title: Risk of Parkinson's disease following severe constipation: a nationwide population-based cohort study.
abstract: BACKGROUND
  Constipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample.
  
  
  METHODS
  551,324 participants free of PD, dementia, and stroke were retrospectively ascertained between January 1, 2005 and December 31, 2005 using the Taiwan National Health Insurance Research Database. The association between constipation at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities and concomitant medications use was adjusted in the proportional hazards models.
  
  
  RESULTS
  After an average follow-up of 5.5 years, 2336 incident PD cases were diagnosed. The crude incidence rate of PD per 1,000,000 person-days was 1.57 for subjects without constipation and 4.04, 5.28, and 12.67 for mild, moderate, and severe constipation, respectively. After adjusting for age, sex, comorbidities, and concomitant medication use, patients with constipation were more likely to develop PD than subjects without constipation; the adjusted hazard ratio (aHR) was 3.28 (95% CI: 2.14-5.03), 3.83 (2.51-5.84), and 4.22 (2.95-6.05) for individual constipation severity categories. Constipation severity was also associated with an increased likelihood of PD in the time-varying analysis; the aHR was 2.84 (2.43-3.33), 5.22 (4.61-5.92), and 10.47 (9.46-11.58) for mild, moderate, and severe constipation, respectively (P < 0.0001). After excluding PD patients diagnosed within 3 years of constipation, the association remained significant.
  
  
  CONCLUSIONS
  Our study suggests that the severity of constipation is associated with a future diagnosis of PD in a dose-dependent manner.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chin-Hsien
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Cardiovascular Center, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Yun-Lin County, Taiwan.
authors.forename: Jou-Wei
authors.initials: JW
authors.lastname: Lin
authors.affiliation: Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: chiahsuin123@yahoo.com.tw.
authors.forename: Chia-Hsuin
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: robinwu@ntu.edu.tw.
authors.forename: Ruey-Meei
authors.initials: RM
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018672:Community Health Planning; D003248:Constipation / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009313:National Health Programs / Q000706:statistics & numerical data; D010300:Parkinson Disease / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
keywords: Constipation; Non-motor symptoms; Parkinson's disease; Population study; Pre-motor symptoms