Wang Y, Li M, Kazis L E, Xia W
Geriatric Research Education and Clinical Center, Bedford VA Healthcare System, Bedford, MA, USA.
Department of Mathematical Sciences, Bentley University, Waltham, MA, USA.
JAR Life. 2023 Jun 20;12:35-45. doi: 10.14283/jarlife.2023.8. eCollection 2023.
The criteria for use of Alzheimer's disease (AD) drug Leqembi recommended by the Department of Veterans Affairs (VA) include patients aged 65 years or older with mild cognitive impairment (MCI) or mild AD. Comorbidities that include hypertension, hyperlipidemia, and diabetes are common among these patients.
Our objective is to investigate the comparative effectiveness of the administration of one, two, or three medications belonging to the categories of angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), Beta Blockers, Statins, and Metformin, for their potential to delay the clinical onset of AD and provide a window of opportunity for therapeutic intervention.
Retrospective matched case-control study.
Data from the Department of Veterans Affairs national corporate data warehouse.
We conducted an analysis of 122,351 participants (13,611 with AD and 108,740 without AD), aged 65-89, who began at least one of the prescribed medication classes under investigation between October 1998 and April 2018.
We utilized Cox proportional hazard regressions, both with and without propensity score weighting, to estimate hazard ratios (HR) associated with the use of different medication combinations for the pre-symptomatic survival time of AD onset. Additionally, we employed a supervised machine learning algorithm (random forest) to assess the relative importance of various therapies in predicting the occurrence of AD.
Adding Metformin to the combination of ACEI+Beta Blocker (HR = 0.56, 95% CI (0.41, 0.77)) reduced the risk of AD onset compared to ACEI monotherapy alone (HR = 0.91, (0.85, 0.98)), Beta Blocker monotherapy (HR = 0.86, 95% CI (0.80, 0.92)), or combined ACEI+Beta Blocker (HR=0.85, 95%CI (0.77, 0.94)), when statin prescribers were used as a reference. Prescriptions of ARB alone or the combination of ARB with Beta Blocker showed an association with a lower risk of AD onset.
Selected medications for the treatment of multiple chronic conditions among elderly individuals with hypertension, hyperlipidemia, and diabetes as monotherapy or combination therapies lengthen the pre-symptomatic period before the onset of AD.
美国退伍军人事务部（VA）推荐的阿尔茨海默病（AD）药物Leqembi的使用标准包括65岁及以上患有轻度认知障碍（MCI）或轻度AD的患者。这些患者中常见的合并症包括高血压、高脂血症和糖尿病。
我们的目的是研究使用属于血管紧张素受体阻滞剂（ARB）、血管紧张素转换酶抑制剂（ACEI）、β受体阻滞剂、他汀类药物和二甲双胍类别的一种、两种或三种药物给药的相对有效性，以探讨其延迟AD临床发病的可能性，并为治疗干预提供机会窗口。
回顾性匹配病例对照研究。
来自美国退伍军人事务部国家企业数据仓库的数据。
我们对122351名年龄在65 - 89岁之间的参与者进行了分析（13611名患有AD，108740名未患AD），这些参与者在1998年10月至2018年4月期间开始使用至少一种所研究的处方药类别。
我们使用Cox比例风险回归，包括有无倾向得分加权，来估计与使用不同药物组合相关的AD发病前症状出现时间的风险比（HR）。此外，我们采用了一种监督式机器学习算法（随机森林）来评估各种疗法在预测AD发生中的相对重要性。
与单独使用ACEI单药治疗（HR = 0.91，（0.85，0.98））、β受体阻滞剂单药治疗（HR = 0.86，95%CI（0.80，0.92））或联合使用ACEI + β受体阻滞剂（HR = 0.85，95%CI（0.77，0.94））相比，在以他汀类药物处方者作为对照时，将二甲双胍添加到ACEI + β受体阻滞剂组合中（HR = 0.56，95%CI（0.41，0.77））可降低AD发病风险。单独使用ARB或ARB与β受体阻滞剂的组合处方显示与较低的AD发病风险相关。
对于患有高血压、高脂血症和糖尿病的老年人，选择用于治疗多种慢性病的药物作为单药治疗或联合治疗可延长AD发病前的无症状期。
Zotero 插件
