Luxembourg Parkinson's study -comprehensive baseline analysis of Parkinson's disease and atypical parkinsonism

Abstract

Background: Deep phenotyping of Parkinson's disease (PD) is essential to investigate this fastest-growing neurodegenerative disorder. Since 2015, over 800 individuals with PD and atypical parkinsonism along with more than 800 control subjects have been recruited in the frame of the observational, monocentric, nation-wide, longitudinal-prospective Luxembourg Parkinson's study.

Objective: To profile the baseline dataset and to explore risk factors, comorbidities and clinical profiles associated with PD, atypical parkinsonism and controls.

Methods: Epidemiological and clinical characteristics of all 1,648 participants divided in disease and control groups were investigated. Then, a cross-sectional group comparison was performed between the three largest groups: PD, progressive supranuclear palsy (PSP) and controls. Subsequently, multiple linear and logistic regression models were fitted adjusting for confounders.

Results: The mean (SD) age at onset (AAO) of PD was 62.3 (11.8) years with 15% early onset (AAO < 50 years), mean disease duration 4.90 (5.16) years, male sex 66.5% and mean MDS-UPDRS III 35.2 (16.3). For PSP, the respective values were: 67.6 (8.2) years, all PSP with AAO > 50 years, 2.80 (2.62) years, 62.7% and 53.3 (19.5). The highest frequency of hyposmia was detected in PD followed by PSP and controls (72.9%; 53.2%; 14.7%), challenging the use of hyposmia as discriminating feature in PD vs. PSP. Alcohol abstinence was significantly higher in PD than controls (17.6 vs. 12.9%, p = 0.003).

Conclusion: Luxembourg Parkinson's study constitutes a valuable resource to strengthen the understanding of complex traits in the aforementioned neurodegenerative disorders. It corroborated several previously observed clinical profiles, and provided insight on frequency of hyposmia in PSP and dietary habits, such as alcohol abstinence in PD.Clinical trial registration: clinicaltrials.gov, NCT05266872.

Keywords: Parkinson’s disease; REM-sleep behaviour disorder; environment exposure; hyposmia; parkinsonian disorders; progressive supranuclear palsy.

Figure 1

Recruitment flowchart and analytical steps of the Luxembourg Parkinson’s study baseline dataset. Parkinson’s disease (PD); progressive supranuclear palsy (PSP); parkinsonism (PS), vascular parkinsonism (VaP); dementia with Lewy Bodies (DLB); multiple system atrophy (MSA); spinocerebellar ataxia (SCA).

Figure 2

Distribution of diagnostic groups with parkinsonism (PS) in the baseline dataset of Luxembourg Parkinson’s study. The annotations correspond to diagnostic group, number of individuals (n) and the proportion (%) to the overall individuals with PS in the baseline dataset. Parkinson’s disease (PD); progressive supranuclear palsy (PSP; including corticobasal syndrome under PSP based on MDS diagnostic criteria from 2017); dementia with Lewy Bodies (DLB); multiple system atrophy (MSA); rare PS includes one case of rapid-onset dystonia-parkinsonism with DYT12 mutation, one case of chronic progressive external ophthalmoplegia (CPEO) and one case of frontotemporal dementia with PS.

Figure 3

Forest plot with results of multiple regression model including Parkinson’s disease individuals (PD) vs. controls adjusted for age at assessment, sex and total languages spoken. The estimates correspond to the regression coefficient with 95% confidence intervals (95% CI). Significant associations after Bonferroni correction for multiple testing were annotated by an asterisk where red colour indicates positive significant association and blue colour negative significant association, respectively, between PD vs. controls and the clinical variable.

Figure 4

Forest plot with results of multiple regression model including Parkinson’s disease individuals (PD) vs. progressive supranuclear palsy (PSP) adjusted for age at assessment, sex, disease duration and total languages spoken. Estimate corresponds to the regression coefficient with confidence interval 95% (CI). Significant associations after Bonferroni correction for multiple testing were annotated by an asterisk where red colour indicates positive significant association and blue colour negative significant association, respectively, between PD vs. PSP and the clinical variable.

Figure 5

Forest plot with results of multiple regression model including vs. progressive supranuclear palsy (PSP) vs. controls adjusted for age at assessment, sex and total languages spoken. Estimate corresponds to the regression coefficient with confidence interval 95% (CI). Significant associations after Bonferroni correction for multiple testing were annotated by an asterisk where red colour indicates positive significant association and blue colour negative significant association, respectively, between PSP vs. controls and the clinical variable.