BACKGROUND:Early differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD) remains difficult, particularly within two years of symptom onset, when diagnostic uncertainty has major implications for prognosis, referral, and trial enrolment. Because MSA is rare, previous biomarker studies have often been limited by relatively small samples and restricted multicentre validation. We aimed to determine the diagnostic performance of plasma neurofilament light chain (NfL) for differentiating MSA from PD and to assess the incremental value of glial fibrillary acidic protein (GFAP), total tau (t-tau), and phosphorylated tau at threonine 217 (p-tau217). METHODS:In this multicentre cross-sectional diagnostic study, participants were enrolled from five movement-disorder referral centres in China between Jan 1, 2018, and June 30, 2024, and were divided by enrolment period into discovery and temporally separated validation datasets. Plasma NfL, GFAP, t-tau, and p-tau217 were measured using light-initiated chemiluminescence assays. Group comparisons used age- and sex-adjusted models, and discrimination was assessed using receiver-operating-characteristic analysis with sensitivity, specificity, predictive values, and robustness analyses. FINDINGS:The analysis included 2408 participants: 782 (32.5%) with PD, 796 (33.1%) with MSA, and 830 (34.5%) healthy controls. NfL was the best single biomarker for differentiating MSA from PD in the discovery dataset (AUC 0.920, 95% CI 0.903-0.936). The discovery-derived cutoff of 41.3 pg/mL yielded sensitivity of 90.5% and specificity of 83.4% in the discovery dataset, and sensitivity of 86.7% and specificity of 85.5% in the validation dataset (AUC 0.924, 95% CI 0.898-0.948). In the early-stage subgroup, NfL retained strong performance (AUC 0.943, 95% CI 0.915-0.966). Integrated multimarker models provided limited incremental discrimination over NfL alone. INTERPRETATION:Plasma NfL may support the differentiation between clinically diagnosed MSA and PD, including early in the disease course. The limited added value of multimarker panels supports a simpler and more immediately translatable NfL-first strategy for diagnostically uncertain parkinsonism. FUNDING:National Natural Science Foundation of China; the Capital's Fund for Health Improvement and Research; Beijing Natural Science Foundation; Beijing Municipal Science and Technology Commission; Beijing Neurosurgical Institute; Beijing Traditional Chinese Medicine Science and Technology Development Fund.

The diagnosis of progressive supranuclear palsy (PSP) remains challenging, particularly in differentiating it from Parkinson's disease (PD) at early stages. Circulating neuron-derived extracellular vesicles (NDEVs) providing a peripheral window into central nervous system pathology may serve as promising biomarkers. A total of 188 participants were recruited from 3 centers. A discovery cohort (40 PSP patients, 36 PD patients, and 31 healthy controls [HCs]) and a multicenter validation cohort (30 PSP patients, 27 PD patients, and 24 HCs) were established. NDEVs containing total tau, 4R tau, phosphorylated tau (ptau181, ptau217, ptau231 and ptau396) in plasma samples were analyzed using nano-scale flow cytometry. Multivariable logistic regression models were developed in the discovery cohort and strictly validated in the independent cohort using fixed model parameters. In the discovery cohort, the concentrations of tau, 4R tau, ptau181, and ptau217-containing NDEVs in PSP patients were significantly higher than those in HCs and PD patients, while ptau396-containing NDEVs showed elevation exclusively in PSP compared to HCs. (PSP vs. HCs: P<0.001 for tau, P<0.001 for 4R tau, P<0.001 for ptau181, P=0.008 for ptau217, P=0.009 for ptau396; PSP vs. PD: P<0.001 for tau, P<0.001for4R tau, P=0.029 for ptau181, P=0.003 for ptau217). An integrated model incorporating these biomarkers achieved an area under the curve (AUC) of 0.965 (90.0% sensitivity, 96.8% specificity) for distinguishing PSP from HCs, and an AUC of 0.963 (87.5% sensitivity, 94.4% specificity) for distinguishing PSP from PD. In the validation cohort, the concentrations of tau, 4R tau, ptau181, ptau217, and ptau396-containing NDEVs in plasma were significantly higher in PSP patients compared to HCs (PSP vs. HCs: P<0.001 for tau, 4R tau, and ptau217, P=0.03 for ptau181, P=0.017 for ptau396). Similarly, the concentrations of tau, 4R tau, ptau181, and ptau217 were higher in PSP patients than in PD patients (PSP vs. PD: P<0.001 for tau, 4R tau, and ptau217, P=0.025 for ptau181). The integrated model yielded an AUC of 0.971 for distinguishing PSP from HCs and 0.990 for distinguishing PSP from PD. Notably, in early-stage patients, the integrated model achieved an AUC of 0.987 in differentiating early-stage PSP from PD. These findings indicate that plasma tau-species-containing NDEVs are promising biomarkers for PSP, offering high sensitivity and specificity for distinguishing PSP from both HCs and PD, particularly in early disease stages. Further large-scale, longitudinal studies are warranted to fully validate these findings and explore their role in PSP pathophysiology and progression.

