Low serum uric acid levels may be a potential biomarker of poor sleep quality in patients with Parkinson's disease.

BACKGROUND: Sleep disorders are common non-motor symptoms in patients with Parkinson's disease (PD). However, the pathogenesis of sleep disorders in PD patients remains unclear. Previous studies have implicated oxidative stress in sleep disorders associated with PD. Considering uric acid (UA) acts as a natural antioxidant, in this study, we aimed to assess the use of serum UA as a potential biomarker of sleep disorder in PD patients. METHODS: This study recruited 149 PD patients and 84 Age- and sex-matched individuals. According to the Pittsburgh Sleep Quality Index (PSQI) score, PD patients were divided into three groups, good (≤5), intermediate (6-10), and poor (>10). Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were also performed to identify clinical features and serum UA levels that help establish an accurate diagnostic model for poor sleep quality in PD patients. RESULTS: PD patients who experienced poor sleep quality had lower serum UA levels. PSQI scores have significant negative relationships with serum UA levels and significant positive relationships with Hamilton Depression Scale (HAMD) scores in PD. Poor sleep quality was independently associated with serum UA levels and HAMD scores. A serum UA level of 328.7 µmol/L and HAMD scores of 19.5 could distinguish PD patients with poor or intermediate sleep to a certain extent, sensitivity of 79.4% and specificity of 76.6%. CONCLUSIONS: Low serum UA levels may correlate with the severity of sleep disorder in PD patients and may serve as a biomarker for poor sleep quality in PD.

Abnormal cortical atrophy and functional connectivity are associated with depression in Parkinson's disease.

Objective: This study aimed to investigate the association of altered cortical thickness and functional connectivity (FC) with depression in Parkinson's disease (PD). Materials and methods: A total of 26 non-depressed PD patients (PD-ND), 30 PD patients with minor depression (PD-MnD), 32 PD patients with major depression (PD-MDD), and 30 healthy controls (HC) were enrolled. Differences in cortical thickness among the four groups were assessed, and the results were used to analyze FC differences in regions of cortical atrophy. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were also performed to identify clinical features and neuroimaging biomarkers that might help in the prediction of PD-MDD. Results: Patients with PD-MDD showed decreased cortical thickness compared to patients with PD-ND in the left superior temporal and right rostral middle frontal gyri (RMFG), as well as weak FC between the left superior temporal gyrus and right cerebellum posterior lobe and between right RMFG and right inferior frontal gyrus and insula. The combination of cortical thickness, FC, and basic clinical features showed strong potential for predicting PD-MDD based on the area under the ROC curve (0.927, 95% CI 0.854-0.999, p < 0.001). Conclusion: Patients with PD-MDD show extensive cortical atrophy and FC alterations, suggesting that cortical thickness and FC may be neuroimaging-based diagnostic biomarkers for PD-MDD.

Association between levels of high-sensitivity C-reactive protein in plasma and freezing of gait in Parkinson's disease.

This study explored the potential relationship between levels of high-sensitivity C-reactive protein (hs-CRP) in plasma and freezing of gait (FOG) in Parkinson's disease (PD) in China. A total of 72 healthy subjects, 62 PD patients with FOG, and 83 PD patients without FOG from our center were enrolled in this prospective study. Patients with FOG showed significantly higher hs-CRP levels than controls, but patients without FOG did not. Binary logistic regression analysis identified levels of hs-CRP in plasma to be an independent risk factor for FOG among the patients in our cohort (OR 6.371, 95% CI 2.589-15.678, p < 0.001). In fact, a cut-off level of 0.935 mg/L distinguished patients with or without FOG [area under the ROC curve (AUC) = 0.908, sensitivity 87.1%, specificity 89.2%]. Our study suggests that high levels of hs-CRP in plasma are associated with the occurrence of FOG in PD. The pooled data combined with a previous study carried out in Spain also indicate a positive association between plasma hs-CRP levels and FOG in PD. However, more research is still needed to verify the plasma hs-CRP as a potential biomarker of FOG.

Downregulation of CHCHD2 may Contribute to Parkinson's Disease by Reducing Expression of NFE2L2 and RQCD1.

