanyl 1-3g/kg. Anesthesia will be maintained with inhalational anesthesia (isoflurane or sevoflurane) at the discretion of anesthesiologist in charge of the case. A mixture of Air/O2 will be used to maintain adequate oxygenation. Nitrous oxide will not be used. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Spinal anesthesia group: bupivacaine 10-15mg | Drug |
| ||
| General anesthesia group: induction propofol 1.5-2mg/kg and fentanyl 1-3g/kg, maintained with isoflurane or sevoflurane |
| Measure | Description | Time Frame |
|---|---|---|
| Assessing the incidence of early dementia | Change from baseline, hospital discharge (3 day average), 3 months, 1 year, and 2 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| George Djaiani, MD | Toronto General Hospital, University Health Network | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Toronto General Hospital, University Health Network | Toronto | Ontario | M5G 2C4 | Canada | ||
| William Osler Health Centre |
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The proposed study will be a prospective, multicenter, cluster randomization clinical trial comparing two different anesthetic techniques in elderly patients (> 65 years of age) undergoing urology/orthopedic/general surgery. The study will follow a cluster design; patients undergoing orthopedic or vascular surgery will have spinal anesthesia, where standard practice. Patients undergoing urology or general surgery will receive general anesthesia, also where it is standard practice. Patients with severe dementia will be excluded.
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| Drug |
|
| Blood test | Genetic | DNA will be tested for the presence of ε4 allele of the apolipoprotein E gene |
|
| Lumbar spinal tap | Other | 1ml of cerebrospinal fluid (CSF) removed and stored for further analysis of amyloid tau protein after completion of the study |
|
| Montreal Cognitive Assessment (MOCA) and MMSE | Behavioral |
|
| Toronto |
| Ontario |
| M9V 1R8 |
| Canada |
| Pauls Stradins Clinical University Hospital | Riga | LV 1002 | Latvia |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D005283 | Fentanyl |
| D007530 | Isoflurane |
| D000077149 | Sevoflurane |
| D006403 | Hematologic Tests |
| D013129 | Spinal Puncture |
| D000073216 | Mental Status and Dementia Tests |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D008738 | Methyl Ethers |
| D004987 | Ethers |
| D009930 | Organic Chemicals |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D001706 | Biopsy |
| D013048 | Specimen Handling |
| D003943 | Diagnostic Techniques, Neurological |
| D011677 | Punctures |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
| D009483 | Neuropsychological Tests |
| D011581 | Psychological Tests |
| D004191 | Behavioral Disciplines and Activities |
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