ADRD after Injury in the Elderly Study: Alzheimer's Disease or Related Dementia after Injury in the Elderly Study

老年人受伤后 ADRD 研究：老年痴呆症或相关痴呆症研究

• 批准号: 10020156
• 负责人: Mina F Nordness
• 金额: $ 7.59万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-08 至 2021-08-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10020156
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Analgesics; Anesthesia procedures; Anesthesiology; Anesthetics; Antipsychotic Agents; Biological Markers; Characteristics; Cognition; Cohort Studies; Coma; Critical Illness; Delirium; Dementia; Development; Dose; Education; Educational Background; Elderly; Emergency Situation; Exposure to; Frequencies; Future; General Anesthesia; HMGB1 Protein; Hospitals; Impaired cognition; Infrastructure; Inhalation; Injury; Intensive Care Units; Intervention; Intravenous; Investigation; Lead; Life; Medical; Mentors; Nervous System Trauma; Neuropsychology; Operative Surgical Procedures; Parents; Patients; Pediatric cohort; Pharmaceutical Preparations; Plasma; Population; Postoperative Period; Preventive; Prospective cohort; Public Health; Publishing; Rehabilitation therapy; Reproducibility; Research Personnel; Role; Sedation procedure; Severities; Severity of illness; Socioeconomic Status; Surgical Intensive Care; Survivors; Training; Trauma; Traumatic Brain Injury; Traumatic injury; Work; cohort; comorbidity; injured; neuroinflammation; post-operative cognitive dysfunction; programs; prospective; public health relevance; sedative; severe injury

Project Summary Exposure to surgery with general anesthesia has been associated with cognitive dysfunction in older adults. This post-operative cognitive dysfunction has been studied across elective surgical populations, and when persistent, represents an Alzheimer’s Disease and Related Dementia (ADRD). Our group recently published on the impact of surgery and anesthesia exposure on ADRD in a prospective multicenter cohort study of >1,000 medical and surgical intensive care unit (ICU) patients without pre-existing dementia. Controlling for pre- and in-hospital patient characteristics, we demonstrated that neither surgery with anesthesia exposure, nor age, was independently associated with ADRD at 12 months. This controversial lack of association between surgery and ADRD requires reproducibility in other populations, and has never been studied in a large critically injured cohort. Injured patients vary significantly on their age, illness severity, and need for surgery. Timing, frequency, and type of surgery are also variable as many of these patients have multisystem injuries. There have been no studies investigating surgery-specific or dose-dependent relationships of surgery with anesthesia on the development of ADRD. Injured patients also may sustain traumatic brain injury, delirium, coma, and sedation which all may influence future ADRD. Neuroinflammation is one proposed mechanism of cognitive dysfunction after surgery, primarily in pediatric cohorts. The impact of neuroinflammation is unclear in a critically ill injured elderly cohort. Some work in uninjured critically ill patients has demonstrated association of ADRD and neuroinflammatory biomarkers such as high mobility group box-1 (HMGB1) or S100B, but has not been studied in the injured adult. Impact: The ADRD after Injury in the Elderly Study will be the first to investigate the effects of surgery and anesthesia exposure on ADRD and associated neuroinflammation in critically injured patients controlling for age, co-morbidities, pre-injury education level, injury severity, type of neurologic injury (i.e. traumatic brain injury, delirium), with a specific focus on the elderly. This study will feature a 450-subject nested prospective cohort investigation within my Primary Mentors’ R01 cohort of 900 critically injured patients. This will provide me with a unique opportunity to lead my own nested cohort investigation while leveraging the essential infrastructure of the Parent cohort and pursuing advanced training via a Master in Public Health.

项目摘要 全身麻醉手术暴露与认知功能障碍有关， 老年人这种术后认知功能障碍已经在选择性外科手术中进行了研究。 当持续存在时，代表阿尔茨海默病和相关痴呆症（ADRD）。 我们小组最近发表了关于手术和麻醉暴露对ADRD的影响的文章， 一项对1,000例以上内科和外科重症监护室（ICU）患者进行的前瞻性多中心队列研究 没有老年痴呆症控制住院前和住院患者的特征，我们 结果表明，手术与麻醉暴露和年龄都不是独立相关的， 12个月时患有ADRD。 手术和ADRD之间缺乏联系这一有争议的问题需要在 其他人群，从未在一个大的严重受伤的队列中进行过研究。受伤的病人各不相同 年龄、疾病严重程度和手术需求都有显著影响。时间、频率和类型 外科手术也是可变，因为这些患者中的许多具有多系统损伤。没有发生 研究了手术与麻醉的手术特异性或剂量依赖性关系， ADRD的发展。受伤的病人也可能遭受创伤性脑损伤，谵妄，昏迷， 和镇静剂，这些都可能影响未来的ADRD。神经炎症是一种被提出的机制 手术后认知功能障碍，主要是在儿科队列中。神经炎症的影响 在一个危重受伤的老年队列中尚不清楚。在未受伤的重症患者中开展的一些工作 已证实ADRD与神经炎性生物标志物（如高迁移率组）相关 box-1（HMGB 1）或S100 B，但尚未在受伤的成人中进行研究。 影响：老年人受伤后的ADRD研究将是第一个调查其影响的研究。 外科手术和麻醉暴露对严重创伤患者ADRD和相关神经炎症的影响 控制年龄、合并症、损伤前教育水平、损伤严重程度、 神经损伤（即创伤性脑损伤、谵妄），特别关注老年人。本研究 我将在我的主要导师R 01中进行一项450例受试者的嵌套前瞻性队列研究 900名重症患者的队列研究。这将为我提供一个独特的机会来领导我自己的 嵌套队列研究，同时利用父母队列的基本基础设施， 通过公共卫生硕士进行高级培训。