Repetitive transcranial magnetic stimulation (rTMS) fails to improve cognition in patients with parkinson's disease: a Meta-analysis of randomized controlled trials.

BACKGROUND: Cognitive decline is one of the greatest concerns for patients with Parkinson's disease (PD) and their care partners. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological treatment option used to improve cognitive function in PD, but its efficacy is unclear. We performed a meta-analysis to determine whether rTMS improves cognition in PD patients. METHODS: Eligibility criteria (PICOS) were as follows: (1) 'P': The patients participating were diagnosed with idiopathic PD; (2) 'I': Intervention using rTMS; (3) 'C': Sham stimulation as control; (4) 'O': The outcome of the study included cognitive evaluations; (5) 'S': The study adopted randomized controlled design. The standardized mean difference (SMD) of change of score was applied to measure efficacy, and we used Version 2 of the Cochrane tool to assess risk of bias. RESULTS: Twelve studies met the inclusion criteria. Compared with sham-controlled group, the pooled result showed a non-significant short-term effect of rTMS on global cognition (SMD: -0.15, 95% CI: -0.59 to 0.29, I2 = 36.7%), executive function (SMD: 0.03, 95% CI: -0.21 to 0.26, I2 = 0.0%), and attention and working memory (SMD: 0.05, 95% CI: -0.25 to 0.35, I2 = 0.0%). Long-term outcomes were either shown to be statistically nonsignificant. CONCLUSIONS: Based on a limited number of studies, rTMS fails to improve cognition in PD. We call for additional high-quality randomized controlled trials with adequate sample sizes to determine the efficacy of rTMS.

Idebenone-Activating Autophagic Degradation of α-Synuclein via Inhibition of AKT-mTOR Pathway in a SH-SY5Y-A53T Model of Parkinson's Disease: A Network Pharmacological Approach.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, which currently lacks disease-modifying therapy to slow down its progression. Idebenone, a coenzyme Q10 (CQ10) analogue, is a well-known antioxidant and has been used to treat neurological disorders. However, the mechanism of Idebenone on PD has not been fully elucidated. This study aims to predict the potential targets of Idebenone and explore its therapeutic mechanism against PD. METHOD: We obtained potential therapeutic targets through database prediction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Next, we constructed and analyzed a protein-protein interaction network (PPI) and a drug-target-pathway-disease network. A molecular docking test was conducted to identify the interactions between Idebenone and potential targets. Lastly, a PD cell line of SH-SY5Y overexpressing mutant α-synuclein was used to validate the molecular mechanism. RESULT: A total of 87 targets were identified based on network pharmacology. The enrichment analysis highlighted manipulation of MAP kinase activity and the PI3K-AKT signaling pathway as potential pharmacological targets for Idebenone against PD. Additionally, molecular docking showed that AKT and MAPK could bind tightly with Idebenone. In the cell model of PD, Idebenone activated autophagy and promoted α-synuclein degradation by suppressing the AKT/mTOR pathway. Pretreating cells with chloroquine (CQ) to block autophagic flux could diminish the pharmacological effect of Idebenone to clear α-synuclein. CONCLUSION: This study demonstrated that Idebenone exerts its anti-PD effects by enhancing autophagy and clearance of α-synuclein, thus providing a theoretical and experimental basis for Idebenone therapy against PD.

RIT2 polymorphism is associated with Parkinson's disease in a Han Chinese population.

Recently, a meta-analysis including 5 large genome-wide association studies has identified rs12456492 variant of RIT2 gene as a novel risk locus for Parkinson's disease (PD) in Caucasian populations. However, the association between RIT2 polymorphism and PD risk has not been positively replicated in Asian population yet. We detected the genotypes of rs12456492 in 524 PD patients and 521 control subjects from a Han Chinese population. The allele and genotype distribution of rs12456492 variant were significantly different between PD patients and controls (allele p = 0.001, genotype p = 0.002). Logistic regression analysis showed that the G-carrying genotype (AG + GG) individuals exhibited a nearly 1.4-fold increased risk for PD compared with the AA genotype carriers (OR = 1.390; 95% confidence interval = 1.079-1.791; p = 0.011). Our data support that the carriage of G allele of rs12456492 variant of RIT2 gene significantly increases the risk for PD in Han Chinese population, suggesting a potential role of RIT2 in the etiology of PD.

[Correlation of collateral circulation and prognosis in patients with acute cerebral infarction].

OBJECTIVE: To evaluate the correlation of collateral circulation with prognosis in patients with acute cerebral infarction. METHODS: A total of 260 patients with acute ischemic stroke within 1 week of symptom onset underwent digital subtraction angiogram (DSA). The National Institutes of Health Stroke Scale (NIHSS) scores were obtained at admission. And the Modified Rankin scores (mRS) were assessed at a 3-month follow-up. The follow-up data were acquired through clinic visits or telephone interviews. RESULTS: Among them, 86 were found to have intra- or extra-cranial culprit artery severe stenosis or occlusion. And 36 (75.00%) in 48 patients had collateral arterial circulation while 11 (28.64%) in 38 patients posterior circulation. There were statistical differences in the NIHSS scores at admission and favorite clinical outcome (mRS ≤ 2) at 3-month follow-up for patients with and without collateral circulation. CONCLUSION: DSA is the golden standard for the assessment of collateral circulation in patients with severe cerebral artery stenosis or occlusion. The prognosis is better in stroke patients with collateral circulation.