Parkinson's disease (PD) is characterized by nigrostriatal dopaminergic degeneration, which can be mapped in vivo using dopamine transporter (DAT) imaging. While elevated blood neurofilament light chain (NfL) indicates neuroaxonal injury in PD, the extent to which peripheral NfL reflects the specific spatial pattern of nigrostriatal dopaminergic terminal loss remains unresolved. This study investigated whether blood NfL tracks region-specific DAT availability and whether this coupling exhibits anatomical heterogeneity related to disease stage. We studied 87 patients with PD from Beijing Tiantan Hospital who underwent 11C-CFT PET and plasma measurement of NfL, glial fibrillary acidic protein (GFAP) and total tau (t-tau). Whole-brain voxelwise mapping and prespecified regional and subregional analyses tested associations between biomarkers and DAT availability, adjusted for age, sex, disease duration and motor severity. External replication used Parkinson’s Progression Markers Initiative (PPMI) data: 550 patients with baseline serum NfL and 123I-FP-CIT single-photon emission computed tomography, 381 with 2-year follow-up data, and a cerebrospinal fluid (CSF) subcohort of 207 patients at baseline and 185 at 2 years. In the Tiantan cohort, higher plasma NfL was associated with lower 11C-CFT PET signal in spatially coherent basal ganglia and nigrostriatal clusters, whereas GFAP and t-tau showed weaker and less coherent patterns. Region of interest (ROI) analyses confirmed inverse NfL-DAT associations in the putamen, globus pallidus and nucleus accumbens. Subregional analyses revealed stronger coupling in the anterior than posterior putamen (β = -0.48 versus -0.32; interaction q = 0.037) and significant heterogeneity across pallidal subdivisions. Disease-duration stratification showed that posterior putaminal coupling was attenuated after the first year, whereas anterior putaminal coupling persisted, consistent with reduced dynamic range in regions of advanced terminal depletion. In the PPMI cohort, serum NfL showed inverse associations with dopamine transporter specific binding ratios at baseline in the caudate and anterior putamen and at 2 years in the caudate, putamen and anterior putamen. CSF NfL associations emerged at 2 years, particularly in the putamen and anterior putamen. Peripheral neurofilament light chain is anatomically coupled to nigrostriatal dopamine transporter loss in PD, with subregional heterogeneity shaped by dopaminergic reserve and disease duration. These findings support blood NfL as a complementary, scalable biomarker of active nigrostriatal neuroaxonal injury and a candidate stratification covariate for biomarker-informed PD studies.

There are multiple cerebrospinal fluid (CSF) biomarkers with potential for distinguishing Parkinson’s disease (PD) from atypical parkinsonian syndromes (APSs) and controls; however, consensus on their diagnostic performance remains limited. This study aims to systematically evaluate and rank the diagnostic accuracy of CSF biomarkers in differentiating PD from APS and controls through network meta-analysis, determining the clinical diagnostic yield of these biomarkers and whether they should be considered as first-line diagnostic and differentiating tools. A comprehensive research was performed on PubMed, Web of Science, Embase and Cochrane library from inception until December 31st, 2024. Random effects models for sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95

