Patients with Parkinson's disease (PD) were often observed with gastrointestinal symptoms, which preceded the onset of motor symptoms. Neuropathology of PD has also been found in the enteric nervous system (ENS). Many studies have reported significant PD-related alterations of gut microbiota. This meta-analysis was performed to evaluate the differences of gut microbiota between patients with PD and healthy controls (HCs) across different geographical regions. We conducted a systematic online search for case-control studies detecting gut microbiota in patients with PD and HCs. Mean difference (MD) and 95% confidence interval (CI) were calculated to access alterations in the abundance of certain microbiota families in PD. Fifteen case-control studies were included in this meta-analysis study. Our results showed significant lower abundance levels of Prevotellaceae (MD = −0.37, 95% CI = −0.62 to −0.11), Faecalibacterium (MD = −0.41, 95% CI: −0.57 to −0.24), and Lachnospiraceae (MD = −0.34, 95% CI = −0.59 to −0.09) in patients with PD compared to HCs. Significant higher abundance level of Bifidobacteriaceae (MD = 0.38, 95%; CI = 0.12 to 0.63), Ruminococcaceae (MD = 0.58, 95% CI = 0.07 to 1.10), Verrucomicrobiaceae (MD = 0.45, 95% CI = 0.21 to 0.69), and Christensenellaceae (MD = 0.20, 95% CI = 0.07 to 0.34) was also found in patients with PD. Thus, shared alterations of certain gut microbiota were detected in patients with PD across different geographical regions. These PD-related gut microbiota dysbiosis might lead to the impairment of short-chain fatty acids (SCFAs) producing process, lipid metabolism, immunoregulatory function, and intestinal permeability, which contribute to the pathogenesis of PD.

Perivascular space (PVS) is associated with neurodegenerative diseases, while its effect on Parkinson’s disease (PD) remains unclear. We aimed to investigate the clinical and neuroimaging significance of PVS in basal ganglia (BG) and midbrain in early-stage PD. We recruited 40 early-stage PD patients and 41 healthy controls (HCs). Both PVS number and volume were calculated to evaluate PVS burden on 7 T magnetic resonance imaging images. We compared PVS burden between PD and HC, and conducted partial correlation analysis between PVS burden and clinical and imaging features. PD patients had a significantly more serious PVS burden in BG and midbrain, and the PVS number in BG was significantly correlated to the PD disease severity and L-dopa equivalent dosage. The fractional anisotropy and mean diffusivity values of certain subcortical nuclei and white matter fibers within or nearby the BG and midbrain were significantly correlated with the ipsilateral PVS burden indexes. Regarding to the midbrain, the difference between bilateral PVS burden was, respectively, correlated to the difference between fiber counts of white fiber tract passing through bilateral substantia nigra in PD. Our study suggests that PVS burden indexes in BG are candidate biomarkers to evaluate PD motor symptom severity and aid in predicting medication dosage. And our findings also highlight the potential correlations between PVS burden and both grey and white matter microstructures.

The brain glymphatic system is involved in the clearance of misfolding α-synuclein, the impaired glymphatic system may contribute to the progression of Parkinson’s disease (PD). We aimed to analyze the diffusion tensor image along the perivascular space (DTI-ALPS) and perivascular space (PVS) burden to reveal the relationship between the glymphatic system and PD. A cross-sectional study using a 7 T MRI of 76 PD patients and 48 controls was performed to evaluate the brain’s glymphatic system. The DTI-ALPS and PVS burden in basal ganglia were calculated. Correlation analyses were conducted between DTI-ALPS, PVS burden and clinical features. We detected lower DTI-ALPS in the PD subgroup relative to controls, and the differences were more pronounced in patients with Hoehn & Yahr stage greater than two. The decreased DTI-ALPS was only evident in the left hemisphere in patients in the early stage but involved both hemispheres in more advanced PD patients. Decreased DTI-ALPS were also correlated with longer disease duration, higher Unified Parkinson’s Disease Rating Scale motor score (UPDRS III) and UPDRS total scores, as well as higher levodopa equivalent daily dose. Moreover, the decreased DTI-ALPS correlated with increased PVS burden, and both indexes correlated with PD disease severity. This study demonstrated decreased DTI-ALPS in PD, which might initiate from the left hemisphere and progressively involve right hemisphere with the disease progression. Decreased DTI-ALPS index correlated with increased PVS burden, indicating that both metrics could provide supporting evidence of an impaired glymphatic system. MRI evaluation of the PVS burden and diffusion along PVS are potential imaging biomarkers for PD for disease progression.

Heterogeneity between late-onset Parkinson's disease (LOPD) and early-onset Parkinson's disease (EOPD) is mainly reflected in the following aspects including genetics, disease progression, drug response, clinical manifestation, and neuropathological change. Although many studies have investigated these differences in relation to clinical significance, the functional processing circuits and underlying neural mechanisms have not been entirely understood. In this study, regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) maps were used to explore different spontaneous brain activity patterns in EOPD and LOPD patients. Abnormal synchronizations were found in the motor and emotional circuits of the EOPD group, as well as in the motor, emotional, and visual circuits of the LOPD group. EOPD patients showed functional activity change in the visual, emotional and motor circuits, and LOPD patients only showed increased functional activity in the emotional circuits. In summary, the desynchronization process in the LOPD group was relatively strengthened, and the brain areas with changed functional activity in the EOPD group were relatively widespread. The results might point out different impairments in the synchronization and functional activity for EOPD and LOPD patients.

Changes in basal ganglia (BG) perivascular spaces (PVSs) are related to motor and cognitive behaviors in Parkinson’s disease (PD). However, the correlation between the initial motor phenotype and PVSs distribution/burden in PD freezing of gait (FOG) remains unclear. In addition, the normal-sized PVSs (nPVSs) have not been well-studied. With high-resolution 7T-MRI, we studied nPVSs burden in BG, thalamus, midbrain and centrum semiovale. The numbers and volume of nPVSs were assessed in 10 healthy controls, 10 PD patients without FOG, 20 with FOG [10 tremor dominant (TD), 10 non-TD subtype]. Correlation analyses were further performed in relation to clinical parameters. In this proof of concept study, we found that the nPVS burden of bilateral and right BG were significantly higher in freezers. A negative correlation existed between the tremor score and BG-nPVSs count. A positive correlation existed between the levodopa equivalent daily dose and BG-nPVSs count. The nPVS burden correlated with the progression to FOG in PD, but the distribution and burden of nPVS differ in TD vs. non-TD subtypes. High resolution 7T-MRI is a sensitive and reliable tool to evaluate BG-nPVS, and may be a useful imaging marker for predicting gait impairment that may evolve into FOG in PD.

No abstract

No abstract