Comparing the effects of GBA variants and onset age on clinical features and progression in Parkinson's disease.

OBJECTIVE: Glucosylceramidase (GBA) variants and onset age significantly affect clinical phenotype and progression in Parkinson's disease (PD). The current study compared clinical characteristics at baseline and cognitive and motor progression over time among patients having GBA-related PD (GBA-PD), early-onset idiopathic PD (early-iPD), and late-onset idiopathic PD (late-iPD). METHODS: We recruited 88 GBA-PD, 167 early-iPD, and 488 late-iPD patients in this study. A subset of 50 GBA-PD, 81 early-iPD, and 223 late-iPD patients was followed up at least once, with a 3.0-year mean follow-up time. Linear mixed-effects models helped evaluate the rate of change in the Unified Parkinson's Disease Rating Scale motor and Montreal Cognitive Assessment scores. RESULTS: At baseline, the GBA-PD group showed more severe motor deficits and non-motor symptoms (NMSs) than the early-iPD group and more NMSs than the late-iPD group. Moreover, the GBA-PD group had more significant cognitive and motor progression, particularly bradykinesia and axial impairment, than the early-iPD and late-iPD groups at follow-up. However, the early-onset GBA-PD (early-GBA-PD) group was similar to the late-onset GBA-PD (late-GBA-PD) group in baseline clinical features and cognitive and motor progression. CONCLUSION: GBA-PD patients exhibited faster cognitive and motor deterioration than early-iPD and late-iPD patients. Thus, subtype classification based on genetic characteristics rather than age at onset could enhance the prediction of PD disease progression.

Structural and functional changes in the default mode network in drug-resistant epilepsy.

PURPOSE: To investigate brain network properties and connectivity abnormalities of the default mode network (DMN) in drug-resistant epilepsy (DRE). The study was based on probabilistic fiber tracking and functional connectivity (FC) analysis, to explore the structural and functional connectivity patterns change between frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). METHODS: A total of 33 DRE patients (18 TLE and 15 FLE) and 30 healthy controls (HCs) were recruited. The volume fraction of the septal brain region of the DMN in DRE was calculated using FreeSurfer. The FC analysis was performed using Data Processing and Analysis for Brain Imaging in MATLAB. The structural connections between brain regions of the DMN were calculated based on probabilistic fiber tracking. RESULTS: The left precuneus (PCUN) volumes in epilepsy groups were lower than that in HCs. Compared with FLE, TLE showed reduced FC between the left hippocampus (HIP) and PCUN/medial frontal gyrus, and between the right inferior parietal lobule (IPL) and right superior temporal gyrus. Compared with HCs, FLE showed increased FCs between the right IPL and occipital lobe, and between the left superior frontal gyrus (SFG) and bilateral superior temporal gyrus. In terms of structural connectivity, TLE exhibited increased connectivity strength between the left SFG and left PCUN, and showed reduced connection strength between the left HIP and left posterior cingulate gyrus/left PCUN, when compared with the FLE. CONCLUSIONS: TLE and FLE patients showed structural and functional changes in the DMN. Compared with FLE patients, the TLE patients showed reduced structural and functional connection strengths between the left HIP and PCUN. These alterations in connection strengths holds promise for the identification of TLE and FLE.

Structural and functional differences of the thalamus between drug-naïve Parkinson's disease motor subtypes.

Objective: The thalamus is an integrative hub of motor circuits in Parkinson's disease (PD). This study aimed to investigate the alterations of structure and functional connectivity (FC) of the thalamic subregions in the tremor-dominant (TD) subtype and the postural instability and gait difficulty (PIGD) subtype in PD. Methods: A total of 59 drug-naïve patients (24 TD and 35 PIGD) and 37 healthy controls were recruited. The volumes of the thalamus and the thalamic subregions were calculated using FreeSurfer. Functional connectivity (FC) analysis of the resting-state functional MRI (rsfMRI) was conducted on the thalamic subregions. Finally, the altered structure and FC were used for correlation analysis with clinical motor scores and for further motor subtypes differentiation. Results: The volumes of the left posterior parietal thalamus (PPtha) in TD patients were significantly lower than those of PIGD patients. Compared with PIGD patients, TD patients exhibited higher FC between the thalamic subregions, the left middle temporal gyrus (MTG), the right dorsolateral superior frontal gyrus (SFGdl), the left middle occipital gyrus (MOG), and the right superior temporal gyrus (STG). Compared with HCs, TD patients showed higher FC between the thalamic subregions and the right SFGdl, as well as the left MOG. Compared with HCs, PIGD patients showed lower FC between the thalamic subregions and the left MTG. In addition, the altered FC was closely related to clinical symptoms and performed high-discriminative power in differentiating the motor subtypes. Conclusion: Increased FC between the thalamic subregions and the sensory cortices in TD patients may indicate a better compensatory capacity for impairment of sensory information integration than that in PIGD patients. The altered FC between the thalamus and the MTG was a potential biomarker for the distinction of the PD motor subtypes.