Objectives: Levodopa remains the most effective treatment for Parkinson’s disease (PD); however, tremor reactions to dopaminergic medications show significant variance among patients with PD. This study aimed to assess the different methodologies employed to determine the dopamine responsiveness of tremors and their association with the clinical characteristics of PD. Methods: Patients with PD and tremors were evaluated using the acute levodopa challenge test (LCT). Tremor levodopa responsiveness (LR) was calculated using the Unified Parkinson’s Disease Rating Scale Part III (UPDRS‐III) scores during OFF and ON periods. Tremor LR was calculated in two formats: absolute difference in tremor scores (OFF–ON), termed aLR, and percentage change in tremor scores, termed %LR and calculated as ([OFF–ON]/OFF100%). Independent variables were compared between the better tremor response to levodopa and poorer tremor response to levodopa groups based on the tremor change rate median score. Additionally, the effect of the tremor LR calculation method was correlated with clinical measures. Results: This study enrolled 188 patients with PD who displayed tremors, of whom 98 (52%) showed better tremor response to levodopa. We identified a moderately negative correlation between tremor aLR and the rigidity‐to‐tremor score ratio ( r = 0.40) during the OFF period, in addition to positive correlations between tremor aLR and the tremor score ( r = 0.75), rest tremor score ( r = 0.75), motor score ( r = 0.42), postural and kinetic tremor score ( r = 0.30), and tremor score‐to‐disease duration ratio ( r = 0.30) of the UPDRS‐III during OFF periods. The tremor %LR showed no significant relationship with any of the tested variables. Conclusions: The aLR, rather than the %LR, is a more effective assessment method for evaluating the efficacy of levodopa for treating tremors in PD.

Early and precise diagnosis of α-synucleinopathies is challenging but critical. In this study, we developed a molecular beacon-based assay to evaluate microRNA-containing extracellular vesicles (EVs) in plasma. We recruited 1203 participants including healthy controls (HCs) and patients with isolated REM sleep behavior disorder (iRBD), α-synucleinopathies, or non-α-synucleinopathies from eight centers across China. Plasma miR-44438-containing EV levels were significantly increased in α-synucleinopathies, including those in the prodromal stage (e.g., iRBD), compared to both non-α-synucleinopathy patients and HCs. However, there are no significant differences between Parkinson's disease (PD) and multiple system atrophy. The miR-44438-containing EV levels negatively correlated with age and the Hoehn and Yahr stage of PD patients, suggesting a potential association with disease progression. Furthermore, a longitudinal analysis over 16.3 months demonstrated a significant decline in miR-44438-containing EV levels in patients with PD. These results highlight the potential of plasma miR-44438-containing EV as a biomarker for early detection and progress monitoring of α-synucleinopathies.

目的 探讨早发型帕金森病患者外周红细胞α-突触核蛋白水平是否存在特异性改变.方法 纳入 47 例早发型帕金森病患者,52 例健康受试者.采集受试者外周静脉血标本并分离红细胞,用电化学发光免疫法检测红细胞中α-突触核蛋白水平.对其中 25 例早发型帕金森病患者进行随访,2 年后再次采集静脉血标本和临床评估.结果 早发型帕金森病患者红细胞总体和聚集体形式的α-突触核蛋白水平均显著高于健康对照组[总体 1.28(0.94,2.13)vs 0.57(0.41,0.70),P＜0.001;聚集体202.18(152.16,244.22)vs 128.40(107.61,157.02),P＜0.001].2 年随访后帕金森病患者运动功能和认知功能较基线无显著进展,而红细胞聚集体形式的α-突触核蛋白水平较基线时特异性升高[211.66(159.71,263.73)vs 170.12(139.31,233.42),P=0.046].结论 外周红细胞α-突触核蛋白检测对于早发型帕金森病同样具有较好诊断价值,进一步证实上述指标是诊断帕金森病潜在的生物标志物.

IntroductionThe differentiation between essential tremor (ET) and Parkinson’s disease (PD) can be difficult because of the symptom overlaps. Erythrocytes are the major source of peripheral α-synuclein (α-syn), which is the most studied pathological molecular of PD. We have reported that erythrocytic α-syn levels in PD patients are significantly increased compared to those in healthy controls (HCs). However, little is known about the levels of erythrocytic α-syn species in ET patients.MethodsThis study includes 15 patients with ET, 64 patients with PD, and 49 age and sex matched HCs. A well-established electrochemiluminescence assay was used to measure the erythrocytic total and aggregated α-syn levels. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic values of erythrocytic α-syn for ET diagnosis and differentiation. The correlations of erythrocytic α-syn levels with disease durations were tested using Spearman’s Rank Correlation analysis.ResultsWe found that both erythrocytic total and aggregated α-syn concentrations are significantly increased in PD and ET patients compared to those in HCs. Erythrocytic total α-syn levels are significantly higher in ET patients than those in PD group. Furthermore, the ratios of erythrocytic aggregated to total α-syn levels in ET patients are significantly decreased than those in PD and HC subjects. We also found a significant association of erythrocytic aggregated α-syn levels with the disease duration of ET patients.ConclusionOur findings suggest new insight into the changes of erythrocytic total and aggregated α-syn levels as potential biomarkers for ET patients.

