Clinical differences between early-onset and mid-and-late-onset Parkinson's disease: Data analysis of the Hellenic Biobank of Parkinson's disease

Background: Age at onset is one of the most critical factors contributing to the clinical heterogeneity of Par-kinson's disease (PD), and available evidence is rather conflicting.Objective: The aim of this study is to investigate the clinical differences between early-onset PD (EOPD) and mid -and-late-onset PD (MLOPD) in the Greek population, based on the existing data of the Hellenic Biobank of PD (HBPD).Methods: HBPD contains information of PD cases from two centers in Greece during 2006-2017. Patients with the A53T mutation in the SNCA gene or mutations in the GBA1 gene were excluded. Associations between clinical characteristics (motor and non-motor symptoms, side of onset, first symptom, motor complications) and MLOPD versus EOPD were explored with a single logistic regression model adjusting for gender, family history of PD, disease and dopaminergic therapy duration, disease severity (UPDRS III), levodopa equivalent daily dose, as well as each of the other clinical characteristics.Results: 675 patients (129 EOPD, 546 MLOPD) were included. EOPD was more frequently associated with dys-tonia (OR 0.19, 95% CI 0.08-0.50, p < 0.01) and motor complications (0.23, 0.07-0.76, 0.02), compared to MLOPD. Bilateral onset (9.38, 1.05-84.04, 0.045) and autonomic dysfunction (2.31, 1.04-5.11, 0.04) were more frequently associated with MLOPD.Conclusions: EOPD and MLOPD display distinct clinical profiles, regarding motor and non-motor symptoms, side of onset and motor complications in the Greek population. These differences may reflect diverse pathophysio-logical backgrounds, potentially attributed to genetic or age-related epigenetic influences.