BACKGROUND: Parkinson's disease (PD) is associated with coiled-coil-helix-coiled-coilhelix domain containing 2 (CHCHD2) downregulation, which has been linked to reduced cyclocytase activity and increased levels of oxygen free radicals, leading to mitochondrial fragmentation and apoptosis. Little is known about how CHCHD2 normally functions in the cell and, therefore, how its downregulation may contribute to PD. OBJECTIVE: This study aimed to identify such target genes using chromatin immunoprecipitation sequencing from SH-SY5Y human neuroblastoma cells treated with neurotoxin 1-methyl-4- phenylpyridinium (MPP+) as a PD model. METHODS: In this study, we established a MPP+ -related SH-SY5Y cell model and evaluated the effects of CHCHD2 overexpression on cell proliferation and apoptosis. At the same time, we used high-throughput chromatin immunoprecipitation sequencing to identify its downstream target gene in SH-SY5Y cells. In addition, we verified the possible downstream target genes and discussed their mechanisms. RESULTS: The expression level of α-synuclein increased in SH-SY5Y cells treated with MPP+, while the protein expression level of CHCHD2 decreased significantly, especially after 24 h of treatment. Chip-IP results showed that CHCHD2 might regulate potential target genes such as HDX, ACP1, RAVER2, C1orf229, RN7SL130, GNPTG, erythroid 2 Like 2 (NFE2L2), required for cell differentiation 1 homologue (RQCD1), solute carrier family 5 member 7 (SLA5A7), and NAcetyltransferase 8 Like (NAT8L). NFE2L2 and RQCD1 were validated as targets using PCR and western blotting of immunoprecipitates, and these two genes together with SLA5A7 and NAT8L were upregulated in SH-SY5Y cells overexpressing CHCHD2. Downregulation of CHCHD2 may contribute to PD by leading to inadequate expression of NFE2L2 and RQCD1 as well as, potentially, SLA5A7 and NAT8L. CONCLUSION: Our results suggest that CHCHD2 plays a protective role by maintaining mitochondrial homeostasis and promoting proliferation in neurons. In this study, the changes of CHCHD2 and downstream target genes such as NFE2L2/RQCD1 may have potential application prospects in the future. These findings provide leads to explore PD pathogenesis and potential treatments.

Development and validation of a nomogram for freezing of gait in patients with Parkinson's Disease.

OBJECTIVES: Freezing of gait (FOG) is a common and complex disabling episodic gait disturbance in patients with Parkinson's disease (PD). Currently, the treatment of FOG remains a challenge for clinicians. The aim of our study was to develop a nomogram for FOG risk based on data collected from Chinese patients with PD. MATERIALS & METHODS: A total of 379 PD patients (197 with FOG) from Kunming Medical University were recruited as a training cohort. Additionally, 339 PD patients (166 with FOG) were recruited from West China Hospital of Sichuan University, to serve as the validation cohort. The least absolute shrinkage and selection operator regression model was used to select clinical and demographic characteristics as well as blood markers, which were incorporated into a predictive model using multivariate logistic regression to predict the risk of developing FOG. The model was validated using the validation dataset, and model performance was evaluated using the C-index, calibration plot, and decision curve analyses. RESULTS: The final predictive model included the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score, Parkinson's Disease Questionnaire (PDQ39), H-Y stage, and visuospatial function. The model showed good calibration and good discrimination, with a C-index value of 0.772 against the training cohort and 0.766 against the validation cohort. Decision curve analysis demonstrated the clinical utility of the nomogram. CONCLUSION: A nomogram incorporating RBDSQ, PDQ39, H-Y stage, and visuospatial function may reliably predict the risk of FOG in PD patients.

Plasma neurofilament light chain levels are associated with depressive and anxiety symptoms in Parkinson's disease.

The present study aimed to explore the association of plasma neurofilament light chain (NfL) levels with depression and anxiety in Parkinson's disease (PD). This prospective study enrolled 116 patients with PD and 38 healthy controls, and found plasma NfL levels were higher in patients with depression or anxiety than in those without these symptoms. Binary logistic regression identified NfL concentration as an independent predictor of depression and anxiety in PD. In conclusion, elevated plasma NfL may be associated with severity of depression and anxiety in PD patients and may serve as a diagnostic biomarker of PD with moderate to severe depression or anxiety.

REM sleep behavioral disorder may be an independent risk factor for orthostatic hypotension in Parkinson's disease.

