Antidementia medication use, safety, and effectiveness among nursing home residents with Alzheimer's disease

项目摘要/摘要 本提案是对PA-17-088的响应。据预测，患有阿尔茨海默病的美国人的数量 从2019年的560万增加到2050年的1380万，翻了一番以上。阿尔茨海默病患病率的上升 这是一个严重的公共卫生问题。2019年，阿尔茨海默病估计排在第六位 死因在美国排在第四位，残疾原因调整后失去的寿命年。一半的护理工作 家庭人口被诊断出患有阿尔茨海默病或其他痴呆症。只有两个可用的类 药物、胆碱酯酶抑制剂(ChEIs)和美金刚已被证明可以减缓症状 阿尔茨海默病的进展。多奈哌齐(最广泛使用的CHEI)有FDA的适应症， 中度和重度阿尔茨海默病，而美金刚用于中度到重度阿尔茨海默氏症 并有证据支持在轻度疾病中可能的益处。只有40%的居民接受了治疗 历史上在疗养院入院时有两种药物类别(2006年)，以及一小部分人(10%) 接受综合治疗。疗养院居民发生药物不良事件的风险可能更高- 由于多药并存的高负担，药物和药物-疾病的相互作用。然而在多米诺骨牌里 在社区居住患者中进行的临床试验，在结束阶段前停止CHEI 这种疾病与较差的临床结果有关。近四分之一的疗养院居民接受了 入院时有CHEIs和/或美金胺的患者在入院后不久停止治疗(无论 痴呆症严重程度)，并有临床恶化的潜在风险，需要使用更危险的药物 抗精神病药物等药物。使用同期的、国家的、联邦授权的最低数据集3.0 与联邦医疗保险A部分和D部分索赔相关的研究目的是：1)检查当代CHEI的模式， 美金刚和精神药物在患有阿尔茨海默病的NH居民中的使用；2)比较长期 开始联合治疗、单一治疗和NO治疗的居民之间的有效性、安全性和存活率 使用CHEIs和美金胺治疗；以及3)识别居民特征(例如，剂量、共存条件， 同时服药，痴呆期)，使用CHEIs和/或美金刚治疗可获得净临床疗效 利益。拟议的R01是对对CHEIs和美金刚进行精心设计的长期研究的呼吁的回应。 通过扩大证据库，促进以居民为中心的动态决策过程 在老年疗养院人群中治疗阿尔茨海默氏症，这项建议实现了国家 计划解决阿尔茨海默氏症，以有效治疗阿尔茨海默氏症，并优化护理质量和 效率。这项研究也与国家老龄研究所的战略目标密切相关，以改善 药物的安全使用。

PROJECT SUMMARY/ABSTRACT This proposal is responsive to PA-17-088. The number of Americans living with Alzheimer’s disease is projected to more than double from 5.6 million in 2019 to 13.8 million by 2050. This rise in Alzheimer’s disease prevalence represents a serious public health concern. In 2019, Alzheimer’s disease was estimated to be the sixth leading cause of death in the US and the fourth leading cause of disability adjusted life years lost. Half of the nursing home population has a diagnosis of Alzheimer’s disease or another dementia. Only two available classes of medications, cholinesterase inhibitors (ChEIs) and memantine have been demonstrated to slow symptomatic progression of Alzheimer’s disease. Donepezil (the most widely used ChEI) has FDA indications for mild, moderate, and severe Alzheimer’s disease, while memantine is indicated for moderate to severe Alzheimer’s disease and has evidence supporting possible benefits in mild disease. Only ~40% of residents were treated with either medication class at the time of nursing home admission historically (2006), and a small minority (10%) received combination therapy. Nursing home residents may be at higher risk for adverse drug events from drug- drug and drug-disease interactions due to a high burden of polypharmacy and comorbidities. Yet in the DOMINO clinical trial conducted among community dwelling patients, discontinuation of a ChEI before the end stages of the disease was associated with worse clinical outcomes. Nearly a quarter of nursing home residents treated with ChEIs and/or memantine at the time of admission discontinued treatment shortly after admission (regardless of dementia severity) and were potentially at risk for clinical worsening and the need to use more hazardous drugs such as antipsychotics. Using contemporaneous, national, federally-mandated Minimum Data Set 3.0 linked to Medicare Part A and D claims, study aims are to: 1) examine contemporary patterns of ChEI, memantine, and psychotropic medication use in NH residents with Alzheimer’s disease; 2) compare long-term effectiveness, safety, and survival between residents initiating combination therapy, monotherapy, and no treatment with ChEIs and memantine; and 3) identify resident characteristics (e.g., dosing, comorbid conditions, concurrent medications, dementia stage) for whom treatment with ChEIs and/or memantine confers a net clinical benefit. The proposed R01 is responsive to calls for well-designed long-term studies of ChEIs and memantine. By expanding the evidence base to facilitate a dynamic resident-centered decision-making process regarding Alzheimer’s disease treatment in an aged nursing home population, this proposal fulfills the goals of The National Plan to Address Alzheimer’s Disease to effectively treat Alzheimer’s disease and to optimize care quality and efficiency. This research is also closely aligned with the National Institute on Aging’s Strategic Goal to improve the safe use of medications.