背景:大型前瞻性研究对于调查帕金森病(PD)的环境原因至关重要,但是通过临床检查进行诊断通常是不可行的。
目的:介绍美国女性队列中的病例确定策略和数据收集。
方法:在姐妹研究中(n=50,884,基线年龄55.6±9.0),医师做出的PD诊断首先由参与者或其代理人报告.全队列的后续调查收集了后续诊断的数据,药物使用和PD相关的运动和非运动症状。我们联系了自我报告的PD病例及其治疗医生,以获取相关的诊断和治疗史。诊断裁定是通过对所有可用数据的专家审查做出的,除了非运动症状。我们检查了非运动症状与帕金森病的关系,使用多变量逻辑回归模型和报告的比值比(OR)和95%置信区间(CI).
结果:在确定的371例潜在PD病例中,已确诊242例。与未经证实的病例相比,确诊病例更有可能从多个来源报告PD诊断,药物使用,在随访期间,运动和非运动特征始终如一。PD多基因风险评分与确诊PD相关(ORinter-四分位数=1.74,95%CI:1.45-2.10),但未确诊病例不存在(对应OR=1.05)。低血压,做梦行为,便秘,抑郁症,无法解释的体重减轻,干眼,口干,疲劳与PD风险显著相关,ORs从1.71到4.88。八个阴性对照症状中只有一个与PD事件相关。
结论:研究结果支持我们在这一大型女性队列中的PD病例确定方法。PD前驱表现可能超出其有据可查的范围。
Large prospective studies are essential for investigating the environmental causes of Parkinson\'s disease (PD), but PD diagnosis via clinical exams is often infeasible in such studies.
To present
case ascertainment strategy and data collection in a US cohort of women.
In the Sister Study (n = 50,884, baseline ages 55.6±9.0), physician-made PD diagnoses were first reported by participants or their proxies. Cohort-wide follow-up surveys collected data on subsequent diagnoses, medication usage and PD-relevant motor and nonmotor symptoms. We contacted self-reported PD cases and their treating physicians to obtain relevant diagnostic and treatment history. Diagnostic adjudication was made via expert review of all available data, except nonmotor symptoms. We examined associations of nonmotor symptoms with incident PD, using multivariable logistic regression models and reported odds ratio (OR) and 95% confidence intervals (CI).
Of the 371 potential PD cases identified, 242 diagnoses were confirmed. Compared with unconfirmed cases, confirmed cases were more likely to report PD diagnosis from multiple sources, medication usage, and motor and nonmotor features consistently during the follow-up. PD polygenic risk score was associated with confirmed PD (ORinter-quartile range = 1.74, 95% CI: 1.45-2.10), but not with unconfirmed cases (corresponding OR = 1.05). Hyposmia, dream-enacting behaviors, constipation, depression, unexplained weight loss, dry eyes, dry mouth, and fatigue were significantly related to PD risk, with ORs from 1.71 to 4.88. Only one of the eight negative control symptoms was associated with incident PD.
Findings support our PD
case ascertainment approach in this large cohort of women. PD prodromal presentation is likely beyond its well-documented profile.