Parkinson's Disease Case Ascertainment in the Sister Study: A Cohort for Environmental Health Research

Zichun Cao, Shengfang Song, Xuemei Huang, Chenxi Li, Zhehui Luo, Aimee A. D'Aloisio, Lourdes Suarez, Dena G. Hernandez, Andrew B. Singleton, Dale P. Sandler, Honglei Chen

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Abstract

Background: 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. Objective: To present case ascertainment strategy and data collection in a US cohort of women. Methods: 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). Results: 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. Conclusion: Findings support our PD case ascertainment approach in this large cohort of women. PD prodromal presentation is likely beyond its well-documented profile.

Original languageEnglish (US)
Pages (from-to)729-742
Number of pages14
JournalJournal of Parkinson's Disease
Volume13
Issue number5
DOIs
StatePublished - 2023

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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