Disease Progression in Patients with Parkin‐Related Parkinson's Disease in a Longitudinal Cohort

ABSTRACT Background There was a paucity of follow‐up studies in the disease progression of early‐onset PD patients with Parkin mutations (Parkin‐EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin‐EOPD patients. Methods Genetic analysis was performed via target sequencing and multiplex ligation‐dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow‐up revisions were investigated as the Parkin‐EOPD group. Fifty‐two patients with at least 2 follow‐up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU‐EOPD) group. A linear mixed‐effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition. Results At baseline, the Parkin‐EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS‐III) (off‐medication) than the GU‐EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS‐III score (off‐medication) was lower in the Parkin‐EOPD group (0.203 [0.3162] points per year) than in the GU‐EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS‐III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin‐EOPD group showed better maintenance of spatial processing ability compared with the GU‐EOPD group (P = 0.027). Conclusion Parkin‐EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU‐EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society