PURPOSE: The purpose of this study was to evaluate the association between clinically possible rapid eye movement (REM) sleep behavioral disorder (pRBD) and orthostatic hypotension (OH) in PD patients, as well as to explore the mechanisms underlying the association. METHODS: PD patients (n = 116) were assigned to a group with OH (PD-OH) or without OH (PD-NOH). General demographic and clinical data were collected. A series of scales were used to assess the clinical symptoms in the two groups. RESULTS: A total of 27 patients (23.3%) had OH. The PD-OH group showed significantly higher H-Y staging score and significantly higher frequencies of pRBD, anxiety, depression, and cognitive impairment than the PD-NOH group. Binary logistic regression analysis identified the following factors as independently associated with PD-OH: H-Y staging [odds ratio (OR) 2.565, 95% confidence interval (CI) 1.160-5.673; P = 0.020], RBD (OR 7.680, 95% CI 1.944-30.346; P = 0.004), UPDRS II (OR 1.021, 95% CI 0.980-1.063; P = 0.020), depression (OR 7.601, 95% CI 1.492-38.718; P = 0.015), and cognitive impairment (OR 0.824, 95% CI 0.696-0.976; P = 0.025). CONCLUSIONS: Our results suggest that pRBD is an independent risk factor for OH in patients with PD. We speculate that there may be a close relationship between RBD and OH, which requires attention. Early diagnosis of RBD may help predict the appearance of OH in PD patients.

Construction and analysis of a competing endogenous RNA network associated with circRNAs dysregulated in medial temporal lobe epilepsy.

The aetiology and pathogenesis of medial temporal lobe epilepsy (MTLE) remain unclear, and effective treatments are lacking. The involvement of a dysregulated competing endogenous RNA (ceRNA) network in MTLE is only partially understood. The purpose of this study was to investigate MTLE regulatory networks composed of messenger RNAs (mRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) through a ceRNA network map. RNA sequencing (RNA-seq) and small RNA-seq were used to detect mRNAs, circRNAs, miRNAs, and lncRNAs differentially expressed between post-operation hippocampal tissues of MTLE patients (n = 3) and paracancer tissues (n = 3). We performed bioinformatics analysis to identify differentially expressed RNAs and construct the corresponding ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed RNAs were conducted to explore the biological processes and pathways involved in MTLE. We identified 352 differentially expressed mRNAs, 179 circRNAs, and 42 miRNAs in MTLE. A ceRNA network composed of mRNAs, circRNAs, and miRNAs was constructed. GO and KEGG analysis of the network suggested a key role of synapses and mTOR, cAMP, ErbB, FoxO, and HIF-1 signalling pathways in MTLE. We identify a new circRNA-miRNA-mRNA ceRNA network in MTLE. These results can help clarify the aetiology of MTLE and identify targeted molecular therapies.

Resting-state functional magnetic resonance imaging of the cerebellar vermis in patients with Parkinson's disease and visuospatial disorder.

PURPOSE: Visuospatial disorders (VSDs) are common in Parkinson's disease (PD). VSDs may involve cerebellar vermis, but evidence from functional connectivity (FC) studies is lacking. Here we compared FC between cerebellar vermis and the entire brain between PD patients with or without VSD, and between patients and healthy controls. METHODS: Resting-state 3.0-T functional magnetic resonance imaging was performed on 19 controls, 31 PD patients with VSD and 12 PD patients without VSD. Correlations in brain network were calculated between eight regions of interest in the cerebellar vermis (I-VIII) and other voxels in the brain, and voxel-based FC was analyzed. Patients were assessed in terms of cognitive function as well as motor and non-motor symptoms. RESULTS: In both types of patients, cerebellar vermis VIII, IX and X showed positive FC with the default-mode network (DMN), executive control network and sensorimotor network. Cerebellar vermis I and II showed positive FC with the visual network and DMN in controls, but negative FC in PD patients without VSD. Cerebellar vermis X showed negative FC with lobules VIII and IX of the left cerebellar hemisphere in controls, but positive FC in PD patients with VSD. CONCLUSION: Positive FC connecting the cerebellar vermis VIII and X with associated brain networks in PD patients with VSD may be compensatory activation. PD may involve disruption of functional coupling between the cerebellar vermis and cerebral cortex.