Parkinson's Disease Patients Research Articles

TMEM16F regulates pathologic α-synuclein secretion and spread in cellular and mouse models of Parkinson's disease.

One of the main hallmarks of Parkinson's disease (PD) pathology is the spread of the aggregate-prone protein α-synuclein (α-syn), which can be detected in the plasma and cerebrospinal fluid of patients as well as in the extracellular environment of neuronal cells. The secreted α-syn can exhibit "prion-like" behavior and transmission to naïve cells can promote conformational changes and pathology. The precise role of plasma membrane proteins in the pathologic process of α-syn is yet to be fully resolved. The TMEM16 family of lipid scramblases and ion channels has been recently associated with cancer and infectious diseases but is less known for its role in aging-related diseases. To elucidate the role of TMEM16F in α-syn spread, we transduced neurons derived from TMEM16F knockout mice with a reporter system that enables the distinction between donor and recipient neurons of pathologic α-synA53T. We found that the spread of α-synA53T was reduced in neurons derived from TMEM16F-knockout mice. These findings were recapitulated invivo in a mouse model of PD, where attenuated α-synA53T spread was observed when TMEM16F was ablated. Moreover, we identified a single nucleotide polymorphism in TMEM16F of Ashkenazi Jewish PD patients resulting in a missense Ala703Ser mutation with enhanced lipid scramblase activity. This mutation is associated with altered regulation of α-synA53T extracellular secretion in cellular models of PD. Our study highlights TMEM16F as a novel regulator of α-syn spread and as a potential therapeutic target in synucleinopathies.

LRRK2 Inhibitors as Promising Treatment for Parkinson's Disease.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, with current treatments offering only temporary symptomatic relief. There is an urgent need for the development of novel therapeutic approaches. Abnormal increases in LRRK2 kinase activity have been identified in both sporadic and familial PD patients, suggesting that inhibiting LRRK2 kinase activity presents a promising avenue for the pursuit of effective PD treatment strategies. In this Viewpoint, we discuss the exciting new insights regarding the development of LRRK2 kinase inhibitors as a treatment for Parkinson's disease.

The effectiveness and safety of botulinum toxin injections for managing motor disorders of patients with Parkinson's disease: A meta-analysis of randomized controlled trials.

This study aimed to assess the effectiveness and safety of botulinum toxin (BTX) injections for managing motor disorders in patients with Parkinson's disease (PD). An electronic search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from available randomized controlled trials (RCTs) assessing BTX injections for motor disorders in PD patients were extracted for meta-analysis. Ultimately, 215 patients from eight RCTs were enrolled. Pooled analyses indicated that BTX was more effective than placebo in improving tremor (standardized mean difference [SMD] = 0.96, 95% CI [0.34, 1.58], p < 0.01), whereas no notable differences were observed between BTX and placebo regarding freezing of gait (SMD = 0.66, 95% CI [-0.26, 1.58], p = 0.162), United Parkinson's Disease Rate Scale (UPDRS) III score (SMD = -0.20, 95% CI [-1.17, 0.76], p = 0.68) and clinical global impression (CGI) score (SMD = 0.84, 95% CI [-0.74, 2.42], p = 0.298). Adverse events related to BTX injections were comparable to placebo (OR = 1.74, 95% CI [0.59, 5.14], p = 0.32). The current evidence suggests that BTX is effective and safe in treating PD tremor but fails to provide therapeutic benefits for freezing of gait and motor functional scores in PD patients. Furthermore, the limited number of included studies and heterogeneity in BTX intervention protocols suggest more research is needed, with additional standardized RCTs, to better understand and optimize BTX injections for motor disorders in PD.

Blood-Based Nanoparticle-Enhanced Quaking-Induced Conversion (Nano-QuIC): Inhibitor-Resistant Detection of Seeding Activity in Patients Diagnosed with Parkinson's Disease.

