Differential White Matter Regional Alterations in Motor Subtypes of Early Drug-Naive Parkinson's Disease Patients.

BACKGROUND: Parkinson's disease (PD) can be classified into tremor dominant (TD) and postural instability and gait difficulty (PIGD) subtypes with TD considered as the benign subtype. The neural alterations of the 2 subtypes in the early stages before administration of medications remain elusive. OBJECTIVE: This study assessed the subtype-related white matter (WM) microstructural features in newly diagnosed and drug-naive PD patients from the Parkinson's Progression Markers Initiative (PPMI). METHODS: Sixty-five early PDs with stable subtypes (52 TD and 13 PIGD patients) and 61 controls underwent diffusion tensor imaging (DTI) scanning and clinical assessment. Tract-based special statistics (TBSS), graph-theoretical and network-based analyses were used to compare WM regional and network features between groups. RESULTS: No differences in disease stages and duration were found between the 2 patient groups. TD patients showed increased fractional anisotropy (FA), but decreased radial and axial diffusivities (RD and AD) in several projection, association, and commissural tracts, compared with PIGD patients and controls. Motor severity had mild-to-moderate correlations with FA and RD of the corpus callosum (genu) in TD, but strong correlations with FA and RD of multiple association tracts in PIGD. Conversely, no significant network changes were noted. CONCLUSIONS: TD patients showed regionally increased FA but decreased diffusivities, implying neural reorganization to compensate PD pathology in early stages. PIGD patients, despite having similar disease stages and duration, exhibited more WM degradation. These results demonstrate differential WM regional features between the 2 subtypes in early PD and support the notion of TD being a benign subtype.

Structural connectome alterations in prodromal and de novo Parkinson's disease patients.

BACKGROUND: Although the clinical signs of prodromal Parkinson's disease (PD) have been identified, little is known about the neural features of the prodromal phase of PD (proPD). The aim of this study was to examine the structural network alterations from healthy aging to proPD and to early PD. METHODS: 181 non-demented and non-depressed participants comprising 55 healthy controls (HCs), 20 proPDs, and 106 de novo PD patients (dPDs) were included in the study and underwent clinical assessment and diffusion tensor imaging scanning. Graph-theoretical analysis and network-based statistics, with age and gender as nuisance covariates, were used. RESULTS: Compared with HCs and dPDs, proPD patients showed significantly elevated small-worldness and clustering coefficient (Ps < 0.01) and greater local connectivity between regions relating to motor, olfactory and sleep functions (Ps < 0.05). Although dPDs and HCs did not differ on all graph-theoretic metrics, dPD patients showed decreased connectivity within the prefrontal regions and between the left temporal and occipital lobes (P < 0.05). The connectivity strength between these regions significantly distinguished between diagnostic groups. Connectivity between bilateral SMAs was correlated with UPSIT in HCs and with UPDRS-III in dPDs. Connectivity between the right SMA and putamen was correlated RBDSQ in proPDs. CONCLUSIONS: Increased network efficiency and connectivity of proPDs and decreased local connectivity of dPDs might suggest the emergence and dissipation of neural compensation in the prodromal phase and in early PD, respectively. Nonetheless, longitudinal studies are needed to follow up the long-term structural network changes of proPD patients.

White matter microstructural characteristics in newly diagnosed Parkinson's disease: An unbiased whole-brain study.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder. Findings on specific white matter (WM) alterations in PD have been inconsistent. We hypothesized that WM changes occur in early PD patients and unbiased whole-brain analysis may provide additional evidence of pathological WM changes in PD. In this study, we examined various indexes of WM microstructure in newly diagnosed PD patients at the whole-brain level. 64 PDs with Hoehn &Yahr stage 1 (HY1PDs), 87 PDs with Hoehn &Yahr stage 2 (HYPD2s), and 60 controls (HCs) were recruited. Tract-based spatial statistics (TBSS) and diffusion connectometry were used to identify changes of WM pathways associated with PD. There were no significant differences in axial diffusivity, but HY1PDs exhibited greater fractional anisotropy (FA) and decreased mean and radial diffusivities (MD and RD) in callosal, projection, and association fibres than HCs and HY2PDs. Motor severity was inversely correlated with FA, but positively correlated with MD and RD in PD patients. Connectometry analysis also revealed increased WM density in the aforementioned tracts in PD patients, compared with HCs. Our study reveals WM enhancement, suggesting neural compensations in early PD. Longitudinal follow-up studies are warranted to identify the trajectory of WM changes alongside the progression of PD.

Neural substrates of excessive daytime sleepiness in early drug naïve Parkinson's disease: A resting state functional MRI study.

INTRODUCTION: Excessive daytime sleepiness (EDS) is a common non-motor symptom in Parkinson's disease (PD), but its neuropathology remains elusive due to the limited studies and the inclusion of medicated patients. This current study examined the neural substrates of EDS in drug naïve PD patients. METHODS: A total of 76 PD patients in the early disease stages were recruited; 16 of them had EDS, while the remaining 60 did not. Resting state functional magnetic resonance imaging (rs-fMRI) was used to determine group differences (patients with EDS vs. patients without EDS) in spontaneous neural activity indicated by regional homogeneity (ReHo). Additionally, functional connectivity (FC) of the regions showing group differences in ReHo with the entire brain was performed. RESULTS: ReHo analysis controlling for gray matter volume, age, gender, general cognition, depression, postural instability gait difficulty, and rapid eye movement sleep behavior disorder showed decreased ReHo in the left cerebellum and inferior frontal gyrus, but increased ReHo in the left paracentral lobule in PD-EDS patients, compared with patients without EDS. FC analysis controlling for the same variables as in the analysis of ReHo revealed that the three regions showing ReHo differences had decreased FC with regions in the frontal, temporal, insular and limbic lobes and cerebellum in PDs with EDS. CONCLUSION: While decreases in ReHo and FC were found, increases in ReHo were also noted, implying both neural downregulation and compensatory mechanisms in early PD patients with EDS. Longitudinal studies are warranted to clarify the long-term impact of EDS in PD.