Shahela Akhand Laboni
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Urinary Incontinence among Parkinson’s Disease Patients in Alberta: Incidence and Risk Predictors by Shahela Akhand Laboni A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science In Epidemiology School of Public Health University of Alberta © Shahela Akhand Laboni, 2020 Abstract Background: Parkinson’s disease (PD) is one of the most common neurological chronic diseases among older adults in Canada. More than 100,000 Canadians are diagnosed with PD with an annual incidence of 20 new cases (per 100,000 people). Urinary incontinence (UI) is one of the common non-motor symptoms of PD that significantly affect health-related quality of life. Approximately 55% of Canadians diagnosed with PD have reported UI, yet there is limited research that has examined UI in PD within the Canadian population context. Objectives: We estimated the incidence rate and cumulative incidence of UI among PD patients aged ≥ 45 years within the first five years of their PD diagnosis in Alberta. We also investigated age, sex, and Charlson comorbidity index (CCI) score as predictive risk factors of developing UI in PD patients. Methods: A retrospective cohort (2004 - 2014) of PD cases ≥ 45 years with incident UI was assembled using provincial health administrative databases (physician’s claim, inpatient, ambulatory, and drug files) of Alberta. Incidence rate and cumulative incidence of UI among PD patients were estimated over the follow-up years and stratified by age and sex. Cox proportional hazard regression was used to evaluate the associated risk predictors of UI in PD. Results: Among 9,540 PD patients aged 45 years or older in Alberta, a total of 1,253 UI incident cases were identified among them anytime between 2004 to 2014 study period. Within the study period (2004-2014), after following the PD patients for the first 5 years post PD diagnosis, a total of 1,159 incident UI cases were identified among them. Among these cases, 41.8% (21.7% male and 20.0% female) of UI cases belong to age group 75-84 years. ii The crude incidence rate of UI in PD patients was 17.8 per 1,000 person-years and the observed highest incidence rate (37.1 per 1,000 person-years) belonged to the age group 75-84 years. The overall cumulative incidence of UI among all PD patients was 3.8% (95% CI 0.03- 0.04) at the sixth month and 14.7% (95% CI 0.14-0.16) at the fifth year. PD patients with UI aged 75-84 years had the highest cumulative incidence (16.2%, 95% CI 0.15-0.18). The cumulative incidence of female patients was comparatively higher than male patients of all ages. At the fifth-year post PD diagnosis, the estimated cumulative incidence of males and females was 13.7% (95% CI 0.13-0.15) and 16.0% (95% CI 0.15-0.17), respectively. After an adjustment for age, the female-to-male standardized cumulative incidence also showed a significantly higher cumulative incidence of UI in females aged 75-84 years throughout the follow-up years. Hazard ratios (HR) were estimated using age, sex, and CCI score predictor variables in the regression model. Age groups (45-54: reference, 55-64: multivariate-adjusted HR 1.74, 95% CI 1.23-2.45, 65-74: multivariate-adjusted HR 1.84, 95% CI 1.32-2.56, 75-84: multivariate- adjusted HR 2.08, 95% CI 1.50-2.87 and ≥85: multivariate-adjusted HR 1.66, 95% CI 1.17- 2.34), sex (male: reference, female: multivariate-adjusted HR 1.24, 95% CI 1.04-1.39), and CCI score (multivariate-adjusted HR 1.04, 95% CI 1.01-1.06) were significantly associated with the development of UI within the first five years of diagnosis of PD. PD patients who belonged to the age group 74-84 years showed a two-fold increased risk of developing UI (multivariate- adjusted HR:2.08, 95% CI 1.50-2.87). The predicted risk of developing UI among PD patients was 1.2 times higher in females. For each 1-point increase in CCI score, there was a 4% greater risk of developing UI in PD individuals. Conclusion: With the advancement of age, UI incidence among PD patients in Alberta increased, especially in patients aged 75-84 years, and was consistently higher in females. iii However, further nationwide research is needed with a longer follow-up period to better understand the burden of UI in PD patients. We believe that our study will provide valuable information concerning the Canadian PD population diagnosed with UI and will influence future studies to address this important health topic. iv Preface This thesis is an original work by Shahela Akhand Laboni. No part of this thesis has been previously published. v Acknowledgments I would like to appreciate and express my gratitude to my thesis supervisor Professor Dr. Don Voaklander. It was my privilege to work under such an expert and knowledgeable person. I would also like to thank Dr. Allyson Jones for her valuable suggestions towards my work. Without their continuous monitoring and reviewing, it would not be possible to complete this thesis. My special gratitude goes to Dr. Jason Randall for his valued contribution. In addition, I would like to express my sincere gratitude and appreciation to Dr. Wayne Martin for being the external examiner. I am also grateful to my family for their continuous support and love. vi Table of contents Abstract ................................................................................................................ ii Preface .................................................................................................................. v Acknowledgments ............................................................................................... vi List of tables ....................................................................................................... xii List of figures .................................................................................................... xiii List of abbreviations ......................................................................................... xiv Chapter 1: Introduction ...................................................................................... 1 1.1 Overview ......................................................................................................... 1 1.2 Statement of the Problem .............................................................................. 2 1.3 Aim and Objective ......................................................................................... 3 1.4 Research Hypothesis and Question ............................................................... 4 1.5 Significance ..................................................................................................... 4 1.6 Thesis Outline ................................................................................................. 5 Chapter 2: Literature Review ............................................................................. 6 2.1 Background .................................................................................................... 6 2.2 Urinary Incontinence ..................................................................................... 7 2.2.1 Epidemiology of Urinary Incontinence ........................................................................8 vii 2.2.2 Overview of the Micturition Reflex ..............................................................................8 2.2.3 Risk Factors for Urinary Incontinence ........................................................................9 2.2.4 Types of Urinary Incontinence ................................................................................... 11 2.2.5 Treatment of Urinary Incontinence ........................................................................... 12 2.3 Parkinson’s Disease.......................................................................................14 2.3.1 Overview of Disease Pathology ................................................................................... 14 2.3.2 Epidemiology of Parkinson’s Disease ......................................................................... 15 2.4 Epidemiology of Urinary Incontinence in Parkinson’s Disease..................16 2.5 Clinical Background: Urinary Incontinence in Parkinson’s Disease .........18 2.6 Symptomatic Features of Urinary Incontinence in Parkinson’s Disease ...19 2.7 Possible Neurogenic Mechanisms of Urinary Incontinence in Parkinson’s Disease .................................................................................................................20 2.8 Limitations and Challenges of Identification of Urinary Incontinence Cases in Parkinson’s Disease Using Administrative Data ................................23 Chapter 3: Method ..............................................................................................25 3.1 Study Population ...........................................................................................25 3.2 Study Design ..................................................................................................25 3.4 Study Measures .............................................................................................28 viii 3.4.1 Parkinson’s Disease: Case Definition ......................................................................... 28 3.4.2 Urinary Incontinence: Case Definition ...................................................................... 29 3.4.3 Urinary Incontinence in Parkinson’s Disease: Incident Case Cohort....................... 32 3.4.6 Charlson Comorbidity Index Score Calculation........................................................ 32 3. 5 Statistical