Zhongbao Gao

Parkinson’s disease (PD) significantly impacts motor function and psychosocial wellbeing, with exercise rehabilitation being vital for symptom management. However, limited understanding of its benefits among patients and their families hampers adherence. This study explored the perceived knowledge, attitudes, and practices (KAP) related to exercise rehabilitation in PD across China. A cross-sectional survey was conducted from September 1 to October 21, 2024, involving 1,082 responses from patients and families across 27 provinces, using a self-designed questionnaire. Participants had a mean age of 51.64 years; 53.2% were male. The average KAP scores were 12.72 for perceived knowledge, 27.59 for attitude, and 49.37 for practice. Significant positive correlations were found among the KAP dimensions, with perceived knowledge showing strong associations with attitude and practice. Mediation analysis indicated that perceived knowledge was directly and indirectly associated with practice through attitude, suggesting its important role in rehabilitation-related behaviors. Overall, PD patients and their families demonstrated moderate perceived knowledge and positive attitudes toward exercise rehabilitation. Enhanced targeted education could improve understanding, thereby promoting better practices, which may lead to improved disease management and patient outcomes.

Brain structure characteristics form the basis on regulating neuroplastic processes by genes, and structural alterations may contribute to the progression of Parkinson’s disease (PD) and their divergent clinical manifestations. However, the neural mechanisms underlying the relations between the genetic signatures to structural alterations in PD patients are unclear. This study aimed to integrate alterations in cortical thickness and subcortical nuclei volume (thalamus, hippocampus, and amygdala) in PD, and to explore global cortical thickness differences associated with gene function. 7-Tesla magnetic resonance imaging scans were obtained for 98 patients with PD and 74 healthy controls (HC). Cortical thickness and subcortical nuclei volume were extracted based on FreeSurfer and were analyzed using general linear model to find significant differences between two groups. Regression model was used for cross-sectional the impact of structural alterations on motor signs as well as non-motor symptoms. Gene-imaging association analysis was used to characterize its gene signatures. Compared with HC, PD patients exhibited the disease-specific structural pattern, characterized by reduced cortical thickness in the right pars triangularis and altered volumes of specific nuclei subfields. Moreover, the Cornu Ammonis 1 head volume was significantly correlated with rigidity scores. Using human brain gene expression data, genes identified in this study were enriched for ribosome and synaptic organization and explain significant variation in global cortical thickness differences. Taken together, these findings may contribute to a better understanding of neural mechanisms in PD and the functional roles of genes that influence brain structure.

Background: Dopamine replacement therapy is a cornerstone of Parkinson’s disease treatment. In clinical practice, there is considerable variability in patients’ responses, tolerability, and safety regarding anti-parkinsonian medications, which is largely influenced by genetic polymorphisms in pharmacokinetic and pharmacodynamic genes. However, the application of multigenetic pharmacogenomics-guided treatment (MPGT) to optimize therapeutic outcomes in Parkinson’s disease (PD) remains under-explored. In this study, we conducted a prospective cohort investigation to evaluate the potential benefits of MPGT on motor symptoms in PD patients.Methods: A total of 28 patients with PD were followed for 4 weeks. Among them, 22 patients underwent multigenetic pharmacogenomic testing, with 13 receiving treatments based on the test results (MPGT group). The remaining 15 received standard care (TAU group). Baseline characteristics, as well as changes in Unified Parkinson’s Disease Rating Scale (UPDRS) III scores and sub-scores, were compared between the two groups. Associations between various single nucleotide polymorphisms (SNPs) and treatment outcomes were analyzed using generalized linear models.Results: At the 4-week follow-up, the MPGT group showed significantly greater reductions in UPDRS III total scores (p < 0.05) and limb sub-scores (p < 0.01) compared to the TAU group. These differences remained significant after adjusting for increases in levodopa equivalent daily dose (p = 0.011 and p = 0.002, respectively) and piribedil use (p = 0.006 and p = 0.004, respectively). Patients homozygous for the major allele of rs4984241 (AA vs. AG+GG, p = 0.003), rs4680 (GG vs. GA+AA, p = 0.013), rs1076560/rs2283265 (CC vs. AC+AA, p = 0.039) and rs622342 (AA vs. AC, p = 0.043) showed greater improvement in total UPDRS III, postural instability and gait difficulty (PIGD), rigidity and tremor scores, respectively, compared to those carrying at least one minor allele.Conclusion: MGPT demonstrates significant potential as a valuable tool for personalized treatment in PD patients. Additionally, we identified several SNPs associated with the responsiveness to chronic administration of multiple anti-parkinsonian drugs. However, to confirm these findings, well-designed studies with larger, well-characterized samples are necessary.

