RISK OF COGNITIVE IMPAIRMENT AND DEMENTIA IN TOTAL JOINT ARTHROPLASTY

全关节置换术中认知障碍和痴呆的风险

• 批准号: 10743158
• 负责人: Hilal Maradit Kremers
• 金额: $ 33.3万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10743158
• 关键词: Address; Age; Aging; Alzheimer' s Disease; American; Amyloid beta-Protein; Autopsy; Brain; Case Study; Ceramics; Characteristics; Chromium; Chronic; Classification; Clinic; Clinical; Cobalt; Cognition; Cognitive; Corrosion; Data; Dementia; Education; Eligibility Determination; Epidemic; Epidemiology; Exposure to; Formalin; Freezing; Funding; Future; Genotype; Goals; Hip Joint; Hip Prosthesis; Immune response; Impaired cognition; Implant; Individual; Infrastructure; Ions; Kidney Diseases; Knee Prosthesis; Knee joint; Knowledge; Laboratories; Long-Term Effects; Measures; Medical Record Linkage; Metals; Methods; Monitor; Morbidity - disease rate; Negative Finding; Nerve Degeneration; Neurocognitive; Neurocognitive Deficit; Obesity; Operative Surgical Procedures; Paraffin Embedding; Patient risk; Patients; Policies; Polyethylenes; Population Study; Procedures; Public Health; Publishing; Quality of life; Records; Registries; Replacement Arthroplasty; Research; Risk; Risk Factors; Role; Safety; Series; Serum; Structure; Surface; Synovial Fluid; System; Time; Tissue Embedding; Tissues; Titanium; United States; brain tissue; cerebrovascular pathology; clinical risk; cognitive function; cognitive testing; cohort; cost; data registry; data resource; dementia risk; experience; high risk; improved mobility; mortality; neuroimaging; neuroimaging marker; neuropathology; neurotoxicity; population based; procedure safety; prospective; public health relevance; recruit; sex; vascular risk factor

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.

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是一个 安全和有效的程序，有越来越多的关注长期安全的慢性接触 TJA植入物。事实上，在越来越多的已发表病例报告中，TJA与以下疾病相关： 术后几年出现神经认知障碍。然而，植入物碎片对大脑的长期影响 结构和认知功能是未知的。 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）的认知风险 衰退和痴呆。我们建议利用罗切斯特的独特数据资源 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 临床TJA登记研究，以阐明TJA患者痴呆和认知障碍的长期风险。 使用REP的50年历史数据，我们将比较痴呆症和亚型的风险， TJA患者和匹配的非TJA受试者的基于人群的队列调整了众所周知的 混杂因素（年龄、性别、肥胖）。我们将根据植入物类型进一步检查风险。使用 作为MCSA的一部分收集的横截面和纵向认知和神经影像学指标 队列，我们将确定是否认知状态和认知功能的神经影像学标志物， 与非TJA受试者相比，TJA患者更差。最后，我们将把金属离子水平与 的原因 管理补充如下：我们认识到需要使用更敏感的方法， 测量组织中的金属含量因此，代替福尔马林固定的石蜡包埋组织，我们 将使用冷冻的脑组织在第四年，我们承担了大量额外成本，并开发和 验证了新的实验室方法，以“超痕量”水平测量脑组织中的金属水平。 认知功能和神经影像学和死后组织的结构变化。 成功完成拟议的一系列研究将是迈向了解的关键一步 长期暴露于TJA植入物是否与认知障碍有关。潜在 下游影响是显著的，包括TJA的资格标准和监测高风险TJA 植入物和患者谁是最有可能遭受系统的影响。即使是负面的发现， 通过向数百万人提供关于TJA安全性的保证，发挥重大的公共卫生影响。 目前和未来的TJA患者。

项目成果

Correlation of Blood Metal Concentrations with Cognitive Scores and Neuroimaging Findings in Patients with Total Joint Arthroplasty.

• DOI: 10.3233/jad-221182
• 发表时间: 2023
• 期刊: JOURNAL OF ALZHEIMERS DISEASE
• 影响因子: 4
• 作者: Beba, Alican;Peterson, Stephanie M.;Brennan, Peter C.;O'Byrne, Jamie;Machulda, Mary M.;Jannetto, Paul I.;Vemuri, Prashanthi;Lewallen, David G.;Kremers, Hilal Maradit;Vassilaki, Maria
• 通讯作者: Vassilaki, Maria