The motor phenotype of Parkinson's disease in relation to age at onset
Wickremaratchi MM., Knipe MDW., Sastry BSD., Morgan E., Jones A., Salmon R., Weiser R., Moran M., Davies D., Ebenezer L., Raha S., Robertson NP., Butler CC., Ben-Shlomo Y., Morris HR.
Background: Parkinson's disease (PD) is heterogeneous and age at onset may define variation in clinical phenotype. Most previous studies have used various age cut-offs and have been based on clinical case series. Methods: We have studied the association between clinical features and age of onset in 358 community-based and regional patients with PD. Results: Tremor at presentation is twice as common in those with onset over 64 years as compared to those with onset under 45 (early onset PD - EOPD) and becomes more common with increasing age at onset (p values for trend ≤ 0.004). Dystonia affects 60% of those with EOPD, shows a curvilinear relationship with age at onset (cubic versus linear p=0.01) with highest risk in patients whose disease began before 48 years. In this study age at onset was a strong predictor of the development of dyskinesias, with younger age associated with a higher risk of dyskinesias. Following multivariable analysis, allowing for possibly confounding factors (disease duration, L-DOPA dosage, L-DOPA treatment duration) younger age at onset, (less than 55 years) predicted the development of L-DOPA induced dyskinesia (odds ratio <45 years 2.1, 95% CI 1.0, 4.8; odds ratio < 55 years 3.8, 95% CI 1.8, 8.0). Only 2/70 (2.9%) EOPD patients carried pathogenic parkin or PINK1 mutations and the clinical differences between early and late onset disease were not explained by the presence of mutations in these genes. Discussion: This study highlights the clinical differences between early and late onset PD, which have important implications for diagnosis and management. © 2011 Movement Disorder Society.