Background: It is well known that dysfunction of thalamocortical circuity generates the motor signs that lead to distinct disease processes and prognoses in Parkinson’s disease (PD). This study aimed to leverage ultrahigh-field magnetic resonance imaging (MRI) to identify the connectivity alterations of thalamocortical circuity and clarify their relation to motor signs in early PD. Methods: Patients with early-stage PD (n=55) and healthy controls (HCs, n=56) were recruited from March 2022 to July 2023. All participants underwent 7-Tesla MRI scans as the baseline. Sign scores were calculated from the Movement Disorder Society Unified Parkinson’s Disease Rating Scale III. Significant differences in the functional connectivity between the thalamus subregions and cortex between the PD and HC groups were discovered. The association between altered thalamic functional connectivity and sign scores was evaluated using Spearman or Pearson correlation analysis with false discovery rate (FDR) correction. Results: Compared to the HCs, the patients with early-stage PD exhibited a decreased functional connectivity between thalamic subregions (primary motor, sensory, occipital, premotor, and parietal thalamus regions) and the cortex [voxel-level Pfamily-wise error (FWE) FDR =0.049) and the right thalamus (r=–0.267; P_FDR =0.048) . Conclusions: These findings support the use of ultrahigh-field MRI for examining the thalamic subregions and clarifying their involvement in the neural mechanisms of various motor signs in early-stage PD.

Parkinson’s disease (PD) is a common neurodegenerative disorder, and neuroinflammation plays a pivotal role in its pathogenesis. T-cell immunoglobulin and mucin-domain-containing molecule 3 (Tim-3) is a crucial immunoregulatory mediator in various diseases; however, its roles and underlying molecular mechanisms in PD remain unclear. We established in vitro and in vivo 1-methyl-4-phenylpyridinium (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD models in Tim-3–knockout BV2 cells and mice, respectively. Motor function was assessed through behavioral tests, including pole, traction, forced swimming, and open field tests. Immunofluorescence was used to examine dopaminergic neuron loss and glial activation. The expression levels of nuclear factor-kappa B (NF-κB)/nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) pathway components were evaluated by western blotting. Proinflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA). Compared with the wild-type, Tim-3 expression was significantly increased in the PD model, and Tim-3 deficiency mitigated MPTP-induced motor deficits, dopaminergic neuron loss, and glial cell activation. Furthermore, Tim-3 deficiency suppressed neuroinflammation by negatively modulating the NF-κB/NLRP3 pathway, thereby downregulating the expression of the proinflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α. These findings indicate that Tim-3 plays a proinflammatory role in PD by regulating the NF-κB/NLRP3 pathway, highlighting Tim-3 as a promising therapeutic target for PD.

Background: Previous epidemiological studies have reported an association between Sjögren’s syndrome (SS) and Parkinson’s disease (PD); however, the causality and direction of this relationship remain unclear. In this study, we aimed to investigate the causal relationship between genetically determined SS and the risk of PD using bidirectional Mendelian randomization (MR).Methods: Summary statistics for Sjögren’s syndrome used as exposure were obtained from the FinnGen database, comprising 1,290 cases and 213,145 controls. The outcome dataset for PD was derived from the United Kingdom Biobank database, including 6,998 cases and 415,466 controls. Various MR methods, such as inverse variance weighted (IVW), Mendelian randomization Egger regression (MR-Egger), weighted median (WM), simple mode, weighted mode, MR-pleiotropy residual sum and outlier (MR-PRESSO), and robust adjusted profile score (RAPS), were employed to investigate the causal effects of SS on PD. Instrumental variable strength evaluation and sensitivity analyses were conducted to ensure the reliability of the results. In addition, reverse MR analysis was performed to examine the causal effects of PD on SS.Results: The WM, IVW, RAPS and MR-PRESSO methods demonstrated a significant association between genetically predicted SS and reduced risk of PD (odds ratio OR_WM = 0.9988, OR_IVW = 0.9987, OR_RAPS = 0.9987, OR_MR-PRESSO = 0.9987, respectively, P < 0.05). None of the MR analyses showed evidence of horizontal pleiotropy (P > 0.05) based on the MR-Egger and MR-PRESSO tests, and there was no statistical heterogeneity in the test results of the MR-Egger and IVW methods. The leave-one-out sensitivity analysis confirmed the robustness of the causal relationship between SS and PD. Furthermore, reverse MR analysis did not support any causal effects of PD on SS.Conclusion: Our MR study supports a potential causal association between SS and a reduced risk of PD. Further extensive clinical investigations and comprehensive fundamental research are warranted to elucidate the underlying mechanisms linking SS and PD.

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disease and affects millions of people. Accurate diagnosis and subsequent treatment in the early stages can slow down disease progression. However, making an accurate diagnosis of PD at an early stage is challenging. Previous studies have revealed that even for movement disorder specialists, it was difficult to differentiate patients with PD from healthy individuals until the average modified Hoehn-Yahr staging (mH&Y) reached 1.8. Recent researches have shown that dysarthria provides good indicators for computer-assisted diagnosis of patients with PD. However, few studies have focused on diagnosing patients with PD in the early stages, specifically those with mH&Y ≤ 1.5.Method: We used a machine learning algorithm to analyze voice features and developed diagnostic models for differentiating between healthy controls (HCs) and patients with PD, and for differentiating between HCs and patients with mild PD (mH&Y ≤ 1.5). The models were independently validated using separate datasets.Results: Our results demonstrate that, a remarkable diagnostic performance of the model in identifying patients with mild PD (mH&Y ≤ 1.5) and HCs, with area under the ROC curve 0.93 (95% CI: 0.851.00), accuracy 0.85, sensitivity 0.95, and specificity 0.75.Conclusion: The results of our study are helpful for screening PD in the early stages in the community and primary medical institutions where there is a lack of movement disorder specialists and special equipment.