A hallmark of α-synucleinopathies (e.g., Parkinson's disease) is the misfolding and aggregation of α-synuclein in tissues and biological fluids. Protein amplification assays like real-time quaking-induced conversion (RT-QuIC) are sensitive yet currently limited to semi-invasive sample types such as cerebrospinal fluid because more accessible samples, such as blood, contain inhibitors. Here, we show that Nanoparticle-enhanced Quaking-induced Conversion (Nano-QuIC) can double the speed of reactions spiked with misfolded α-synuclein while increasing sensitivity 100-fold in human plasma. Nano-QuIC detected spike concentrations down to 90 pg/mL in lysed whole blood, while reactions without nanoparticles (RT-QuIC) failed to have any detection due to the presence of strong inhibitors. Moreover, Nano-QuIC showed increased seeding activity in plasma samples from Parkinson's patients (n = 4) versus healthy controls (n = 4). This sets the groundwork for the noninvasive diagnostic use of Nano-QuIC, potentially enabling early disease detection and management through blood-based testing.

High correlation of quantitative susceptibility mapping and echo intensity measurements of nigral iron overload in Parkinson's disease.

Quantitative susceptibility mapping (QSM) and transcranial sonography (TCS) offer proximal evaluations of iron load in the substantia nigra. Our prospective study aimed to investigate the relationship between QSM and TCS measurements of nigral iron content in patients with Parkinson's disease (PD). In secondary analyses, we wanted to explore the correlation of substantia nigra imaging data with clinical and laboratory findings. Eighteen magnetic resonance imaging and TCS examinations were performed in 15 PD patients at various disease stages. Susceptibility measures of substantia nigra were calculated from referenced QSM maps. Echogenicity of substantia nigra on TCS was measured planimetrically (echogenic area) and by digitized analysis (echo-intensity). Iron-related blood serum parameters were measured. Clinical assessments included the Unified PD Rating Scale and non-motor symptom scales. Substantia nigra susceptibility correlated with echogenic area (Pearson correlation, r = 0.53, p = 0.001) and echo-intensity (r = 0.78, p < 0.001). Individual asymmetry indices correlated between susceptibility and echogenic area measurements (r = 0.50, p = 0.042) and, more clearly, between susceptibility and echo-intensity measurements (r = 0.85, p < 0.001). Substantia nigra susceptibility (individual mean of bilateral measurements) correlated with serum transferrin saturation (Spearman test, r = 0.78, p < 0.001) and, by trend, with serum iron (r = 0.69, p = 0.004). Nigral echogenicity was not clearly related to serum values associated with iron metabolism. Susceptibility and echogenicity measurements were unrelated to PD duration, motor subtype, and severity of motor and non-motor symptoms. The present results support the assumption that iron accumulation is involved in the increase of nigral echogenicity in PD. Nigral echo-intensity probably reflects ferritin-bound iron, e.g. stored in microglia.

Diagnostic Potential of NEAT1, hsa-let-7a-5p, and miR-506-3p in Early-stage Parkinson's Disease.

Parkinson's disease (PD) is a multifaceted disease that is influenced by both genetic and environmental parameters. Non-coding RNAs have been shown to be ideal biomarkers for several diseases, including PD. This study was conducted to evaluate the expression levels of NEAT1, hsa-let-7a-5p, and miR-506-3p in individuals with PD to assess their efficacy for early-stage PD diagnosis. Twenty-four patients with PD and 29 healthy individuals participated in this study. The IntaRNA tool was used to predict potential base pairings between NEAT1 and let-7a-5p, and NEAT1 and miR-506-3p. RT-qPCR was employed to measure the relative expression of tyrosine hydroxylase (TH), as well as nuclear enriched abundant transcript 1 (NEAT1), hsa-let-7a-5p, and miR-506-3p levels in both groups. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic value. The PD group exhibited significantly elevated NEAT1 expression levels compared to the healthy control group. While the PD group exhibited an insignificant decreased TH expression level relative to the healthy group. Furthermore, the levels of hsa-let-7a-5p and miR-506-3p expression were seen to be decreased in patients with PD in comparison to the control group. Integration of NEAT1, hsa-let-7a-5p, and miR-506-3p levels significantly enhanced diagnostic capabilities and increased the AUC to 0.9501 (95% confidence interval: 0.8978-1.000, p < .0001). The elevated NEAT1 expression and the decreased expression of hsalet- 7a-5p and miR-506-3p in PD patients indicate that these factors might contribute to the disease's pathogenesis. Combining the ROC curves of NEAT1 and hsa-let-7a-5p with miR-506-3p showed improved sensitivity and specificity, facilitating more accurate PD diagnosis. More importantly, they may contribute as promising non-invasive biomarkers for PD diagnosis.

