title: Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease.
abstract: Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival time analysis followed a maximum 12-year observation (median 6.0 years), revealing that PD patients with GD-associated mutations developed dementia and psychosis significantly earlier than those without mutations (p < 0.001 and p = 0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically significant differences were observed for wearing-off and dyskinesia between the groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in the bilateral parietal cortex, including the precuneus of GD-associated mutant PD patients, compared with matched PD controls without mutations.
authors.affiliation: Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Oeda
authors.affiliation: Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Umemura
authors.affiliation: Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tomita
authors.affiliation: Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohsaka
authors.affiliation: Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan.
authors.forename: Kwiyoung
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Neurology, Toneyama National Hospital, Osaka, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Neurology, Toneyama National Hospital, Osaka, Japan.
authors.forename: Harutoshi
authors.initials: H
authors.lastname: Fujimura
authors.affiliation: Department of Neurology, Minami-Kyoto National Hospital, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan. Electronic address: sawada@unh.hosp.go.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sawada
mesh_terms: D000368:Aged; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068079:Motor Disorders / Q000209:etiology* / Q000235:genetics*; D009154:Mutation; D010296:Parietal Lobe / Q000098:blood supply; D010300:Parkinson Disease / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D012039:Regional Blood Flow; D012189:Retrospective Studies; D012307:Risk Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D005962:Glucosylceramidase
keywords: Clinical course; Glucocerebrosidase gene; MIBG scintigraphy; Parkinson's disease; Risk factor; SPECT