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。尽管TJA是一家 安全有效的程序，人们越来越关注慢性接触的长期安全性 到TJA植入物。事实上，在越来越多的已发表的案例报告中，TJA与 手术后几年出现神经认知缺陷。然而，长期的影响是将碎片植入大脑 结构和认知功能尚不清楚。 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)对认知风险的影响 衰老和痴呆症。我们建议利用罗切斯特独特的数据资源 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 临床TJA登记，以阐明TJA患者患痴呆症和认知障碍的长期风险。 使用来自该代表的50年历史数据，我们将比较 TJA患者和匹配的非TJA受试者的基于人群的队列调整 混杂因素(年龄、性别、肥胖)。我们将根据植入物的类型进一步检查风险。vbl.使用 作为MCSA的一部分收集的横断面和纵向认知和神经成像测量 队列，我们将确定认知状态和认知功能的神经成像标记物是否 与非TJA患者相比，TJA患者的情况更差。最后，我们将金属离子能级与 其原因是 管理补充如下：我们认识到需要使用更敏感的方法来 测量组织上的金属含量。因此，我们没有福尔马林固定的石蜡包埋组织，而是 将使用冰冻的脑组织。在第四年，我们产生了大量的额外成本，并开发了 经过验证的新实验室方法，可以在“超痕量”水平上测量脑组织中的金属含量。 神经影像和死后组织的认知功能和结构变化。 成功完成拟议的一系列研究将是迈向理解 长期接触TJA植入物是否与认知障碍有关。潜力 下游影响显著，包括TJA的资格标准，以及监测高风险TJA 植入物和最有可能遭受全身影响的患者。即使是负面的调查结果也可以 通过向数百万人提供关于TJA安全性的保证，对公共卫生产生重大影响 目前和未来的TJA患者。

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 implant debris 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 adjustingfor 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 The reason for the admin supplement is the following: We recognized the need to use more sensitive methods for measuring metal levels on tissues. Therefore, instead of formalin-fixed paraffin-embedded tissues, we will use frozen brain tissues. In year 4, we incurred substantial additional costs and developed and validated new laboratory methods to measure metal levels in brain tissue at ‘ultra-trace’ levels. 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. 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 systemiceffects. 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.