Introduction: Morphological abnormalities of erythrocytes/red blood cells (RBCs), e.g., increased acanthocytes, in Parkinson’s disease (PD) have been reported previously, although the underlying mechanisms remain to be characterized. In this study, the potential roles of α-synuclein (α-syn), a protein critically involved in PD and highly abundant in RBCs, were studied in PD patients as well as in a PD mouse model. Methods: Transgenic [PAC-Tg (SNCAA53T), A53T] mice overexpressing A53T mutant α-syn and SNCA knockout mice were employed to characterize the effect of α-syn on RBC morphology. In addition to A53T and SNCA knockout mice, the morphology of RBCs of PD patients was also examined using scanning electron microscopy. The potential roles of α-syn were further investigated in cultured RBCs and mice. Results: Morphological abnormalities of RBCs and increased accumulation of aggregated α-syn on the RBC membrane were observed in PD patients. A similar phenomenon was also observed in A53T mice. Furthermore, while mice lacking α-syn expression showed a lower proportion of acanthocytes, treating RBCs derived from SNCA knockout mice with aggregated α-syn resulted in a higher percentage of acanthocytes. In a follow-up proteomic investigation, several major classes of proteins were identified as α-syn-associated proteins on the RBC membrane, seven of which were calcium-binding proteins. Applying aggregated α-syn to the RBC membrane directly induced extracellular calcium influx along with morphological changes; both observations were adequately reversed by blocking calcium influx. Conclusions: This study demonstrated that α-syn plays a critical role in PD-associated morphological abnormalities of RBCs, at least partially via a process mediated by extracellular calcium influx.

Background Erythrocytes contain most of the peripheral α-synuclein (α-syn), which is the key pathological molecular of α-synucleinopathies including Parkinson’s disease (PD). Our objectives were to assess the efficiency of erythrocytic total and oligomeric α-syn levels as PD diagnostic biomarkers, and to identify the correlations between erythrocytic α-syn levels and physiological/psychiatrical assessment scales. Methods Home-brewed electrochemiluminescence assays were applied to assess the concentrations of erythrocytic total and oligomeric α-syn levels in a cohort including 124 patients with PD and 79 healthy controls (HCs). The correlations between erythrocytic α-syn levels and clinical measurements were assessed using Spearman’s rank test. Results Both the erythrocytic total and oligomeric α-syn levels were significantly higher in PD patients than HCs. The biomarkers adjusted for age and sex discriminated PDs from HCs well with 80% sensitivity, 89% specificity and 79% sensitivity, 83% specificity, respectively. Combining erythrocytic total and oligomeric α-syn levels by using binary logistic regression analysis with the controlling of age and sex generated a factor discriminates PDs from HCs with 88% sensitivity and 85% specificity. The erythrocytic total but not oligomeric α-syn levels adjusted for age and sex significantly correlated with anxiety scales and the MDS-UPDRS III scales in PD patients, respectively. Conclusion We showed the usefulness of erythrocytic total and oligomeric α-syn levels as biomarkers for PD. Our results also suggest the capability of erythrocytic α-syn as a potential pathological factor and therapeutic target for psychiatric symptoms in PD patients.

