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

项目概要/摘要 本提案响应PA-17-088。据预测，美国患有阿尔茨海默病的人数 从2019年的560万增加到2050年的1380万。老年痴呆症患病率的上升 是一个严重的公共卫生问题。2019年，阿尔茨海默病估计是第六大疾病 是美国的第四大死因，也是残疾调整寿命年损失的第四大原因。一半的护理 家庭人口被诊断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（ChEI）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）具有FDA适应症， 中度和重度阿尔茨海默病，而美金刚胺适用于中度至重度阿尔茨海默病 并有证据支持对轻度疾病的可能益处。只有约40%的居民接受了治疗 在历史上（2006年），在疗养院入院时使用任何一种药物，少数（10%） 接受了联合治疗疗养院的居民可能有更高的风险发生药物不良事件， 由于多种药物和合并症的高负担，药物和药物-疾病相互作用。在DOMINO 在社区居住患者中进行的临床试验，在 该疾病与更差的临床结果相关。近四分之一的养老院居民接受了治疗 在入院时使用ChEI和/或美金刚的患者在入院后不久停止治疗（无论 痴呆的严重程度），并有潜在的风险，临床恶化，需要使用更危险的 药物，如抗精神病药。使用同期的、国家的、联邦规定的最小数据集3.0 与医疗保险A部分和D部分索赔有关，研究目的是：1）检查ChEI的当代模式， 美金刚和精神药物的使用在NH居民与阿尔茨海默病; 2）比较长期 开始联合治疗、单药治疗和不开始联合治疗的住院医师之间的有效性、安全性和生存率 用ChEI和美金刚治疗;和3）鉴定常驻特征（例如，给药、合并症， 合并用药，痴呆阶段），对于这些患者，ChEI和/或美金刚治疗可提供净临床疗效 效益拟议的R 01是响应呼吁精心设计的长期研究ChEI和美金刚胺。 通过扩大证据基础，促进以居民为中心的动态决策过程， 老年疗养院人群中阿尔茨海默病的治疗，该提案实现了国家 计划解决阿尔茨海默病，以有效治疗阿尔茨海默病，并优化护理质量， 效率这项研究也与国家老龄化研究所的战略目标密切相关， 安全使用药物。

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.