Dopamine transporter availability based on white matter hyperintensity during early to mid-stage Parkinson's disease and multiple system atrophy: a case control study.

To evaluate the association of white matter hyperintensity (WMH) with dopamine transporter (DAT) availability in patients with early to mid-stage parkinson's disease (PD) and multiple system atrophy (MSA). The clinical and imaging data of 55 patients were collected, including 38 PD and 17 MSA patients and the clinical features of the two groups were compared. DAT specific binding ratio (SBR) were compared between severe and non-severe WMH groups, and between PD and MSA groups. The relationships of WMH with DAT availability and basic clinical characteristics were analyzed. Multiple linear regression analysis showed that age was the only significant variable showing correlation WMH. Age was the only clinical variable significantly correlated with WMH in PD patients (coefficient for periventricular white matter hyperintensity: 0.430, P = 0.007; coefficient for deep white matter hyperintensity: 0.381, P = 0.018). There was no significant correlation between WMH and SBRs and age in MSA patients. The SBR of the caudate nucleus and anterior putamen was significantly lower in the severe WMH group of patients than in the non-severe WMH group (P < 0.05). The values of the caudate nucleus, anterior putamen, and anterior putamen/posterior putamen were significantly lower in PD patients with than without severe WMH (P < 0.05), and the damage to the striatal DAT in MSA patients with severe WMH was similar to the non-severe patients (P>0.05). Patients with PD and a high WMH score had lower DAT availability. WMH affected the availability of DAT in patients with early to mid-stage PD compared to MSA.

Prevalence and Clinical Significance of Skin Manifestations in Parkinson Disease Patients

Background: Parkinson's disease (PD) is primarily characterized by motor symptoms, but non-motor symptoms, including skin manifestations, are increasingly recognized. These remain underexplored despite their potential impact on quality of life. Objectives: This study aimed to evaluate the prevalence and clinical features of skin findings in PD patients, with a focus on identifying potential pathogenetic links between dermatological conditions and PD. Methods: A total of 215 PD patients were included. Comprehensive dermatological examinations were performed, and demographic and clinical data were collected. Statistical analysis was conducted using SPSS 23.0, with significance set at P &lt; 0.05. Results: Skin conditions were found in 92.1% of PD patients. Xerosis, seborrheic dermatitis, and hyperhidrosis were the most common findings. Pre-PD xerosis was associated with an earlier stage of PD (P = 0.001). Use of PD medications, such as levodopa/carbidopa/entacapone, was linked to a lower incidence of seborrheic dermatitis (P = 0.040). A significant correlation was also noted between rosacea and cherry angioma (P = 0.01). Conclusion: Dermatological conditions are prevalent in PD and may precede its motor symptoms. Skin assessments could aid early diagnosis and management of PD, highlighting the need for further research on their pathogenetic mechanisms.

Directional Subthalamic Deep Brain Stimulation Better Improves Gait and Balance Disorders in Parkinson's Disease Patients: A Randomized Controlled Study.

