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。700多万 美国人目前生活在人工髋关节或膝关节，预计这将达到流行病 这是由于对提高机动性和生活质量的需求日益增长所致。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案例报告中，TJA 与手术后几年的神经认知缺陷有关。然而，长期影响 TJA种植体的植入碎片对大脑结构和认知功能的影响尚不清楚。 需要大规模的、以人群为基础的研究来评估慢性疾病的潜在贡献 暴露于TJA种植体碎片和亚型(钴/铬、聚乙烯)的风险 认知功能衰退和痴呆症。我们建议利用 罗切斯特流行病学项目(REP，R01-AG034676)，梅奥老年临床研究 (MCSA，U01-AG006786)和梅奥阿尔茨海默病研究中心(ADRC；P50 AG016574)以及梅奥诊所TJA登记，以阐明患痴呆症的长期风险 和TJA患者的认知功能障碍。 使用来自该代表的50年历史数据，我们将比较痴呆症和 调整TJA患者和匹配的非TJA受试者的人群队列亚型 对于众所周知的混杂因素(年龄、性别、肥胖)。我们将根据以下规定进一步审查风险 植入物类型。使用横断面和纵向认知和神经成像测量 作为MCSA队列的一部分收集的，我们将确定认知状态和 TJA患者认知功能的神经影像指标较非TJA患者差 研究对象。最后，我们将把金属离子水平与认知功能和结构联系起来。 神经影像和死后组织的变化。 成功完成拟议的一系列研究将是实现以下目标的关键步骤 了解长期接触TJA植入物是否与认知相关 减损。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 未知风险。潜在的下游影响是显著的，包括TJA的资格标准， 并监测高危TJA植入物和最有可能遭受系统性疾病的患者 效果。即使是负面的调查结果也会对公众健康产生重大影响，因为 向数百万现在和未来的TJA患者保证TJA的安全性。

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.