Neuroinflammation and Alzheimer's Pathology in Post-operative Cognitive Dysfunction: A Pilot Study
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Blood Interleukin-1 beta (IL-1β)
研究概览
简要总结
The purpose of this project is to investigate the role of both neural inflammation and pre-existing neurodegenerative pathology in the risk and pathogenesis of post-operative cognitive dysfunction (POCD). To achieve this goal, the investigators will combine blood and cerebrospinal fluid (CSF) sampling, standardized cognitive tests, and dynamic neurophysiological markers of cortical network dysfunction in the form of event-related potentials (ERPs), to assess the link between neurodegeneration and neuroinflammation in the pathogenesis of POCD.
详细描述
The purpose of this project is to investigate the role of both neural inflammation and pre-existing neurodegenerative pathology in the risk and pathogenesis of post-operative cognitive dysfunction (POCD) in 120 patients who will undergo a Total Knee Arthroscopy. The investigators will also explore neuropsychological, functional and biological measures as pre-operative risk indicators. To achieve this goal, the investigators will combine blood and cerebrospinal fluid (CSF) sampling, standardized cognitive tests, and dynamic neurophysiological markers of cortical network dysfunction in the form of event-related potentials (ERPs), to assess the link between neurodegeneration and neuroinflammation in the pathogenesis of POCD. To separate potential effects of general anesthesia from those of neuroinflammation, The investigators will recruit patients undergoing total knee replacement with the use of sedation and spinal anesthesia. To address the age risk factor, the investigators are targeting patients ages 60 and older. By using both validated and experimental biomarkers, this novel study design will isolate the effects of POCD due to systemic and neural inflammation and examine the links to pre-surgical cognitive impairment and underlying neurodegeneration as susceptibility factors.
Baseline (On the day of their final preoperative surgical visit prior to their TKA) the plan is to collect:
- Cognitive assessments
a. Montreal Cognitive Assessment b. Stroop Test c. Symbol Digit Modalities Test d. Oral Trail Making Test 2. Collect two 4-ml blood samples for biomarker evaluation
Visit 2 Pre-op (day of scheduled TKA surgery) the plan is to collect:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females 60 years or older in age
- •Subjects scheduled to undergo TKA
- •Fluent and literate in English
- •Able to give consent for themselves based upon the MacArthur Competence Assessment Tool for Clinical Research
- •Able to have a subarachnoid block with only intravenous sedation
排除标准
- •Less than 60 years of age
- •Cognitively impaired to the point where they are unable to give consent for themselves
- •Blindness or partial blindness
- •Pre-existing neurodegenerative conditions
- •Contraindication for subarachnoid block and/or requiring general anesthesia
结局指标
主要结局
Blood Interleukin-1 beta (IL-1β)
时间窗: 6 Week Post-op -Visit 5
A proinflammatory cytokine that activates astrocytes and micro ganglia
Blood Tumor necrosis factor alpha (TNF- α)
时间窗: 6-week Post-op Visit 5
A proinflammatory cytokine associated with neuroinflammation associated with neurodegenerative diseases
Cerebral Spinal Fluid Phosphorylated Tau Protein
时间窗: Pre-op Visit 2-Day of surgery
A helical protein known to be a biomarker in the cerebral spinal fluid in brains with Alzheimer's Disease
ERP response latency
时间窗: 6 Month post-op visit 6
Measurement of event related potentials in the brain
Stroop Test
时间窗: 2 Week post-op Visit 4
A neurocognitive test used to assess cognitive interference. T-Scores are computed with scores above 40 being "normal."
Montreal Cognitive Assessment
时间窗: 2 Week post-op- Visit 4
A neurocognitive test used to assess cognitive function across multiple domains. Scoring is on a scale from 0-30 with a score \>26 being normal.
Blind Montreal Cognitive Assessment
时间窗: 48 Hours post-op- Visit 3
A neurocognitive test used to assess cognitive function across multiple domains. Scoring is on a scale from 0-22 with a score \>18 being normal.
Oral Trail Making Test
时间窗: 2- Week post-op Visit 4
A neurocognitive test used to assess cognitive executive function with times for trail A \> 78 seconds and trail B \>273 seconds being deficient.
Symbol Digit Test
时间窗: 2- Week post-op Visit 4
A neurocognitive test used to assess for cerebral dysfunction scored through statistical methods with a higher score meaning higher cognitive vitality.
Blood Macrophage inflammatory protein-1 alpha (MIP-1alpha)
时间窗: 6- week Post-op Visit 5
A chemotactic cytokine which plays a role in the inflammatory process of Alzheimer's Disease
Blood Monocyte chemoattractant protein-1 (MCP-1/CCL2)
时间窗: 6 week- Post-op Visit 5
A chemotactic cytokine which plays a role in the inflammatory process through the regulation of monocytes/macrophages
ERP response amplitude
时间窗: 6 Month post-op visit 6
Measurement of event related potentials in the brain
4 AT Delirium Screening
时间窗: Post-op Visit 2- In recovery room up to 12 hours post surgery
Bedside screening to detect delirium with a score of 4 or more indicating delirium +/- cognitive impairment, and a score of 1-3 indicating possible cognitive impairment.
Grooved Pegboard Test
时间窗: 6 month post-op Visit 6
A neurocognitive test consisting of varying key shapes and matching holes used to test visual motor coordination with a higher score indicating less or no impairment based on the individual's age and sex.
National Alzheimer's Coordinating Center Cognitive Battery
时间窗: 6 month post-op Visit 6
Cognitive assessment to test for deficits across multiple domains with a score of 95/995 =physical problem; 96/996 = cognitive/behavioral problem
次要结局
未报告次要终点