To investigate the effects of directional subthalamic deep brain stimulation (STN-dDBS) on gait and balance disorders, including freezing of gait (FOG), in patients with advanced Parkinson's disease (PD). We included 10 participants who underwent STN-DBS and presented severe preoperative FOG, in a randomized, double-blind, crossover study. We used segmented DBS electrodes to investigate whether directing the predicted volume of tissue activated (VTA) to overlap the central STN preferentially improved gait and balance disorders compared to directional DBS applied in the more posterior STN (sensorimotor). We also assessed non-directional (ring-mode) STN-DBS. Our primary outcome was gait and balance control measured using instrumented gait recordings. Each patient had a pre-operative structural and diffusion-weighted imaging to model individual VTAs and to examine cortico-subthalamic connectivity. We used linear mixed-effects models to contrast the effects of central STN-dDBS, posterior STN-dDBS, and ring-mode STN-DBS. Central STN-dDBS produced significantly better improvement in gait and balance control compared to posterior STN-dDBS (p = 0.027), with fewer FOG episodes (p < 0.001). Conversely, ring-mode STN-DBS resulted in worsened postural control compared to central STN-dDBS (p = 0.009). The cortico-subthalamic connectivity with the STN VTAs involved mostly primary sensorimotor, premotor, and medial frontal cortices, with a higher overall cortico-STN connectivity with ring-mode STN-DBS. Central STN-dDBS represents the best option to improve gait and balance disorders in PD patients, including FOG. Our findings raise the possibility of reprogramming STN-DBS toward the central area in selected patients with disabling FOG and/or postural instability after surgery. ANN NEUROL 2024.

P1 evoked by facial expression images is enhanced in Parkinson’s disease patients with depressive symptoms

IntroductionDepressive symptoms are most common non-motor symptoms in Parkinson’s disease (PD), which is often overlooked due to absence of rapid and objective diagnostic biomarkers. Electroencephalography (EEG)-based event-related potentials (ERPs) is commonly used to assess emotional processes. The aim of this study was to investigate changes in ERPs in PD patients exhibiting depressive symptoms and to provide a reliable biomarker for assisting in the diagnosis of PD with depressive symptoms.MethodsWe conducted a case–control study involving 30 PD patients with (dPD group) or without depressive symptoms (nPD group) and 13 age matched healthy controls (HC). We recorded EEG of the patients during the emotional picture stimulation task and analyzed the difference in the early ERPs potentials (P1, N170, early posterior negativity) and their correlation with the severity of symptoms in PD patients.ResultsOur results found that P1 amplitude in the occipital region of the dPD group in response to emotional faces was significantly higher than that of nPD and HC group, and it was positively correlated with severity of depressive symptoms in PD patients.ConclusionOur study shows that facial expression-induced enhancement of P1 amplitude can be utilized as a rapid and objective indicator to screen for depressive symptoms in PD.

α-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice

Pathological forms of α-synuclein contribute to synucleinopathies, including Parkinson’s disease (PD). Most cases of PD arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms in animal models. We quantitatively profiled nearly 630 metabolites in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice, compared to wild-type (WT) animals, and comparing germ-free (GF) to specific pathogen-free (SPF) animals (n = 5 WT-SPF; n = 6 ASO-SPF; n = 6 WT-GF; n = 6 ASO-GF). Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. The microbial metabolite trimethylamine N-oxide (TMAO) strongly correlates from the gut to the plasma to the brain in mice, notable since TMAO is elevated in the blood and cerebrospinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and microbiome in a mouse model of PD.

Multimodal MRI changes associated with non-motor symptoms of rapid eye movement sleep behaviour disorder in Parkinson's disease patients.

Parkinson's disease (PD), a prevalent neurodegenerative disorder, assumes a more adverse prognosis when accompanied by rapid eye movement sleep disorder (RBD). Non-motor symptoms, particularly sleep and emotional disturbances, significantly impair patients' quality of life. This study aimed to investigate the neuroimaging underpinnings of PD-RBD using structural and functional magnetic resonance imaging (MRI) and to explore the associations between these imaging biomarkers and non-motor symptoms. Brain scans were acquired from 33 PD patients without and 21 with probable RBD (PD-pRBD). Comparative analyses were performed to evaluate structural and functional alterations between the two groups. Additionally, the correlations between neuroimaging metrics and clinical assessment scales were assessed. PD-pRBD patients demonstrated more pronounced grey matter atrophy, particularly in the putamen and insula. Functional MRI revealed decreased amplitude of low-frequency fluctuations (ALFF) in the bilateral posterior cingulate cortex and left precuneus of PD-pRBD patients. Furthermore, reduced functional connectivity (FC) was observed in specific regions of the whole brain and within the default mode network (DMN) in PD-pRBD. Notably, a negative correlation was found between mean ALFF values in the left posterior cingulate cortex of PD-pRBD patients and Hamilton Depression Rating Scale scores. PD-pRBD is characterized by more severe grey matter loss and functional MRI abnormalities compared to PD alone. Dysfunction of the posterior cingulate cortex is implicated in more pronounced affective impairments, providing novel insights into the complex pathophysiology of PD-RBD.

