Neurocognitive Disorder after Appendectomy in the Elderly: A Natural Experiment

摘要 人们对手术和麻醉后的长期认知损害的担忧一直存在 在过去的二十年里，部分原因是没有确凿的证据；大规模的研究没有 明确地证明了暴露在麻醉和手术之间以及随后的 阿尔茨海默病和相关疾病(ADRD)的发生，也没有表现出强烈的 有证据表明存在更高的风险。这项建议旨在更好地探讨 通过对现有医疗保险数据的新分析，手术暴露和神经认知能力下降 有可能克服以前研究的局限性。本研究使用了一种新的解决方案来访问和 分析医疗保险报销申请(虚拟研究数据中心(VRDC))，使研究人员能够在经济- Cal可行的方式，通过一个安全的远程服务器分析自1999年以来的所有CMS数据。通过(1)利用 反映接受过手术的自然实验(阑尾切除的事件)，但与 生活方式或疾病相关的治疗本身可能与认知的长期变化有关， 和(2)通过使用多元匹配来解释队列中潜在的可观察到的差异，我们 有能力将暴露的8万例阑尾切除病例与匹配的对照组进行比较 在可观察到的风险因素和潜在不可观察到的风险因素之间保持密切平衡。这使我们能够更好地 进行一项大规模研究，以确定手术暴露与 随之而来的神经认知衰退的速率。目标1将完善基于索赔的诊断定义，以确定 通过对照收集的神经认知测试结果验证联邦医疗保险索赔数据导致的神经认知功能下降 《健康与退休研究》《国民健康与老龄化》中医疗保险受益人样本的研究 趋势研究和长期护理最低限度数据集中的临床评估数据。Aim 2将使用这些 进行多变量匹配队列研究以比较发展神经认知的风险的定义 随机经历阑尾炎导致阑尾切除术的患者与 未接受阑尾切除术的对照组。我们假设阑尾切除的病例将会有一个 与对照组相比，神经认知功能下降的风险增加。我们将确认所有接受过 年龄在68岁到77岁之间的阑尾切除术，并将每个病例与5名相同年龄和非常 在糖尿病、中风和高血压等神经认知能力下降的风险因素上相似，以及 广泛的合并症清单，与病例发展为阑尾炎的同一时间点，尽管 匹配已经表现出神经认知异常诊断代码的患者，并控制 比赛前的麻醉暴露。结果将通过研究危险比来检查 暴露于对照组的将包括：神经认知功能减退的诊断，疗养院入院，神经- 疗养院的认知测试，特别表明神经认知能力下降的药物，以及死亡率。 1

ABSTRACT Concern about long-term cognitive impairment following exposure to surgery and anesthesia has persisted over the past two decades, in part because there is no conclusive evidence; large-scale studies have not definitively demonstrated a lack of association between exposures to anesthesia and surgery and subsequent occurrences of Alzheimer’s disease and related disorders (ADRD), nor have they demonstrated strong evidence suggesting there is increased risk. This proposal seeks to better explore the association between operative exposure and neurocognitive decline through a new analysis of existing Medicare data that has the potential to overcome limitations of previous studies. This study uses a new solution for accessing and analyzing Medicare claims (the Virtual Research Data Center (VRDC)), allowing researchers, in an economi- cally feasible manner, to analyze all CMS data since 1999 through a secure remote server. By (1) utilizing a natural experiment that reflects an exposure to surgery (the event of appendectomy) but is not associated with lifestyle or disease related treatments that may themselves be associated with long-term changes in cognition, and (2) through the use of multivariate matching to account for potential observable differences in cohorts, we have the ability to compare an exposed cohort of 80,000 appendectomy cases with matched controls that are closely balanced for both observable and potentially unobservable risk factors. This enables us to better conduct a large-scale study determining if there is a long-term association between operative exposure and the rate of subsequent neurocognitive decline. Aim 1 will refine claims-based definitions of diagnoses that identify neurocognitive decline through validation of Medicare claims data against neurocognitive test results collected on samples of Medicare beneficiaries by the Health and Retirement Study, the National Health and Aging Trends Study, and clinical assessment data in the Long Term Care Minimum Data Set. Aim 2 will use these definitions to conduct a multivariate matched cohort study to compare the hazard for developing neurocognitive decline in patients who experienced the random event of appendicitis leading to an appendectomy versus controls who did not undergo an appendectomy. We hypothesize that cases with appendectomy will have an elevated hazard of neurocognitive decline as compared to controls. We will identify all patients who underwent appendectomy between ages 68 to 77 and match each case to 5 controls who were the same age and very similar on risk factors for neurocognitive decline such as diabetes, stroke and hypertension, as well as an extensive list of comorbidities, at the same point in time as the case developed appendicitis, while exactly matching patients who already show diagnostic codes for neurocognitive abnormalities and also controlling for anesthesia exposure prior to the match. Outcomes that will be examined by studying the hazard ratio of exposed to control groups will include: diagnoses of neurocognitive decline, nursing home admission, neuro- cognitive testing at the nursing home, drugs that specifically indicate neurocognitive decline, and mortality. 1