Identifying early cognitive patterns in Parkinson’s disease

First large-scale analysis of the Luxembourg Parkinson’s Study

Since 2015, more than 800 people with Parkinson’s disease or other forms of parkinsonism and over 800 healthy controls have participated in the Luxembourg Parkinson’s Study in the frame of National Centre of Excellence in Research on Parkinson’s Disease (NCER-PD) led by Prof. Dr. Rejko Krüger. Participants underwent detailed neurological examinations, neuropsychological tests, and donated multiple body fluids for further molecular and genetic analysis. While people with Parkinson’s were invited to attend annual follow up examinations to gain a detailed insight into the course of the disease, healthy controls were examined every 4 years. More than 20 researchers from the Luxembourg Institute of Health, the Luxembourg Centre for Systems Biomedicine of the University of Luxembourg and the Centre Hospitalier de Luxembourg have contributed to the first comprehensive analysis of the data, which was recently published in the open-access scientific journal Frontiers in Neurology.

Today we talk to Dr. med. Lukas Pavelka, clinician-scientist and neurologist in training, who is one of the first authors of this study:

Dr. Pavelka, what are the aims of the Luxembourg Parkinson’s Study?

Parkinson’s disease is the second most common neurodegenerative disease and the number of patients is expected to dramatically increase in the coming years. A major concern with Parkinson’s disease is that it is usually diagnosed when the disease has already progressed significantly and motor symptoms are apparent. The overall aim of this longitudinal programme was to gain a better understanding of the disease, which will ultimately allow the identification of new methods for the early diagnosis and treatment. Additionally, the spectrum of symptoms in people with Parkinson’s is highly variable and further research is needed to investigate whether multiple subtypes of Parkinson’s disease exist and what lays behind these important differences.

Can you explain what a baseline statistical analysis is and why this is important?

The essence of the clinical research project is to compare the results of the data from the first visit from all people with Parkinson’s and healthy volunteers we have collected at Parkinson’s Research Clinic between 2015-2021. Differences between the patients with different forms of parkinsonism (such as Parkinson’s disease and progressive supranuclear palsy, an atypical form of parkinsonism) and healthy controls can reveal important information that can lead to the discovery of disease patterns. In the future, these findings can then lead to the development of new diagnostic tests or therapeutic approaches that can improve current treatment or diagnosis of the neurodegenerative disorders.

In our baseline analysis, we were looking at many different epidemiological and clinical characteristics between the studied groups. We analysed the profiles of 1648 individuals included in the Luxembourg Parkinson’s study baseline dataset, making it one of the largest single-center study of a kind. It could hence be seen as a very first and comprehensive description of people with Parkinson’s in Luxembourg, highlighting the differences in various aspects of neurodegeneration between the groups.

What are the main findings from the baseline statistical analysis?

When shading light on the differences between the three largest groups of individuals in our cohort, that is Parkinson’s, progressive supranuclear palsy (PSP) and healthy controls, we identified unexpectedly high frequency of loss of smell (hyposmia) in people with progressive supranuclear palsy (PSP). So far it has always been supposed that hyposmia was highly specific for Parkinson’s disease but was not typical for people with atypical forms of parkinsonism, especially PSP. Thus, our study, which analysed a larger number of people with PSP compared to many earlier studies, challenges this current view on lack of hyposmia in PSP.

In addition, we also looked at environmental factors in the context of Parkinson’s disease. For instance, we found a higher rate of occupational use of pesticides in people with Parkinson’s compared to controls in Luxembourg. Moreover, we found alcohol abstinence to be significantly higher in people with Parkinson’s disease compared to controls. One of the explanations for this finding could be the fact that dopamine is known to play crucial role in addiction behaviour. Therefore, the reduction of dopamine levels due to neurodegeneration in Parkinson’s may be responsible for a reduced risk for addictive behaviour, here leading to alcohol abstinence. However, further research is warranted to better understand the link the between those environmental factors and Parkinson’s and we hope to contribute to this knowledge gain through further analysis of the Luxembourg Parkinson’s Study.

What else are the plans for the future?

Our baseline analysis is just the beginning. We are currently analysing many different aspects of this clinically and biologically characterised cohorts in more detail, so further findings and discoveries advancing the research on neurodegeneration are to be expected soon. The baseline analysis is also an important source of information for the international Parkinson’s research community, as it allows other researchers to collaborate on the wealth of data that is available in Luxembourg and cross-validate the findings in the independent cohorts. After all, the fight against Parkinson’s disease is a global one, and we regularly collaborate with researchers and clinicians from abroad by pooling data or samples to analyse specific aspects in several cohorts together. This way, we have an even larger numbers of participants, which allows us to study smaller details with better accuracy, or statistical power as we call it. This principle has for instance been applied in our recent study published in Frontiers in Ageing Neuroscience. Together with partners from Norway, Greece, South Korea and the US, we analysed the progression of Parkinson’s symptoms over time and were able to identify three different of disease progression types (slow, intermediate and rapidly progressing) and the corresponding disease characteristics of those three groups. Being asked to contribute to international studies like this illustrates that the Luxembourg Parkinson’s Study has put the Grand Duchy on the international map, which would never have been possible without the valuable contribution of our participants. We cannot thank them enough for their help in jointly advancing our understanding of the disease.

 

Reference: Pavelka L, Rawal R, Ghosh S, Pauly C, Pauly L, Hanff A-M, Kolber PL, Jónsdóttir SR, Mcintyre D, Azaiz K, Thiry E, Vilasboas L, Soboleva E, Giraitis M, Tsurkalenko O, Sapienza S, Diederich N, Klucken J, Glaab E, Aguayo GA, Jubal ER, Perquin M, Vaillant M, May P, Gantenbein M, Satagopam VP and Krüger R (2023) Luxembourg Parkinson’s study -comprehensive baseline analysis of Parkinson’s disease and atypical parkinsonism. Front. Neurol. 14:1330321. doi: 10.3389/fneur.2023.1330321