Measurement of α-synuclein as protein cargo in plasma extracellular vesicles

Extracellular vesicles (EVs) are released by all cells and hold great promise as a class of biomarkers. This promise has led to increased interest in measuring EV proteins from both total EVs as well as brain-derived EVs in plasma. However, measuring cargo proteins in EVs has been challenging because EVs are present at low levels, and EV isolation methods are imperfect at separating EVs from free proteins. Thus, knowing whether a protein measured after EV isolation is truly inside EVs is difficult. In this study, we developed methods to measure whether a protein is inside EVs and quantify the ratio of a protein in EVs relative to total plasma. To achieve this, we combined a high-yield size-exclusion chromatography protocol with an optimized protease protection assay and Single Molecule Array (Simoa) digital enzyme-linked immunoassays (ELISAs) for ultrasensitive measurement of proteins inside EVs. We applied these methods to analyze α-synuclein and confirmed that a small fraction of the total plasma α-synuclein is inside EVs. Additionally, we developed a highly sensitive Simoa assay for phosphorylated α-synuclein (phosphorylated at the Ser129 residue). We found enrichment in the phosphorylated α-synuclein to total α-synuclein ratio inside EVs relative to outside EVs. Finally, we applied the methods we developed to measure total and phosphorylated α-synuclein inside EVs from Parkinson's disease and Lewy body dementia patient samples. This work provides a framework for determining the levels of proteins in EVs and represents an important step in the development of EV diagnostics for diseases of the brain, as well as other organs.

MicroRNA-Targeted Gene Regulation in Salivary Gland Tissue of De Novo Parkinson's Disease Patients.

Although α-synucleinopathy has been confirmed in the submandibular gland (SMG) tissue of Parkinson's disease (PD) patients, in-depth disease-related molecular research, such as tissue-specific transcriptional signals, has not been performed. In the present study, disease-relevant tissue-specific transcriptional signals in SMG tissue from PD patients were investigated to identify potential diagnostic, prognostic, and pathophysiologic biomarkers. Here, seven de novo drug-naïve PD patients and six age- and sex-matched individuals without neurological or psychological diseases were enrolled. Total RNA sequencing (RNA-seq) and total small RNA-seq (smRNA-seq) were performed on SMG tissue and blood samples, with 26 RNA-seq and 26 smRNA-seq samples used for the final analysis. Differentially expressed genes (DEGs) and microRNAs in SMG tissue and blood from PD patients were obtained and their functional integration and interaction network were analyzed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs interacted with cytokine-, inflammation-, and immune-related pathways. Synphilin-1 expression was significantly downregulated in SMG tissue of PD patients, and α-synuclein expression did not significantly differ between PD patients and controls in either SMG tissue or blood. Fifteen tissue-specific miRNA signals in SMG tissue were identified that showed better diagnostic ability compared with those in blood samples. The correlation between DEGs and environmental factors appeared altered in PD patients. The results indicated the DEGs and microRNA signatures identified in SMG tissue may be promising diagnostic and prognostic biomarkers. These molecular insights offer potential avenues for the development of novel therapeutic strategies targeting the underlying disease mechanisms in PD patients.

Association between serum IGF‑1 levels and non-motor symptoms in Parkinson's disease.

