Frozen Shoulder and the Risk of Parkinson’s Disease: A Danish Registry-Based Cohort Study

Abstract

Background

Frozen shoulder may be an early preclinical symptom of Parkinson’s disease (PD).

Objective

To examine PD risk after frozen shoulder diagnosis and to evaluate this disorder as a possible manifestation of parkinsonism preceding the clinical recognition of PD and possible target for screening.

Methods

Danish population-based medical registries were used to identify patients aged ≥40 years with a first-time frozen shoulder diagnosis (1995–2016). A comparison cohort was randomly selected from the general population matched on age and sex. To address detection bias and the specificity of frozen shoulder diagnosis, we performed a sensitivity analysis, using similar matching criteria to select a cohort of patients with back pain diagnosis. The outcome was incident PD. Cumulative incidences and adjusted hazard ratios (HRs) were estimated with 95% confidence intervals (CIs).

Results

We identified 37,041 individuals with frozen shoulder, 370,410 general population comparators, and 111,101 back pain comparators. The cumulative incidence of PD at 0–22 years follow-up was 1.51% in the frozen shoulder cohort, 1.03% in the general population cohort, and 1.32% in the back pain cohort. For frozen shoulder versus general population, adjusted HRs were 1.94 (CI: 1.20–3.13) at 0–1 years and 1.45 (CI: 1.24–1.70) at 0–22 years follow-up. For frozen shoulder versus back pain, adjusted HRs were 0.89 (CI: 0.54–1.46) and 1.01 (CI: 0.84–1.21), respectively.

Conclusion

Patients with frozen shoulder had an increased PD risk compared with the general population, although the absolute risks were low. Frozen shoulder might sometimes represent early manifestations of PD. Detection bias probably cannot account for the increased PD risk during the long-term follow-up.

Keywords:

• adhesive capsulitis
• back pain
• cohort studies
• frozen shoulder
• Parkinson disease

Abbreviations

PD, Parkinson’s disease; DNPR, The Danish National Patient Registry; DCRS, The Danish Civil Registration System; ICD-8, The International Classification of Disease 8th Edition; ICD-10, The International Classification of Disease 10th edition; PYRs, Person years; HR, Hazard ratio; CI, Confidence interval.

Data Sharing Statement

To protect the privacy of patients, it is by Danish law prohibited to make individual-level data publicly available.

Ethics

Patient consent is not required by Danish law for studies based on routine electronic data. The study was reported to the Danish Data Protection Agency through registration at Aarhus University (record number: AU-2016-051-000001, sequential number 818).

Acknowledgments

We gratefully acknowledge Clinical Professor and Chair Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, for his valuable contributions to and critical review of this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

NRG, KV, and ABP are salaried employees at Aarhus University or Aarhus University Hospital. VWH is a salaried employee at Stanford University. VWH also received honoraria from the Institute for Clinical and Economic Review (reviewer), Kansas University Alzheimer’s Disease Research Center (advisory board member), and the University of Oregon Health Sciences University (speaker). In addition, VWH received research support from other NIH grants as principal investigator or co-investigator (including NIH-prime grants from the Universities of Kentucky, Pennsylvania, Southern California, Wisconsin, and Washington); and from Health IQ Insurance. VWH received travel reimbursements from the Alzheimer’s Disease Cooperative Study and Aarhus University. For grants received over the last 12 months, NRG has received grants from Familien Hede Nielsens Fond, William Demant Fonden, Frimodt-Heineke Fonden, Dansk Ortopædkirurgisk Selskabs Fond, Helga og Peter Kornings Fond, and Aarhus University, with no relation to this study. The authors have no disclosures regarding stock ownership in medically related fields, intellectual property rights, consultancies, expert testimony, partnerships, inventions, contracts, royalties or patents. The authors report no other conflicts of interest in this work.

Additional information

Funding

VWH’s effort for this study was supported by the National Institutes of Health (NIH) grant P30 AG066515. There was no further dedicated funding for the preparation of this manuscript.