Comprehensive analysis of clinical and biological features in Parkinson's disease associated with the LRRK2 G2019S mutation: Data from the PPMI study

Abstract

The Parkinson's Progression Marker Initiative (PPMI) aims to identify biomarkers for Parkinson's disease (PD) risk, onset, and progression. This study focuses on the G2019S missense mutation in the LRRK2 gene, which is associated with hereditary and sporadic PD. Utilizing data from the PPMI database, we conducted an analysis of baseline clinical characteristics, as well as serum and cerebrospinal fluid levels in two groups: patients with PD with the G2019S mutation (PD + G2019S) and patients with PD without the mutation (PD-G2019S). Multiple linear regression and longitudinal analysis were performed, controlling for confounding factors. Compared to the PD-G2019S group, the PD + G2019S group showed more obvious initial motor dysfunction-higher baseline Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) scores (false discovery rate [FDR]-adjusted p < 0.001), but progressed more slowly. Mechanism of Coordinated Access and activities of daily living (ADL) scores were lower at baseline (FDR-adjusted p < 0.001), whereas Scales for Outcomes of Parkinson's Disease (SCOPA)-Thermoregulatory (FDR-adjusted p = 0.015) scores were higher, emphasizing the increase of non-motor symptoms associated with LRRK2-G2019S mutation. During the follow-up period, the motor and non-motor symptoms changed dynamically with time, and there were longitudinal differences in the scores of MDS-UPDRS (FDR-adjusted P_I = 0.013, P_II = 0.008, P_IV < 0.001), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (FDR-adjusted p = 0.027), SCOPA-Thermoregulatory (FDR-adjusted p = 0.021), and ADL (FDR-adjusted p = 0.027) scale scores. PD associated with the LRRK2 G2019S mutation demonstrated more severe symptoms at baseline but slower progression. Motor complications and thermoregulatory disorders were more pronounced.