Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease

摘要: Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous GBA are a major risk factor for Parkinson's (PD). This study examined impact on longitudinal clinical course PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 GD-associated identified 19 (8.8%) patients. In study, time to develop dementia, psychosis, wearing-off, dyskinesia examined. Survival analysis followed maximum 12-year observation (median 6.0 years), revealing that with developed dementia psychosis significantly earlier than those without (p < 0.001 p = 0.017, respectively). Adjusted hazard ratios 8.3 0.001) 3.1 0.002). No statistically significant differences observed wearing-off between groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel revealed regional cerebral blood flow was reduced bilateral parietal cortex, including precuneus mutant patients, compared matched controls mutations.