Olfactory dysfunction is a well‐recognized prodromal sign of Parkinson’s disease (PD). This study aimed to explore the potential of short‐form olfactory tests as a more convenient method for assessing PD symptoms in clinical practice. This retrospective cross‐sectional study included 176 patients with PD. For each clinical measure, 40 separate logistic regression models evaluated its association with correct identification of each UPSIT‐TC odor. Odors showing nominal associations at unrounded p < 0.05 were designated candidate symptom‐associated odors. A symptom‐specific odor score was constructed when at least two odors (≥ 2) met this criterion. Associations of each clinical measure with the UPSIT‐TC total score and its corresponding symptom‐specific odor score were subsequently evaluated using correlation analyses and covariate‐adjusted regression models. Across all clinical measures, 101 nominal odor–clinical associations involving 31 unique odors were identified, with 17 clinical measures meeting the ≥ 2‐odor criterion. Symptom‐specific odor scores generally showed stronger unadjusted correlations with their corresponding clinical measures than did the UPSIT‐TC total score. After adjustment for age, sex, disease duration, and levodopa equivalent daily dose (LEDD), with false discovery rate correction across 32 models, symptom‐specific odor scores remained significantly associated with MDS‐UPDRS total and Parts I–III scores, bradykinesia, rigidity, axial symptoms, NMSS total and gastrointestinal and urinary domain scores, MoCA scores, and NPI total scores. In contrast, the UPSIT‐TC total score remained significantly associated only with rigidity. Symptom‐specific odor scores have the potential to serve as a more clinically practical tool for assessing PD symptom burden than the UPSIT‐TC total score. Further large‐scale, multicenter studies are needed to explore odors with higher specificity for PD clinical symptoms.
Respiratory disorders significantly impair functional baseline and quality of life (QoL) in Parkinson’s disease (PD). This cross-sectional study aimed to evaluate spirographic lung function parameters in PD and determine their relationships with motor and nonmotor symptoms, QoL, and dopaminergic therapy. Spirometric parameters were recorded in 57 outpatients with PD and 10 healthy controls. PD patients underwent clinical assessments using UPDRS Parts II and III, Schwab and England scale, PDQ-39, and PFS-16. Spirometric analysis revealed significant decreases in VC %pred in PD patients versus controls, and in FVC %pred in PD Stage III versus PD Stage II. Decreased lung function correlated with H&Y stage (VC, FVC, FEV1) and showed inverse correlations with UPDRS Parts II and III scores, most pronounced for axial-locomotor impairments (posturing, gait, stability, arising from chair) and bradykinesia. PFS-16 fatigue index inversely correlated with FEV1 and PEF. Worse QoL (PDQ-39 summary index, emotional well-being, and cognition domains) was primarily coupled with decreased expiratory flow rates (FEV1, PEF). Untreated PD patients exhibited significantly lower FVC%pred, FEV1%pred, FEF75%pred, and Tiffeneau index than those on dopaminergic therapy. This study demonstrates the presence of respiratory dysfunction in PD Stages II and III and its negative association with QoL. The results highlight the relationship between lung function decline and overall PD progression, with the strongest associations revealing the most significant contribution of postural abnormalities, bradykinesia, and pathological fatigue. Furthermore, the obtained data suggest a potential compensating role of dopaminergic therapy.
Background Numerous studies have sought to investigate the link between obesity and Parkinson’s disease (PD), yielding conflicting results. Relative fat mass (RFM) is a novel obesity indicator, yet its association with PD in American adults remains unexplored. This study was designed to explore the potential relationship between RFM and PD in American adults aged 40 and older. Methods In the present study, we ultimately included 26, 029 participants from the NHANES (1999–2018). In order to evaluate the association between RFM and PD in American adults aged 40 and older, we performed multivariate logistic regression analysis, restricted cubic spline analysis, subgroup analysis, and sensitivity analysis. Furthermore, we conducted receiver operating characteristic (ROC) curve analysis to evaluate the predictive performance of RFM for PD. Results Of the 26, 029 participants who were included in the study, 245 participants (0.94%) were identified as having PD. After full adjustment for confounding variables, the multivariate models demonstrated a significant positive association between RFM and PD (odds ratio [OR] = 1.40; 95% confidence interval [CI] = 1.11 – 1.77). Specifically, participants in the highest RFM quartile (Q4) had a significantly higher prevalence of PD compared with those in the lowest quartile (Q1) in model II (OR = 2.71, 95% CI: 1.48–4.96). Additionally, subgroup analyses demonstrated that the positive correlation between RFM and PD was significantly more prominent in individuals under the age of 60 ( p for interaction < 0.05). Finally, ROC curve analysis showed that RFM yielded a higher AUC value of 0.612 in participants under the age of 60. Conclusions This study is the first to demonstrate a positive linear association between RFM and PD among American adults aged 40 and older.