目的:探讨帕金森病(PD)同时伴有体位性低血压(OH)及卧位高血压(SH)患者的血流动力学、心脑血管发病率及高危因素的特征,以及对运动症状和非运动症状的影响.方法:入组PD合并OH患者198例,伴有SH 123例(SH组),不伴有SH 75例(无SH组).记录所有入组患者临床信息、实验室检查结果,进行各项运动及非运动症状临床量表的评估.进行卧立位试验及急性左旋多巴冲击试验,记录血压变化.比较2组间的基本临床信息,心脑血管疾病及风险因素,冲击试验服药前后血压的变化及量表评分.结果:伴有OH的PD患者中SH的发生率为62.1％.2组间年龄、性别、病程、左旋多巴等效剂量无明显差异.与无SH组相比,SH组同型半胱氨酸略高(P<0.05),余各项心脑血管疾病高危因素差异无统计学意义(P>0.05).SH组MDS-UPDRSⅢ运动功能总分及姿势步态异常得分更高(P<0.05);SH组在服药前卧立位试验及急性左旋多巴冲击试验后收缩压下降最大差值较高(P<0.05),但出现临床显著OH的发生率较低(P<0.05);无SH的PD-OH患者出现临床显著OH的风险是有SH的PD-OH患者的近3倍(OR=2.991,P=0.002).认知评估中,SH组的MMSE量表回忆能力子项、定向力子项、MoCA量表总分、视空间与执行功能子项、定向力子项的评分均低于无SH组(均P<0.05),但2组间认知障碍的发生率差异无统计学意义(P>0.05).结论:PD患者中合并OH及SH的发生率高,尚未发现PD-OH伴有SH增加心脑血管疾病风险,且SH对显著OH起到一定保护作用.PD-OH伴SH患者需注意跌倒和痴呆风险.

Introduction Emerging evidence has suggested that lipid metabolism is correlated with Parkinson's disease ( PD) onset and progression. However, the effect of lipid metabolism on motor performance in PD patients is still unknown. This study estimated the association between lipid profiles and the severity of motor performance in PD. Methods This cross-sectional study enrolled 279 idiopathic PD patients from the Department of Neurology of Beijing Tiantan Hospital from May 2016 to August 2018. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL- C), apolipoprotein A1 (Apo-A1), and apolipoprotein B (Apo-B) levels were detected in fast serum samples. Motor performance was assessed by Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) total scores and subscores in these patients. The associations of lipid profiles with motor performance were analyzed using multivariable linear regression models. Results Compared to males, females with PD exhibited significantly higher serum TC, LDL-C, HDL-C, Apo-A1, and Apo-B levels. When accounting for covariates, lower serum TG levels were significantly associated with higher MDS-UPDRS III total scores and gait/postural instability subscores. Additionally, the univariate linear regression model showed that in males with PD, serum HDL-C or Apo-A1 levels were significantly associated with tremor subscores. Conclusion Lower serum TG levels were associated with more severe motor performance in patients with PD and TG may be a potential predictive biomarker for motor performance in PD patients.

目的:本研究旨在探讨早发型帕金森病(EOPD)患者发生体位性低血压(OH)特征、可能的危险因素,以及OH对运动症状和非运动症状的影响.方法:入组131例EOPD患者.记录患者基本信息,进行各项运动及非运动症状临床量表的评估.测量并记录患者在急性美多巴冲击试验服药前、服药1、2、3h后卧立位血压测试,MDS-UPDRSⅢ运动症状评分,计算左旋多巴改善率.根据是否出现OH分为OH组和非OH组,比较2组的基本临床数据、各量表评分,分析OH的可能危险因素.结果:入组的131例EOPD患者纳入OH组69例,纳入无OH组62例.总OH发生率为52.7％,服药前OH发生率为25.8％,服药后为39.7％(P<0.05).OH组患者病程更长,卧位高血压、剂末现象的发生率更高,左旋多巴最大改善率更高,姿势步态异常得分更高(均P<0.05);OH组患者的冻结步态问卷(FOGQ)、Cleveland便秘评分系统(CCS)和帕金森病日常生活质量问卷调查(PDQ-39)量表评分得分更高(均P<0.05);Logistic回归分析显示卧位高血压(OR=11.057,P=0.000)和便秘(OR=1.170,P=0.019)是EOPD患者发生OH的高危因素.结论:OH是EOPD患者的常见自主神经受损表现,服用左旋多巴药物后更易发生.左旋多巴药物可使EOPD患者卧立位收缩压下降.卧位高血压和便秘是EOPD患者发生OH的高危因素.建议对PD患者进行服用抗PD药物后1～2 h的卧立位试验,明确卧位高血压及OH情况,辅助专科医生制定合适的治疗方案.

