Impact of Anticholinergic and Dopamine Receptor Blocking Drug Exposure on Parkinson Disease Trajectory and Outcomes

项目总结/摘要 认知障碍和福尔斯导致髋部骨折是住院和死亡的主要原因 帕金森病（PD）是一种神经系统疾病，主要影响生长最快的 美国人口（老年人）。预防福尔斯或延迟PD患者痴呆的发作将 对公众健康有重大影响。具有抗胆碱能（ACH）作用或多巴胺受体的药物 阻断（DRB）活动已被证明会损害步态，导致认知功能障碍，加速 痴呆症的进展和死亡率的增加。帕金森病患者特别容易受到 由于PD相关的中枢多巴胺能和胆碱能干扰导致ACH和DRB药物的不良反应 途径。此外，PD药物治疗试验使用步态和认知作为疾病进展的标志物 不考虑ACH或DRB负担。然而，没有临床指南限制ACH或DRB药物的使用 存在，代表了本修订提案将解决的知识方面的根本差距。 我们计划使用医疗保险处方、临床和使用数据以及来自 PD患者的纵向队列研究，以确定可预防的药物决定因素 PD中的不良健康结局和不可靠的临床试验终点。本研究将（1）产生非常有用的 PD处方变化的基准数据和2）解决关键的临床问题-比较安全性 在PD中具有ACH和DRB潜力的药物的治疗替代品中。我们期望 通过为临床指南提供强有力的证据基础，从根本上推进临床神经病学领域 以及与PD中ACH和DRB负担相关的护理质量指标。我们的研究结果也会对 翻译影响，因为定义ACH药物对疾病轨迹研究测量的影响 临床结果将改变未来PD神经保护药物试验的数据收集和分析策略， 提高此类试验识别有效药物的能力。我们还直接解决一个优先事项 2014年NINDS帕金森病研究议程的建议：“确定 促进卫生服务干预“-结合定性和定量数据，产生新的见解 转化为潜在的可预防的PD结果，直接转化为政策举措。

Project Summary/Abstract Cognitive impairment and falls leading to hip fracture are leading causes of institutionalization and mortality in Parkinson disease (PD), a neurological disorder which predominantly affects the most rapidly growing segment of the U.S. population (older adults). Preventing falls or delaying the onset of dementia in PD would have a substantial public health impact. Drugs with anticholinergic (ACH) effects or dopamine receptor blocking (DRB) activity have been demonstrated to impair gait, cause cognitive dysfunction, hasten the progression of dementia and increase mortality. Parkinson disease patients are particularly vulnerable to adverse effects of ACH and DRB drugs due to PD-related disruption of central dopaminergic and cholinergic pathways. Furthermore, PD pharmacotherapy trials use gait and cognition as markers of disease progression without considering ACH or DRB burden. Yet, no clinical guidelines limiting the use of ACH or DRB drugs exist, representing a fundamental gap in knowledge this revised proposal will address. We plan to use Medicare prescription, clinical, and utilization data and rich clinical research data from a longitudinal cohort study of individuals with PD to identify the pharmacological determinants of preventable adverse health outcomes and unreliable clinical trial endpoints in PD. This study will 1) produce highly useful benchmark data on variation in prescribing in PD and 2) address a crucial clinical issue—comparative safety among therapeutic alternatives for medications with ACH and DRB potential in PD. We expect to fundamentally advance the field of clinical neurology by providing a strong evidence base for clinical guidelines and care quality indicators related to ACH and DRB burden in PD. Our results will also have a positive translational impact because defining the impact of ACH drugs on research measurements of disease trajectory and clinical outcomes will alter data collection and analysis strategies for future PD neuroprotective drug trials, improving the ability of such trials to identify effective drugs. We also directly address a priority recommendation from the 2014 NINDS Parkinson's Disease Research Agenda: `to determine factors that facilitate health services interventions'- by combining qualitative and quantitative data to produce new insights into potentially preventable outcomes in PD that directly translate into policy initiatives.