Background Motor fluctuations often occur with long‐term levodopa treatment in Parkinson’s disease (PD). Safinamide is a drug that inhibits monoamine oxidase B (MAO‐B) and modulates glutamate. It is used together with levodopa. A summary of the latest evidence is needed to assess its effectiveness and safety. Objective To assess the effectiveness and safety of safinamide as an additional therapy to levodopa for motor fluctuations in PD. Methods A systematic review and meta‐analysis followed PRISMA guidelines. A thorough literature search was done from the beginning until January 2026 across PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. We included randomized controlled trials (RCTs) that compared safinamide (100 mg/day) to placebo as an addition to levodopa in adults with PD and motor fluctuations. The primary effectiveness outcomes were the change in daily OFF‐time (in hours) and the Unified Parkinson’s Disease Rating Scale Part III (UPDRS‐III) score. The main safety outcome was the occurrence of dyskinesia. We assessed the risk of bias using the Cochrane RoB 2 tool. Data were combined using random‐effects models, with results shown as mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CIs). We evaluated the certainty of evidence using GRADE. The protocol was registered with PROSPERO (CRD420261298124). Results Three RCTs ( N = 1127 participants) were included. Safinamide 100 mg significantly reduced daily OFF‐time compared to placebo, with an MD of −1.21 h (95% CI: −1.60 to −0.82; I 2 = 39%; moderate certainty). It also significantly improved motor function, as shown by the UPDRS‐III MD of −3.13 points (95% CI: −4.89 to −1.37; I 2 = 72%; low certainty). However, safinamide increased the risk of dyskinesia, with a RR of 3.01 (95% CI: 1.92 to 4.70; I 2 = 0%; moderate certainty). In a secondary analysis of the Hattori trial’s 50 mg arm ( n = 131), safinamide 50 mg reduced OFF‐time by −1.25 h (95% CI: −1.92 to −0.58) and improved the UPDRS‐III by −4.06 points (95% CI: −5.54 to −2.59). This effect was smaller for OFF‐time compared to the 100‐mg dose, suggesting a potential dose–response relationship that warrants further investigation. Conclusion Safinamide 100 mg per day appears to be a helpful addition to levodopa for reducing OFF‐time and improving motor function in PD patients with motor fluctuations. However, this benefit comes with a higher risk of dyskinesia, so careful patient selection and monitoring are important. The 50‐mg dose shows similar but less pronounced effects, supporting 100 mg as the preferred dose. Further research is needed to confirm these findings.
Background Accumulating evidence implicates peripheral immune dysregulation in the pathogenesis of Parkinson’s disease (PD). High‐mobility group box 1 (HMGB1), a key alarmin released during mitochondrial stress, has been reported to be upregulated in the peripheral blood of PD patients, yet its precise role remains unclear. Methods We performed an integrated analysis of multiple transcriptomic datasets from peripheral blood mononuclear cells (PBMCs) of PD patients. Using a combination of methods including machine learning, cell–cell communication analysis, in silico gene perturbation, and pathway enrichment analysis, we systematically investigated the expression and regulation of HMGB1 in peripheral immune cells in PD. Results We found that HMGB1 mRNA expression was significantly downregulated in PBMCs from PD patients. A machine learning model identified HMGB1 as a potential predictive signature (AUC = 0.685). Single‐cell transcriptomic analysis revealed immune cell heterogeneity and identified CD8 + T and CD4 + T cells as central hubs in the cellular communication network. In silico perturbation analysis suggested that HMGB1 may be associated with the expression of S100A8 and S100A9 , which are enriched in the IL‐17 signaling pathway. Drug enrichment analysis identified potential therapeutic agents, including TPEN, hydrocotarnine, and phorbol 12‐myristate 13‐acetate. Conclusion Our analysis revealed a distinct downregulation of HMGB1 within the peripheral immune compartment of PD, a change that was decoupled from the overall proinflammatory state. Observing the concomitant upregulation of the S100 gene family and activation of the IL‐17 pathway, we propose a putative pathogenic axis based on computational findings: HMGB1 downregulation is linked to S100 gene family upregulation and IL‐17 pathway activation.
