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.
Asymmetry of dopaminergic neurodegeneration and subsequent lateralisation of motor symptoms are distinctive features of Parkinson's disease compared to other forms of neurodegenerative or symptomatic parkinsonism. Even 200 years after the first description of the disease, the underlying causes for this striking clinicopathological feature are not yet fully understood. There is increasing evidence that lateralisation of disease is due to a complex interplay of hereditary and environmental factors that are reflected not only in the concept of dominant hemispheres and handedness but also in specific susceptibilities of neuronal subpopulations within the substantia nigra. As a consequence, not only the obvious lateralisation of motor symptoms occurs but also patterns of associated non-motor signs are defined, which include cognitive functions, sleep behaviour or olfaction. Better understanding of the mechanisms contributing to lateralisation of neurodegeneration and the resulting patterns of clinical phenotypes based on bilateral post-mortem brain analyses and clinical studies focusing on right/left hemispheric symptom origin will help to develop more targeted therapeutic approaches, taking into account subtypes of PD as a heterogeneous disorder.
At the early IPD stage there are marked deficits of LOV performances, while HOV performances are still intact, with the exception of reduced recognition of "sadness". At this stage, IPD patients seem still to compensate the deficient input of low contrast sensitivity, known to be pivotal for appreciation of negative facial emotions and confirmed as such for healthy controls in this study.
The objective of this study was to evaluate the discriminative power of different nonmotor signs for early diagnosis of Parkinson's disease (PD). Thirty patients with PD with
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