RISK OF COGNITIVE IMPAIRMENT AND DEMENTIA IN TOTAL JOINT ARTHROPLASTY

摘要 全关节置换术（TJA）是美国发展最快的择期手术。超过7百万 美国人目前生活在人工髋关节或膝关节，这是预计将达到流行病 由于对改善流动性和生活质量的需求日益增长，虽然 TJA是一种安全有效的手术，人们越来越关注TJA的长期安全性。 长期接触TJA植入物。事实上，在越来越多的已发表的病例报告中， 与术后几年的神经认知缺陷有关。然而，长期影响 TJA植入物的植入碎片对大脑结构和认知功能的影响尚不清楚。 需要进行大规模的、基于人群的研究，以评估慢性炎症的潜在作用。 暴露于TJA植入物碎片和亚型（钴/铬、聚乙烯）的风险 认知能力下降和痴呆。我们建议利用 罗切斯特流行病学项目（REP，R 01-AG 034676），马约诊所衰老研究 (MCSA，U 01-AG 006786）和马约阿尔茨海默病研究中心（ADRC; P50 AG 016574）以及马约诊所TJA登记处，以阐明痴呆的长期风险 和认知功能障碍。 使用REP的50年历史数据，我们将比较痴呆症的风险， 基于人群的TJA患者队列和匹配的非TJA受试者中的亚型 已知混杂因素（年龄、性别、肥胖）。我们会根据以下资料， 植入物类型。使用横断面和纵向认知和神经影像学测量 作为MCSA队列的一部分收集，我们将确定认知状态和 与非TJA患者相比，TJA患者的认知功能神经影像学指标更差 科目最后，我们将金属离子水平与认知功能和结构相关。 神经成像和死后组织的变化 成功完成拟议的一系列研究将是朝着以下目标迈出的关键一步： 了解长期暴露于TJA植入物是否与认知功能相关 损伤我们独特的数据资源为有效解决这一问题提供了难得的机会 未知的风险潜在的下游影响很大，包括TJA的资格标准， 监测高风险TJA植入物和最有可能遭受全身性关节炎的患者， 方面的影响.即使是负面的发现也可以通过提供 对数百万当前和未来TJA患者的TJA安全性的保证。

ABSTRACT Total joint arthroplasty (TJA) is the fastest growing elective surgery in the nation. Over 7 million Americans are currently living artificial hip or knee joints and this is expected to reach epidemic proportions as a result of growing demand for improved mobility and quality of life. Although TJA is a safe and effective procedure, there is growing concern about the long-term safety of chronic exposure to TJA implants. Indeed, in a growing number of published case reports, TJA is associated with neurocognitive deficits several years after surgery. Yet, the long-term effects of implant debris from TJA implants on brain structure and cognitive function are unknown. Large scale, population-based studies are needed to assess the potential contribution of chronic exposure to TJA implant debris and subtypes (cobalt/chromium, polyethylene) to the risk of cognitive decline and dementia. We propose to leverage the unique data resources of the Rochester Epidemiology Project (REP, R01-AG034676), the Mayo Clinic Study of Aging (MCSA, U01-AG006786) and the Mayo Alzheimer's Disease Research Center (ADRC; P50 AG016574) as well as the Mayo Clinic TJA registry to elucidate the long-term risk of dementia and cognitive impairment in TJA patients. Using 5-decades of historical data from the REP, we will compare the risk of dementia and subtypes in population-based cohorts of TJA patients and matched non-TJA subjects adjusting for well-known confounders (age, sex, obesity). We will further examine the risk according to implant types. Using cross-sectional and longitudinal cognition and neuroimaging measures collected as part of the MCSA cohort, we will determine whether cognitive status and neuroimaging markers of cognitive function are worse in TJA patients compared with non-TJA subjects. Finally, we will correlate metal ion levels with cognitive function and structural changes on neuroimaging and postmortem tissues. Successful completion of the proposed series of studies will be a key step towards understanding whether chronic exposure to TJA implants is associated with cognitive impairment. Our unique data resources offer a rare opportunity to efficiently address this unknown risk. Potential downstream effects are significant including eligibility criteria for TJA, and monitoring high risk TJA implants and patients who are most likely to suffer from systemic effects. Even negative findings can exert a significant public health impact by providing reassurance about the safety of TJA to millions of current and future TJA patients.