We aimed to measure serum insulin-like growth factor 1 (IGF-1) levels in Parkinson's disease (PD) patients and assess their correlation with non-motor symptoms (NMS). Emerging evidence suggests that abnormal levels of IGF-1 play a crucial role in the development of PD. Further systematic research is needed to explore the potential roles of abnormal IGF-1 levels in NMS of PD. The study enrolled a total of 129 PD patients and 130 healthy controls (HCs). Within the PD cohort, 74 patients were classified as being in the early stage, while 55 were in the moderate stage. This study found no significant difference in serum IGF-1 levels between PD patients and HC. Further analysis revealed no significant difference in IGF-1 levels between early-stage PD and those in the moderate stages. Linear regression analysis indicated a significant association between serum IGF-1 levels and Nonmotor Symptom Scale (NMSS) scores in PD patients. Linear regression analysis revealed significant correlations between serum IGF-1 levels and general cognitive function, information processing speed, and executive function in PD patients. Furthermore, lower serum IGF-1 levels were associated with fatigue in PD patients. In summary, our study suggests a potential association between serum IGF-1 levels and specific NMS in patients with PD. These findings highlight the importance of long-term follow-up studies to determine whether serum biomarkers can serve as valuable tools for early detection of NMS in PD.

Serum alpha klotho levels in Parkinson's Disease.

Parkinson's Disease (PD), a neurodegenerative disorder, is associated with substantial morbidity. α-Klotho, an anti-aging protein known for its neuroprotective properties, has gained attention. This study aims to assess serum levels of α-Klotho in PD patients. This study is a cross-sectional case-control study. PD was diagnosed according to UK Parkinson Disease Society Brain Bank criteria. Serum α-Klotho level was measured using a commercially available enzyme-linked immunosorbent assay. Of the 314 participants in the study, 157 were patients with PD and 157 were controls. Lower levels of α-Klotho were observed in PD (0.85 nmol/L) in comparison to the controls (1.47 nmol/L, p < 0.001). α-Klotho levels were also significantly lower among PD patients with dementia compared to PD patients without dementia. In logistic regression analysis, α-Klotho (OR: 0.04, p < 0.001) demonstrated a significant relationship between PD. A significant correlation was identified between α-Klotho levels and Mini-Mental State Examination scores in PD patients. The sensitivity and the specifity of α-Klotho were 90% and 65% for predicting PD. Our findings suggest that α-klotho could potentially serve as a biomarker. However additional studies are needed to confirm our findings.

Complement Receptor 1 Is a Potential Extracerebral Factor Promoting α-Synuclein Pathology.

The deposition of pathological α-synuclein (α-Syn) in the central nervous system (CNS) is a hallmark of Parkinson's disease (PD). Notably, pathological α-Syn exists not only in the CNS but also in peripheral organs and body fluids in PD patients. Emerging evidence has shown the transmission of α-Syn pathology from the body to the brain. Nevertheless, the factors that drive the aggregation of peripheral α-Syn remain largely unknown. Here, we revealed that complement receptor 1 (CR1), a component of the peripheral blood system, acts as a promoter of α-Syn pathology. The transmembrane domain of CR1 (CR1-TM) exacerbates α-Syn phosphorylation and aggregation in vitro. Furthermore, intravenous injection of α-Syn fibrils induced the formation of α-Syn pathology in the brain. Co-administration of CR1-TM exacerbated α-Syn pathology induced by intravenous injection of preformed α-Syn fibrils. Our findings suggest that extracerebral factors such as CR1 can drive α-Syn pathology and serve as therapeutic targets for treating synucleinopathies.

Increased dementia risk in patients with Parkinson's disease attributed to metabolic syndrome.

