Constipation and risk of Parkinson’s disease: A Danish population-based cohort study

https://doi.org/10.1016/j.parkreldis.2016.05.016Get rights and content

Highlights

  • Patients with a diagnosis of constipation were at increased risk of PD.

  • The risk was increased for up to 15 years of follow-up.

  • The effect size was approximately doubled for men for all the follow-up periods.

Abstract

Objectives

To examine long-term associations between constipation and Parkinson’s disease (PD) in men and women, we conducted a population-based cohort study using prospectively collected registry data on hospital contacts for constipation and PD, stratified by follow-up time and sex.

Methods

We linked Danish registries to construct a cohort of all patients in Denmark with an outpatient hospital diagnosis of constipation 1995–2012 and a matched general population comparison cohort. Using Cox regression, we computed hazard ratios (HRs) for PD and corresponding 95% confidence intervals (CIs), adjusting for potential confounders, stratified by sex and follow-up time.

Results

The 31,905 patients with constipation had a higher risk of PD than 159,092 comparison cohort members (adjusted (a) HR = 3.03, 95% CI 2.50–3.66), which was sustained to 11–15 years follow-up (aHR = 3.65, 95% CI 1.67–7.95). Increased risk was apparent in both sexes but stronger in men [aHR = 3.52 (2.67–4.64] than women [aHR = 2.64 (95% CI 2.02–3.44].

Conclusion

In this large population-based cohort study, constipation was associated with sustained increased risk of a PD diagnosis, and the relative risk was higher for men than for women.

Introduction

Non-motor symptoms of Parkinson’s disease (PD), such as REM sleep behavior disorder, depression, and constipation, may antedate cardinal motor symptoms [1], [2], [3]. Starting with the seminal paper by Abbott et al. [4], several prospective observational studies have examined the association between constipation and risk of Parkinson’s disease (reviewed by Adams-Carr et al. [5]). A recent meta-analysis, which included three prospective cohort studies, showed an increased risk of PD (OR = 2.28, 95% confidence interval (CI) 2.10–2.46) among patients with constipation [5]. The risk remained elevated after ten years of follow-up (OR = 2.12, 95% CI 1.76–2.54).

Women experience constipation to a greater extent than men [6]. Two studies have examined possible sex differences for constipation and subsequent risk of PD, with inconsistent results [7], [8], and the previous meta-analyses were not stratified on sex [3], [5]. To determine long-term associations between constipation and PD in men and women, we conducted a population-based cohort study using prospectively collected registry data on hospital contacts for constipation and PD, stratified by follow-up time and sex. The non-motor, preclinical phase of PD may antedate motor manifestations by more than a decade [9], and longer-term follow-up available in Danish registries may help to establish when non-motor symptoms commence.

Section snippets

Constipation and comparison cohorts

Denmark has universal tax-supported health care, including free access to hospital-based care. All residents are assigned a unique personal identification number, registered in the Danish Civil Registration System [10] at birth or upon immigration. This identifier permits unambiguous individual-level linkage among all Danish registries.

We assembled a population-based Danish cohort of all patients aged over 15 years with a first-time outpatient clinic contact for constipation between January 1,

Results

Between 1995 and 2012, 31,905 men and women had an outpatient contact for constipation in Denmark (Table 1). At the index date, the median age of patients and the comparison cohort was 62 years, 44% of subjects in both groups were older than 65 years, and 35% were male. The mean follow-up was 5 years (SD 4.4) for women and 4 years (SD 3.4) for men. Compared with the 159,092 members of the general population comparison cohort, patients with constipation had a higher prevalence of chronic

Discussion

Results from this large, population-based national cohort study corroborate and extend results from previous studies with shorter follow-ups on constipation and PD [3], [5], and from cohort studies with long-term follow-up confined to men [4] or women [8]. We found that patients with a hospital-based outpatient diagnosis of constipation were at increased risk of PD for up to 15 years of follow-up.

Furthermore, we found a higher risk of PD following constipation in men than women. Savica et al.

Author contributions

PB, VH and HTS conceived the idea for the study and developed the study concept and design. ES, EHP and HTS participated in the design of the study and EHP performed the statistical analysis. All authors contributed to the drafting and revision of the manuscript, approved its final version, and agreed to be accountable for all aspects of the work.

Financial disclosures

None of the authors report any conflicts of interests.

Funding sources

The Program for Clinical Research Infrastructure established by the Lundbeck and Novo Nordisk Foundations and from the Aarhus University Research Foundation.

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    Editor's Comment: “Constipation, a non-motor symptom of Parkinsons disease (PD), may antedate motor symptoms. In a population-based cohort study using outpatient hospital diagnosis of constipation and a matched general population comparison cohort in Denmark, Svensson et al showed that subjects with constipation had a higher risk of PD (Hazard ratio 3.03). This risk was sustained in 11–15 years of follow-up. Men had a stronger risk than women, though increased risk was present in both genders. These findings add to the growing body of evidence linking constipation to risk of PD.”

    Eng-King Tan, Associate Editor, Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Outram road, Singapore

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