We report here for the first time that verapamil elevates cytosolic calcium. We have found that in the isolated rat osteoclast, verapamil at low micromolar concentrations did not block the elevation of cytosolic free calcium ([Ca++]i) in response to elevated extracellular calcium concentrations ([Ca++]e). However, high micromolar concentrations of verapamil (300 μM or above) led to a rapid sustained elevation of [Ca++]i. These concentrations of verapamil had effects on osteoclast morphology and resorptive activity that were similar to those produced by elevated [Ca++]e: there was a marked dose-dependent fall in cell spread area and osteoclastic bone resorption. The sensitivity of osteoclasts to high micromolar concentrations of verapamil is unique and could not be mimicked in macrophages and lymphocytes.

Purpose: Lacunae are imaging biomarkers of cerebral small vessel disease (CSVD) and are correlated with the degree of gait instability in Parkinson's disease (PD). The wearing-off phenomenon (WO) occurs more frequently in PD patients as disease progresses. The present study aimed to investigate the overall impact of the quantity and location of lacunae on the WO in PD. Patients and Methods: This retrospective, single-center study included 315 consecutive eligible patients with PD from Beijing Tiantan Hospital from May 2016 to August 2018. We collected data on demographics and clinical features, assessed lacunae and examined the presence of the WO. The association between lacunae and the WO was assessed using a binary logistic regression model. Results: The number of lacunae was significantly associated with the WO in patients with PD according to a model adjusted for age at onset, disease duration, Hoehn-Yahr (H-Y) staging, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) total score and levodopa equivalent daily dosage (LEED) (P=0.037, OR 1.156, 95% CI 1.009, 1.325) and to a model further adjusted for other CSVD imaging biomarkers (P=0.046, OR 1.172, 95% CI 1.003, 1.369). Following additional adjustment for other potential confounders, the association remained significant (P=0.043, OR 1.195, 95% CI 1.005, 1.421). Lacunae in subcortical areas (P=0.004, OR 0.498, 95% CI 0.308, 0.803) and basal ganglia (P=0.046, OR 1.616, 95% CI 1.009, 2.587), especially in the caudate nuclei (P=0.023, OR 1.104, 95% CI 0.185, 0.881), were significantly associated with the WO in PD patients. Conclusion: Our finding highlights the significant association between lacune and the WO, and lacunae may be an independent contributor to the WO in PD patients. Promoting neurovascular health may prevent the progression of the WO in PD patients.

1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, People’s Republic of China; 3Department of Neurology, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 4Department of Rehabilitation, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China Purpose: Lacunae are imaging biomarkers of cerebral small vessel disease (CSVD) and are correlated with the degree of gait instability in Parkinson’s disease (PD). The wearing-off phenomenon (WO) occurs more frequently in PD patients as disease progresses. The present study aimed to investigate the overall impact of the quantity and location of lacunae on the WO in PD. Patients and Methods: This retrospective, single-center study included 315 consecutive eligible patients with PD from Beijing Tiantan Hospital from May 2016 to August 2018. We collected data on demographics and clinical features, assessed lacunae and examined the presence of the WO. The association between lacunae and the WO was assessed using a binary logistic regression model. Results: The number of lacunae was significantly associated with the WO in patients with PD according to a model adjusted for age at onset, disease duration, Hoehn–Yahr (H-Y) staging, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) total score and levodopa equivalent daily dosage (LEED) (P=0.037, OR 1.156, 95% CI 1.009, 1.325) and to a model further adjusted for other CSVD imaging biomarkers (P=0.046, OR 1.172, 95% CI 1.003, 1.369). Following additional adjustment for other potential confounders, the association remained significant (P=0.043, OR 1.195, 95% CI 1.005, 1.421). Lacunae in subcortical areas (P=0.004, OR 0.498, 95% CI 0.308, 0.803) and basal ganglia (P=0.046, OR 1.616, 95% CI 1.009, 2.587), especially in the caudate nuclei (P=0.023, OR 1.104, 95% CI 0.185, 0.881), were significantly associated with the WO in PD patients. Conclusion: Our finding highlights the significant association between lacune and the WO, and lacunae may be an independent contributor to the WO in PD patients. Promoting neurovascular health may prevent the progression of the WO in PD patients.

