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Patients with Parkinson's disease with mild cognitive impairment (PD‐M) progress to dementia more frequently than those with normal cognition (PD‐N), but the underlying neurobiology remains unclear. This study aimed to define the specific morphological brain network alterations in PD‐M, and explore their potential diagnostic value. Twenty‐four PD‐M patients, 17 PD‐N patients, and 29 healthy controls (HC) underwent a structural MRI scan. Similarity between interregional gray matter volume distributions was used to construct individual morphological brain networks. These were analyzed using graph theory and network‐based statistics (NBS), and their relationship to neuropsychological tests was assessed. Support vector machine (SVM) was used to perform individual classification. Globally, compared with HC, PD‐M showed increased local efficiency (p =.001) in their morphological networks, while PD‐N showed decreased normalized path length (p =.008). Locally, similar nodal deficits were found in the rectus and lingual gyrus, and cerebellum of both PD groups relative to HC; additionally in PD‐M nodal deficits involved several frontal and parietal regions, correlated with cognitive scores. NBS found that similar connections were involved in the default mode and cerebellar networks of both PD groups (to a greater extent in PD‐M), while PD‐M, but not PD‐N, showed altered connections involving the frontoparietal network. Using connections identified by NBS, SVM allowed discrimination with high accuracy between PD‐N and HC (90%), PD‐M and HC (85%), and between the two PD groups (65%). These results suggest that default mode and cerebellar disruption characterizes PD, more so in PD‐M, whereas frontoparietal disruption has diagnostic potential. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. To date, among medications used to treat PD, only levodopa exhibits a limited disease-modifying effect on early-onset PD, but it cannot delay the progression of the disease. In 2018, for the first time, the World Health Organization included traditional Chinese medicine (TCM) in its influential global medical compendium. The use of TCM in the treatment of PD has a long history. At present, TCM can help treat and prevent PD. Iron metabolism is closely associated with PD. Ferroptosis, which is characterized by the accumulation of lipid peroxides, is a recently discovered form of iron-dependent cell death. The research literature indicates that ferroptosis in dopaminergic neurons is an important pathogenetic mechanism of PD. TCM may thus play unique roles in the treatment of PD and provide new ideas for the treatment of PD by regulating pathways associated with ferroptosis. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI), a well‐defined nonmotor manifestation of Parkinson's disease (PD), greatly impairs functioning and quality of life. However, the contribution of cerebral perfusion, quantified by arterial spin labeling (ASL), to MCI in PD remains poorly understood. The selection of an optimal delay time is difficult for single‐delay ASL, a problem which is avoided by multidelay ASL. This study uses a multidelay multiparametric ASL to investigate cerebral perfusion including cerebral blood flow (CBF) and arterial transit time (ATT) in early stage PD patients exhibiting MCI using a voxel‐based brain analysis. Magnetic resonance imaging data were acquired on a 3.0 T system at rest in 39 early stage PD patients either with MCI (PD‐MCI, N = 22) or with normal cognition (PD‐N, N = 17), and 36 age‐ and gender‐matched healthy controls (HCs). CBF and ATT were compared among the three groups with SPM using analysis of variance followed by post hoc analyses to define regional differences and examine their relationship to clinical data. PD‐MCI showed prolonged ATT in right thalamus compared to both PD‐N and HC, and in right supramarginal gyrus compared to HC. PD‐N showed shorter ATT in left superior frontal cortex compared to HC. Prolonged ATT in right thalamus was negatively correlated with the category fluency test (p = .027, r = −0.495) in the PD‐MCI group. This study shows that ATT may be a more sensitive marker than CBF for the MCI, and highlights the potential role of thalamus and inferior parietal region for MCI in early stage PD. [ABSTRACT FROM AUTHOR]

The association between glucocerebrosidase (GBA) mutations and Parkinson's disease (PD) is attracting increased attention worldwide. Results from previous studies on the association of GBA mutations with PD in different ethnicities remain contradictory. In order to derive a more comprehensive understanding of the relationship between the most common GBA mutations, L444P and N370S and PD susceptibility, an updated meta-analysis was performed by searching PUBMED, EMBASE, MEDLINE, and EBSCO databases. Twenty five studies including 9, 599 cases and 13, 541 controls were collected in the end. The summary of odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated using fixed- and random-effects models, when appropriate. Overall, our meta-analysis provided evidence that both were risk factors associated with increased PD susceptibility. When stratified by ethnicities, the associations varied among different ethnical origins. [ABSTRACT FROM AUTHOR]

• Patients with FOG exhibited a disrupted topological organization of functional brain networks. • Nodal centralities and functional connectivity increased in widely distributed networks in PD patients with FOG. • The altered nodal centralities in the right hippocampus were positively correlated with FOG severity. Freezing of gait (FOG) is a common and debilitating gait disturbance in patients with Parkinson's disease (PD), but the potential mechanisms are still unclear. This study aimed to explore alterations in the topological organization of whole-brain functional networks in PD patients with FOG. We recruited 75 patients with PD, 37 patients with FOG and 38 patients without FOG, to undergo resting-state functional magnetic resonance imaging (fMRI). The whole-brain functional networks were constructed, and the topological properties at three (global, nodal, and connectional) levels were analyzed using graph theory approaches. Compared with patients without FOG, patients with FOG exhibited altered global topological properties (a significant decrease in the normalized clustering coefficient and small-worldness), implying a shift toward randomization in their functional brain networks. At the node and connectional levels, patients with FOG showed increased nodal centralities and functional connectivity in the sensorimotor network, frontoparietal network, visual network, subcortical and limbic regions, and decreased nodal centralities in the frontoparietal network and the cerebellum. Furthermore, the altered nodal centralities in the right hippocampus (HIP) were positively correlated with FOG severity. This study suggests that FOG in PD is associated with disrupted topological organization of whole-brain functional networks, involving dysfunction of the multiple networks. [ABSTRACT FROM AUTHOR]

Although early-onset Parkinson's disease (EOPD) has a more penetrant genetic etiology, the genetic architecture of EOPD remains unclear. The objectives of this study were to assess the genetic and clinical features of EOPD among ethnic Chinese from mainland China. Using whole-exome sequencing, we performed genetic analyses of 240 participants including 193 with sporadic and 47 with familial EOPD (age of onset <50 years). In total, 18 patients (7.5%) harbored pathogenic or likely pathogenic variants in known PD genes. Among these variants, biallelic variants in Parkin and PINK1 were responsible for 4.2% of cases, and rare likely pathogenic variants in LRRK2 (1.7%) also appeared to be a relatively common cause of EOPD. Notably, 7.5% of patients carried risk variants in either LRRK2 or GBA , which should also be considered for EOPD. Nevertheless, 41 patients (17.1%) had rare variants of unknown significance. In conclusion, our findings provide a better understanding of the genetic architecture of PD among ethnic Chinese, and the pathogenicity of numerous rare variants should be further investigated. • 18 patients (7.5%) carried pathogenic or likely pathogenic variants in known PD genes. • (Likely) pathogenic variants in Parkin and PINK1 were responsible for 4.2% of the patients. • Rare likely pathogenic variants in LRRK2 (1.7%) also appeared to be a relatively common cause of EOPD. • 7.5% of patients carried risk variants in either LRRK2 or GBA. [ABSTRACT FROM AUTHOR]