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

项目摘要/摘要 认知障碍和跌倒导致髋部骨折是导致住院和死亡的主要原因。 在帕金森病(PD)中，一种神经疾病，主要影响发展最快的 美国人口的一部分(老年人)。预防跌倒或延缓帕金森病患者痴呆的发病 对公共卫生有重大影响。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患上 帕金森病相关中枢多巴胺能和胆碱能障碍所致ACH和DRB药物的不良反应 小路。此外，帕金森病药物治疗试验使用步态和认知作为疾病进展的标志 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，这是这项修订提案将解决的知识方面的根本差距。 我们计划使用Medicare处方、临床和利用数据以及来自 帕金森病患者的纵向队列研究以确定可预防的药理学决定因素 帕金森病患者的不良健康结局和不可靠的临床试验终点。这项研究将产生非常有用的成果 帕金森病患者处方变化的基准数据和2)解决了一个关键的临床问题-相对安全性 在帕金森病患者ACH和DRB潜力药物的治疗选择中。我们希望 为临床指南提供强有力的证据基础，从根本上促进临床神经病学领域的发展 与帕金森病患者ACH和DRB负担相关的护理质量指标。我们的结果也将有积极的 翻译影响，因为定义ACH药物对疾病轨迹的研究测量的影响 临床结果将改变未来帕金森病神经保护药物试验的数据收集和分析策略， 提高此类试验确定有效药物的能力。我们还直接解决了一个优先事项 来自2014年NINDS帕金森氏病研究议程的建议：‘确定 促进卫生服务干预--将定性和定量数据结合起来，产生新的见解 转化为帕金森病潜在的可预防结果，直接转化为政策倡议。

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.