INTRODUCTION:Emerging evidence has suggested that cerebral small vessel disease (CSVD) may worsen motor function and cognition in Parkinson's disease (PD). However, the effect of CSVD on anxiety and depression in patients with PD remains unknown. This study explored the multi-dimensional effects of CSVD on PD outcomes (motor, cognition, and depression/anxiety).METHODS:This cross-sectional study included 431 patients with PD from Beijing Tiantan Hospital from May 2016 to August 2019. CSVD imaging markers were assessed and the four-point CSVD burden score was calculated. Motor function (MDS-UPDRS III score and subscores), cognition (MMSE, MoCA), anxiety (HAMA), and depression (HAMD) were assessed in these patients. The associations of CSVD with these outcomes were analyzed using the Spearman's correlation and multivariable linear regression models.RESULTS:Motor dysfunction, cognitive impairment, depression, and anxiety were significantly worse in patients with severe CSVD than in those with mild CSVD. Multivariable linear regression showed that CSVD burden was significantly associated with motor dysfunction (MDS-UPDRS III score and rigidity and bradykinesia subscores), impaired cognition, and high levels of depression and anxiety. A marginally significant association was observed between CSVD burden and gait/postural instability in multivariable regression analysis. Among the CSVD imaging markers, white matter hyperintensity, number of lacunes, and microbleeds were positively correlated with the severity of motor, cognitive, and emotional impairments, while the perivascular space in the basal ganglia was only correlated with cognitive impairments.CONCLUSIONS:Comorbid CSVD may affect multiple functional domains in patients with PD. Management of cerebrovascular disease may improve PD outcomes.

INTRODUCTION:With the levodopa threshold effect for dyskinesia observed, threshold dosage of levodopa was identified in the general Parkinson's disease (PD) population. While early-onset PD (EOPD) and late-onset PD (LOPD) differ in the pathogenesis and clinical manifestations, threshold dosage of levodopa for individualized treatment remains unestablished. The objective of this study was to propose threshold dosage of levodopa in EOPD and LOPD patients, respectively.METHODS:Data on demographic and clinical and treatment measures were collected in 539 PD patients. Patients were divided into different onset groups using 50 as the cut-off age. We used univariable and multivariable analysis to screen for risk factors for dyskinesia. Receiver operating characteristic curve was used to determine the levodopa threshold dosages for dyskinesia.RESULTS:The prevalence of dyskinesia was 47.7% (53/111) in the EOPD group and 24.1% (103/428) in the LOPD group. Risk factors identified for dyskinesia include high levodopa daily dose and levodopa responsiveness for EOPD patients and high levodopa daily dose, long levodopa treatment duration, low body weight, use of entacapone, and high Hoehn-Yahr stage in off state for LOPD patients. The daily levodopa threshold dosages were 400 mg or 5.9 mg/kg for EOPD and 450 mg or 7.2 mg/kg for LOPD.CONCLUSION:EOPD patients had lower levodopa threshold dosage comparing with LOPD patients. Treatment of EOPD requires stricter levodopa dose control to delay the onset of dyskinesia.

目的 探讨交感皮肤反应(SSR)及肛门括约肌肌电图(EAS-EMG)在多系统萎缩(MSA)与帕金森病(PD)中的诊断价值.方法 对108例MSA患者(MSA组)及171例PD患者(PD组)进行SSR和EAS-EMG检查,采用ROC曲线分析两种检查的诊断价值.结果 与PD组比较,MSA组上、下肢SSR潜伏期明显延长,波幅明显下降[(1528.73±390.32)ms vs(1286.95± 180.39)ms;(2226.98±499.23)ms vs(1832.65 ±271.09)ms;(1082.44±834.41)μV vs(2626.16± 1539.60)μV;(499.01±308.18)μV vs(1734.64± 1258.92)μV,P = 0.000];MSA 组上肢潜伏期、波幅与直立性低血压(OH)明显相关,下肢潜伏期、波幅与病程、OH明显相关(P＜0.05,P＜0.01).与PD组比较,MSA组EAS-EMG平均时限、波幅、平均位相、多相波百分比、卫星电位百分比明显升高(P＜0.05,P＜0.01).SSR联合EAS-EMG检查的曲线下面积为0.92,敏感性0.73.结论 SSR联合EAS-EMG可提高对MSA与PD患者的鉴别诊断,可作为MSA患者早期自主神经功能障碍量化的诊断及鉴别诊断指标.