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首页> 外文学位 >A Retrospective Study of Cholinesterase Inhibitors for Alzheimer's Disease: The Effect of Cerebrovascular Disease on Patient Outcomes and the Impact of Biases on the Results.
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A Retrospective Study of Cholinesterase Inhibitors for Alzheimer's Disease: The Effect of Cerebrovascular Disease on Patient Outcomes and the Impact of Biases on the Results.

机译：胆碱酯酶抑制剂对阿尔茨海默氏病的回顾性研究：脑血管疾病对患者结果的影响以及偏见对结果的影响。

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摘要

Introduction: Dementia may be caused by Alzheimer's disease (AD), cerebrovascular disease (CVD), or a combination of both. When CVD is associated with dementia, survival is thought to be reduced. It is unclear whether treatment with cholinesterase inhibitors (ChEIs), which has been found to improve cognitive symptoms and global function in AD patients, has similar benefits in vascular forms of dementia.;Methods: A retrospective cohort study was undertaken using the Regie de l'Assurance Maladie du Quebec (RAMQ) databases to examine the time to NHP or death for AD patients aged 66+, with or without CVD, treated with ChEIs between July 1, 2000, and June 30, 2003. Because ChEIs are approved only for AD in Canada, a ChEI prescription was used as a surrogate for an AD diagnosis. Concomitant CVD was identified on the basis of a lifetime diagnosis of stroke or endarterectomy, or a diagnosis of transient ischemic attack within the six months prior to the index date. Separate analyses were performed for patients with persistent ChEI use and those who discontinued ChEI therapy. Seven Cox proportional hazard regression models which varied in the definition of the index date (start of follow-up) and the duration of follow-up were used to evaluate the impact of immortal time bias.;Results: 4,428 patients met inclusion criteria for AD with CVD; 13,512 were classified as having AD alone. For the composite endpoint of NHP or death, 1,000-day survival rates were lower among AD patients with versus without CVD (p0.01), but absolute differences were very small (84% vs. 86% with continuous ChEI use; 77% vs. 78% with discontinuous ChEI therapy). Of the secondary endpoints, time to death was shorter for patients with versus without CVD, but time to NHP did not differ between groups. In the primary, unbiased analysis, no association was found between ChEI treatment type and death or NHP. However, after introduction of immortal time bias, a strong differential effect was observed.;Limitations: Results may have been affected by selection (misclassification) bias, between-group differences in smoking and body mass index (information on which was not available in the RAMQ databases), and duration of ChEI therapy.;Objectives: The present study was designed to determine whether co-existing CVD is associated with survival or time to nursing home placement (NHP) among AD patients treated with ChEIs. Findings of poorer outcomes in patients with versus without CVD might argue against the use of ChEIs for AD patients in whom CVD co-exists. The objective of a second analysis was to assess for the first time in patients with AD the potential impact of immortal time (and follow-up) bias on risk for these outcomes.;Conclusions: Associations between co-existing CVD and time to NHP or death appeared to be of little clinical relevance among AD patients treated with ChEIs. The lack of difference between AD patients with and without CVD suggests that CVD should not be used as a reason to deny AD patients access to ChEI treatment. Properly accounting for unexposed person-time in the analysis eliminates biased estimates of drug efficacy.;Keywords: cholinesterase inhibitors; dementia; Alzheimer's disease; cerebrovascular disease; administrative database
机译：简介：痴呆症可能是由阿尔茨海默氏病（AD），脑血管疾病（CVD）或两者的结合引起的。当CVD与痴呆症相关时，据认为存活率降低。尚不清楚胆碱酯酶抑制剂（ChEIs）的治疗是否能改善AD患者的认知症状和整体功能，在血管性痴呆中是否具有类似的益处。方法：采用Regie de l进行的回顾性队列研究“魁北克省医疗机构（RAMQ）的数据库检查了2000年7月1日至2003年6月30日期间接受ChEI治疗的66岁以上AD患者（无论是否患有CVD）达到NHP或死亡的时间。因为ChEI仅获批准用于在加拿大的AD中，使用ChEI处方作为AD诊断的替代物。根据对卒中或动脉内膜切除术的终生诊断，或对索引日期前六个月内的短暂性缺血发作的诊断，确定伴有CVD。对持续使用ChEI的患者和中止ChEI治疗的患者进行了单独的分析。使用七个Cox比例风险回归模型，评估指标日期（随访开始）和随访持续时间的变化，以评估不朽时间偏差的影响。结果：4,428例患者符合AD纳入标准CVD有13,512位被归类为仅患有AD。对于NHP或死亡的复合终点，有和没有CVD的AD患者的1000天生存率均较低（p <0.01），但绝对差异非常小（连续使用ChEI的患者为84％vs. 86％； 77％vs. 77％vs.不连续的CHEI治疗占78％）。在次要终点中，有和没有CVD的患者的死亡时间更短，但两组之间达到NHP的时间没有差异。在无偏见的主要分析中，未发现ChEI治疗类型与死亡或NHP之间存在关联。但是，在引入不朽的时间偏差后，观察到了强烈的差异效果。局限性：结果可能受到选择（误分类）偏差，群体间吸烟差异和体重指数的影响。目的：本研究旨在确定在并用ChEIs治疗的AD患者中，共存的CVD是否与生存或护理院安置时间（NHP）有关。在有或没有CVD的患者中发现不良结局可能会反对在CVD共存的AD患者中使用ChEI。第二项分析的目的是首次评估AD患者中不朽时间（和随访）偏倚对这些结局风险的潜在影响。结论：CVD与NHP或时间的相关性在接受ChEIs治疗的AD患者中，死亡似乎与临床无关。有和没有CVD的AD患者之间缺乏差异，这表明不应将CVD用作拒绝AD患者接受ChEI治疗的理由。在分析中适当考虑未接触人员的时间可以消除药物疗效的偏倚估计。痴呆;阿尔茨海默氏病;脑血管疾病;管理数据库

著录项

  • 作者

    Charbonneau, Claudie.;

  • 作者单位

    Universite de Montreal (Canada).;

  • 授予单位 Universite de Montreal (Canada).;
  • 学科 Biology Neuroscience.;Health Sciences Epidemiology.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 284 p.
  • 总页数 284
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 肿瘤学;
  • 关键词

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