Abstract :
[en] Functional mobility is one of the disease-related features most relevant to people with PD (Bowring et al., 2022). It worsens as the disease progresses (Lindh-Rengifo et al., 2021, Mirelman et al., 2019) resulting in increasing professional care and nursing home costs (Chaudhuri et al., 2024). A promotion of mobility and functionality could help to delay institutionalisation and respect the desire of people with PD to remain in their homes (Habermann and Shin, 2017). This dissertation aimed to understand determinants of functional mobility, the phenomenon of unexpectedly stable trajectories for functional mobility and their experience in people with PD. CHAPTER ONE introduces the impaired functional mobility in Parkinson’s disease, life with a chronic disease, longitudinal data analysis of the Luxembourg Parkinson’s Study, the mixed-methods design and the involvement of individuals with PD in the dissertation. Using data from the Luxembourg Parkinson’s study, a nationwide, observational, longitudinal-prospective and dynamic cohort, CHAPTER TWO reports the assessment of convergent and discriminative validity of the Functional Mobility Composite Score (FMCS). The FMCS is an algorithm based on the Parkinson’s Disease Questionnaire-39 (PDQ-39) to assess patient-reported functional mobility in a multilingual context of Luxembourg. To get an overview of the current state of research, CHAPTER THREE reports a systematic review concluding future research on patient-reported functional mobility should focus among other on environmental factors as determinants. In preparation of the longitudinal analyses, CHAPTER FOUR demonstrates in a comparative analysis, how the choice of statistical method may influence research outcomes. Using the previously established and validated methodology, CHAPTER FIVE applies linear mixed-effects models to deal with the differential trajectories of patient-reported functional mobility and the motor- and nonmotor symptoms in men and women with PD. An overall slower disease progression was observed in women compared to men. As the development of Parkinson’s disease (PD) is influenced by genetic and environmental factors and the role of PD-risk GBA1 variants is not yet well understood, CHAPTER SIX compares the progression of patient-reported functional mobility and other symptoms in individuals with different genetic GBA1 variants (Gaucher-related or PD-risk GBA1 variants) and the non-carriers. The GBA1-variants were not associated with a slower decline of patient-reported functional mobility. Nevertheless, a reevaluation of their pathologic relevance would be warranted if these findings are confirmed in an independent cohort due to the described effect modification of the nonmotor symptoms. To better understand the phenomenon of unexpectedly stable trajectories of functional mobility and the protective factors involved, CHAPTER SEVEN reports a sequential explanatory mixed-methods study. First mixed effects models investigated the effect modification of relational (partner, children), cognitive (educational attainment), and socioeconomic (place of residence) reserves on the trajectory of patient-reported functional mobility. Then qualitative semi-structured interviews with participants experiencing an unexpectedly stable trajectory of functional mobility explored their perceptions of barriers and facilitators related to those reserves. Characteristics of individuals with unexpectedly stable trajectories of patient-reported functional mobility that emerged from the inductive analysis were psychosocial factors similar to self-efficacy, chronic inflammatory diseases and self-care activities promoting a physically active lifestyle. Finally, CHAPTER EIGHT of this dissertation synthesises and discusses the results of all chapters, the methodological considerations and presents future directions and the overall conclusions of this dissertation.