Metabolic syndrome (MetS) manifests resembling pathophysiological mechanisms with Parkinson's disease (PD). Current research on the overall population has emphasized MetS as a freestanding risk factor for cognition. This research aims to explore the impact of MetS on cognition in Parkinson's patients. We involved subjects identified as having early-stage PD patients. The MetS was diagnosed dependent on parameters overviewed in the National Cholesterol Education Program's Adult Treatment Panel III. The clinical severity and stages in patients with PD were dependent on the disease rating scales. The cognition was evaluated by the Turkısh version of the Montreal Cognitive Assessment Scale (MoCA-TR). The cases were categorized according to cognitive failure: mild cognitive impairment in PD (PD-MCI), and PD dementia (PDD). Metabolic syndrome was present in 39.6% of the participants. 22.0% of patients were in the normal cognition, 29.1% in the PD-MCI group, and 48.9% in the PD-D group. The cognitive scores in patients with MetS is considerably lower than MetS negative group. A statistically notable inverse association was detected between fasting blood glucose levels and the visual-spatial/executive functions, naming, language, and orientation scores. The multivariate logistic regression analysis showed individuals with MetS were found to have an 11.308 times higher risk of PD-D (odds ratio [OR]: 11,3, 95% confidence interval [CI]: 1.61-79.2 ). We discerned the occurrence of MetS in PD raises the possibility of advancing dementia. This suggests that considering MetS in this patient group could contribute to the effective management of dementia.

Effectiveness and safety of levodopa-entacapone-carbidopa infusion in Parkinson disease: A real-world data study.

Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed device-aided therapy for advanced Parkinson disease (PD) patients. The aim of this study was to report real-world evidence about the effectiveness, tolerability, and safety of LECIG in PD patients. A multicenter observational retrospective study of the first patients who initiated LECIG in Spain was performed. All neurologists with an experience of at least two patients treated until 30 March 2024 were invited to participate. Data about effectiveness and safety from the medical records (V0, pre-LECIG; V1, initiation of LECIG; V2, post-LECIG follow-up) with a total of 246 variables were collected. Seventy-three PD patients (61.6% males, 70.1 ± 9.1 years old) from 21 Spanish centers with a mean disease duration of 14.4 ± 6.3 years (range = 5-31) were included. Twenty-six patients (35.6%) were switched directly from levodopa-carbidopa intestinal gel. The mean exposure to LECIG was 177.3 ± 110.5 days (range = 7-476). The mean daily OFF time decreased from 5.2 ± 3 (pre-LECIG) to 1.9 ± 1.8 (post-LECIG; n = 66, p < 0.0001). Global improvement was observed in >85% of the patients. No significant change was detected in the levodopa equivalent daily dose from V0 to V2. Only 7% received 24-h infusion, and 24.7% required more than one cartridge per day at V2. Thirty-four patients (46.6%) had at least one adverse event related to LECIG and/or the device system. Five patients (6.8%) discontinued LECIG. LECIG was safe and effective in advanced PD patients.

Peripheral biomarkers of Parkinson’s disease and its correlation with clinical symptoms: a case-control study

BackgroundInflammation significantly impacts Parkinson’s disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive.ObjectiveTo identify the peripheral biomarkers of PD and its correlation with the motor and non-motor symptoms of PD.Methods79 PD patients and 65 controls were included in this study. Clinical information and the serum levels of IL-8, IL-27, IL-33, β-NGF, AgRP, and TRAILR2 in the participants were collected. Appropriate scales were used to assess the symptoms of PD. For the factors with significant differences in the two groups, multivariable logistic regression was used to determine its relationship with PD. Moreover, spearman correlation was conducted to explore the correlation between the factors and PD related symptoms. The IL-27 level was compared between the cognitively healthy PD group and the mild cognitive impairment in PD (PD-MCI). The serum level of TRAILR2 was positively correlated with age and was not associated with other clinical characteristics related to PD.ResultsCompared to controls, the serum levels of IL-27(P = 0.013) were increased whereas the levels of TRAILR2(P = 0.008) were decreased in PD patients. IL-8, IL-33, β-NGF, and AgRP showed no significant differences between the two groups. After controlling for the other variables, IL-27 was considered as an independent risk factor for PD in the multivariable logistic regression model. The receiver operating characteristic (ROC) curve for diagnosing PD with IL-27 yielded an area under the curve (AUC) of 0.621. Additionally, IL-27 level in PD patients was positively correlated with age, the disease duration, LEDD and negatively correlated with the MoCA scores. However, no significant difference was found in IL-27 levels between cognitively healthy PD and PD-MCI groups.ConclusionElevated serum IL-27 was a risk factor for PD and positively correlated with the cognitive decline in PD.