Background Reduced arm swing is a well-known clinical feature of Parkinson’s disease (PD), often observed early in the course of the disease. We hypothesized that subtle changes in arm swing and axial rotation may also be detectable in the prodromal phase. Objective The purpose of this study was to evaluate the relationship between the LRRK2-G2019S mutation, arm swing, and axial rotation in healthy nonmanifesting carriers and noncarriers of the G2019S mutation and in patients with PD. Methods A total of 380 participants (186 healthy nonmanifesting controls and 194 PD patients) from 6 clinical sites underwent gait analysis while wearing synchronized 3-axis body-fixed sensors on the lower back and bilateral wrists. Participants walked for 1 minute under the following 2 conditions: (1) usual walking and (2) dual-task walking. Arm swing amplitudes, asymmetry, variability, and smoothness were calculated for both arms along with measures of axial rotation. Results A total of 122 nonmanifesting participants and 67 PD patients were carriers of the G2019S mutation. Nonmanifesting mutation carriers walked with greater arm swing asymmetry and variability and lower axial rotation smoothness under the dual task condition when compared with noncarriers (P < .04). In the nonmanifesting mutation carriers, arm swing asymmetry was associated with gait variability under dual task (P = .003). PD carriers showed greater asymmetry and variability of movement than PD noncarriers, even after controlling for disease severity (P < .009). Conclusions The G2019S mutation is associated with increased asymmetry and variability among nonmanifesting participants and patients with PD. Prospective studies should determine if arm swing asymmetry and axial rotation smoothness may be used as motor markers of prodromal PD.

Mutations in GBA1 are a well-established risk factor for Parkinson disease (PD). GBA-associated PD (GBA-PD) may have a higher burden of nonmotor symptoms than idiopathic PD (IPD). We sought to characterize the relationship between GBA-PD and neuropsychiatric symptoms. Subjects were screened for common GBA1 mutations. GBA-PD (n=31) and non-carrier (IPD; n=55) scores were compared on the Unified Parkinson Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Beck Depression Inventory (BDI), and the State-Trait Anxiety Index (STAI). In univariate comparisons, GBA-PD had a greater prevalence of depression (33.3%) versus IPD (13.2%) (p<0.05). In regression models controlling for age, sex, disease duration, motor disability, and MoCA score, GBA-PD had an increased odds of depression (OR 3.66, 95% CI 1.13–11.8) (p=0.03). Post-hoc analysis stratified by sex showed that, among men, GBA-PD had a higher burden of trait anxiety and depression than IPD; this finding was sustained in multivariate models. Among women, GBA-PD did not confer greater psychiatric morbidity than IPD. These results suggest that GBA1 mutations confer greater risk of neuropsychiatric morbidity in PD, and that sex may affect this association.

Background Rapid eye movement sleep Behavior Disorder occurs with idiopathic Parkinson disease (PD), and often precedes PD. Its frequency in LRRK2-PD and utility as a pre-clinical marker has not been established. Methods 144 idiopathic PD, 142 LRRK2 G2019S mutation PD, 117 non-manifesting carriers, 93 related non-carriers, and 40 controls completed the Rapid eye movement sleep Behavior Disorder Screening Questionnaire. Results 30.6% idiopathic PD, 19.7% LRRK2-PD, 6% non-manifesting carriers, 20.4% related non-carriers, and 15% controls met cut-scores. The likelihood of abnormal scores was decreased in LRRK2-PD vs. idiopathic PD (OR=0.55, p=0.03), non-manifesting carriers vs. related non-carriers (OR=0.25, p<0.01), and PD <3 years duration, 1/19 LRRK2-PD vs. 14/41 idiopathic PD (p<0.05). Conclusions There is a lower frequency of abnormal Questionnaire scores in LRRK2-PD, especially in early LRRK2-PD, and in non-manifesting carriers. Therefore, the Rapid eye movement sleep Behavior Disorder Questionnaire is unlikely to serve as a pre-clinical marker for phenoconversion to PD.