The Luxembourg Parkinson’s Study: A Comprehensive Approach for Stratification and Early Diagnosis

Abstract

While genetic advances have successfully defined part of the complexity in Parkinson’s disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies typically include patients with earlier disease stages and exclude comorbidities, thus ignoring a substantial part of the real-world PD population. To account for these limitations, we implemented the Luxembourg PD study as a comprehensive clinical, molecular and device-based approach including patients with typical PD and atypical parkinsonism, irrespective of their disease stage, age, comorbidities, or linguistic background. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, we implemented an open-source digital platform that can be harmonized with international PD cohort studies. Our interests also reflect Luxembourg-specific areas of PD research, including vision, gait, and cognition. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies. We provide evidence for the feasibility of such a cohort program with deep phenotyping and high quality biosampling on parkinsonism in an environment with structural specificities and alert the international research community to our willingness to collaborate with other centers. The combination of advanced clinical phenotyping approaches including device-based assessment will create a comprehensive assessment of the disease and its variants, its interaction with comorbidities and its progression. We envision the Luxembourg Parkinson’s study as an important research platform for defining early diagnosis and progression markers that translate into stratified treatment approaches.

Parkinson’s disease-associated alterations of the gut microbiome can invoke disease-relevant metabolic changes

“…The Luxembourg Parkinson’s Disease study includes patients with typical PD and atypical parkinsonism, as well as matched healthy control subjects from Luxembourg and its neighbouring regions from a broad age-range (Hipp et al 2018). For the present study, we focused on typical PD patients and healthy controls over the age of 50 (Table 1, Methods).…”

“…For this study, data and biospecimen of the LuxPark cohort were utilised (Hipp et al 2018). The Luxembourg Parkinson’s study includes a variegated group of patients with typical PD and atypical parkinsonism, and controls from Luxembourg and its neighbouring regions (Hipp et al 2018). Controls were partly sampled among relatives of patients.…”

“…All study participants gave written informed consents, and the study was performed in accordance with the Declaration of Helsinki. The LuxPark study (Hipp et al 2018) was approved by the National Ethics Board (CNER Ref: 201407/13) and Data Protection Committee (CNPD Ref: 446/2017).…”

“…In the present study, we aim at investigating microbial changes associated with PD while focusing on possible covariates influencing microbial composition and at proposing functional, i.e., metabolic, consequences arising from the microbiome changes. First, we analysed the faecal microbial composition of PD patients and controls from the Luxembourg Parkinson’s study (Hipp et al 2018) (Figure 1). Second, based on the observed significant differences in the composition of microbial communities between PD patients and controls, we created and interrogated personalised computational models representing the metabolism of each individual’s microbial community.…”

Update of the MDS research criteria for prodromal Parkinson's disease

“…67 Heterogeneity of prodromal states should be further investigated and may be important for targeted trial recruitment. 68 In summary, this Update of the MDS Research Criteria for Prodromal PD aims to encourage further research in prodromal PD, in particular, regarding prospective studies of promising candidate markers. Further validation and testing of the criteria and future revisions will be needed to continually improve the diagnostic sensitivity and specificity of the criteria.…”