Search

Background: Mild cognitive impairment is one of the non-motor symptoms in Parkinson's disease (PD) and multiple system atrophy (MSA). Few studies have previously been conducted on the correlation between serum uric acid (SUA) and lipid levels and mild cognitive impairment in PD and MSA., Methods: Participants included 149 patients with PD and 99 patients with MSA. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Evaluations were conducted on SUA and lipid levels, which included triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC)., Results: Patients with PD and MSA diagnosed with mild cognitive impairment demonstrated multiple cognitive domain impairment when compared with patients with normal cognition. Attentional impairment was more pronounced in patients with MSA when compared with PD ( p = 0.001). In PD, the risk of mild cognitive impairment was lower in the highest quartiles and secondary quartile of SUA than in the lowest quartiles (odds ratio [OR] = 0.281, 95% confidence intervals [CI]: 0.097-0.810, p = 0.019; and OR = 0.317, 95% CI: 0.110-0.911, p = 0.033). In MSA, the risk of mild cognitive impairment was lower in the third and highest quartile of SUA than in the lowest quartile (OR = 0.233, 95% CI: 0.063-0.868, p = 0.030; and OR = 0.218, 95% CI: 0.058-0.816, p = 0.024). In patients with PD, the MoCA scores were negatively correlated with TC levels ( r = -0.226, p = 0.006) and positively correlated with SUA levels ( r = 0.206, p = 0.012). In MSA, the MoCA scores were positively correlated with SUA levels ( r = 0.353, p = 0.001)., Conclusions: Lower SUA levels and higher TC levels are a possible risk factor for the risk and severity of mild cognitive impairment in PD. Lower SUA levels are a possible risk factor for the risk and severity of mild cognitive impairment in MSA., (© 2024 The Author(s). Published by IMR Press.)

The aim of this trial was to investigate the safety, tolerability, and capability of serum uric acid (UA) elevation of inosine 5'-monophosphate (IMP) in multiple system atrophy (MSA). The IMPROVE-MSA trial was a randomized, double-blind, placebo-controlled trial in patients with MSA with no history of hyperuricemia-related disorders. The participants were assigned to placebo (n = 25) or IMP (n = 30) in a 1 to 1 ratio, and then followed up for 24 weeks. The primary end points included safety, tolerability, and alteration of the serum UA level during the follow-up period. The secondary end points were changes in scores of the unified MSA rating scale (UMSARS) and the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The total number of adverse events (AEs) and serious AEs was comparable between the active and placebo groups. Serum UA level (mg/dL) was significantly increased from baseline (active vs. placebo, 4.57 vs. 4.58; P = 0.98) to study end point (6.96 vs. 4.43; P < 0.001) in the active group compared with the placebo group (time × group interaction; P < 0.001). The change in UMSARS scores did not differ between the active and placebo groups. However, the active group showed better alterations in MoCA scores with nominal significance (P < 0.001) and tendency for better alterations in MMSE scores (P = 0.09) than the placebo group. Our data demonstrated that IMP treatment was generally safe and well-tolerated in patients with MSA. A further trial with a long-term follow-up is required to examine whether UA elevation will slow clinical progression in early MSA., (© 2020 The Authors. Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Objective: We aimed to investigate the association of the serum urate level with cortical thickness and white matter integrity in multiple system atrophy (MSA)., Methods: We recruited 75 MSA patients and 42 controls who underwent brain MRI and measured serum urate level at baseline. Using cortical thickness and tract-based spatial statistics analyses, we investigated the correlation between serum urate levels and cortical thickness or diffusion tensor imaging (DTI) measures in controls and MSA patients. Interaction effects were analyzed to find different patterns of correlation according to sex and clinical subtype. We evaluated the relationship between serum urate levels, DTI measures, and total UMSARS score, using path analysis., Results: Serum urate levels showed a positive correlation with FA values in the corpus callosum and a negative correlation with MD values in widespread regions including cerebellar, brainstem, and cerebral white matter in patients with MSA. Both sexes showed a negative correlation between serum urate levels and MD values without significant interaction effect. In subgroup analysis according to subtype, patients with cerebellar subtype showed a negative correlation. Serum urate levels did not correlated with cortical thickness. Path analysis showed that MD values in middle and inferior cerebellar peduncle mediated the association between serum urate level and total UMSAR score., Interpretation: The present study demonstrated that serum urate levels played a pivotal role in white matter disintegrity and clinical disability in MSA. It would provide an evidence of the role of urate as a potential neuroprotective factor against white matter neurodegeneration in MSA., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objectives: Lower serum uric acid (UA) levels are considered to be related to the risk to develop many neurodegenerative disorders. However, the association between serum UA level and multiple system atrophy (MSA) remains controversial. The aim of this meta-analysis was to evaluate the relationship between serum UA level and MSA., Patients and Methods: PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched for eligible studies. Standardized mean difference (SMD) and 95% confidence intervals (95% CI) were calculated in a fixed-effects model or a random-effects model when appropriate. Subgroup analyses were carried out based on gender. A total of 6 eligible studies involving 547 MSA patients and 637 healthy individuals were identified., Results: Meta-analysis results revealed that individuals with MSA had lower sera levels of UA as compared with healthy controls (pooled SMD is -0.51, 95%CI: -0.88 to -0.14; p = 0.006). The subgroup analysis to detect sex differences showed that the pooled SMD was -0.61 (95% CI: -0.82 to -0.40; p < 0.0001) for males and -0.22 (95% CI: -0.55 to 0.10; p = 0.18) for females compared with healthy controls., Conclusion: Our meta-analysis revealed that lower serum level of UA is associated with an increased risk of MSA and the relationship is significant in men but not in women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder that may be caused in part by oxidative stress. Uric acid (UA) protects neurons in neurodegenerative disorders via antioxidative effects. The aim of this study was to investigate the relationship between the serum UA concentration and disease progression in MSA patients., Patients and Methods: A total of 53 Japanese MSA patients were enrolled in this study. The disease progression rate was estimated by the rate of global disability scale change per year. The relationship between the serum UA concentration and disease progression was assessed by Spearman's correlation analysis. Disease progression depending on the UA concentration was also estimated by multivariate logistic regression analysis., Results: MSA patients with the highest serum UA concentration had lower disease progression rates than those with the lowest concentration. Spearman's correlation analysis showed an inverse correlation between the serum UA concentration and disease progression in male patients. Multivariate logistic regression analysis confirmed that the UA concentration was independently related to disease progression only in male patients., Conclusion: These results suggest that serum UA may be associated with disease progression in male patients with MSA., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Serum uric acid (UA) levels are reported to be decreased in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). However, clinical correlates of serum UA levels are still unclear in PD-related disorders. We conducted a cross-sectional study to evaluate the associations between serum UA levels and disease duration, disease severity, and motor function among PD, MSA, and progressive supranuclear palsy (PSP) patients., Methods: A total of 100 patients with PD, 42 patients with MSA, 30 patients with PSP, and 100 controls were included in this study. Serum UA levels were determined, and associations among serum UA levels and disease duration, disease severity, and motor function in PD, PSP, and MSA patients were evaluated., Results: Serum UA levels were significantly lower in male PD, MSA, and PSP patients compared with the controls, but not in female patients. Serum UA levels were negatively correlated with disease duration and severity in MSA and PSP patients, but no correlations were observed in PD patients. The serum UA levels were significantly decreased in the tauopathy group (PSP patients) compared with the synucleinopathy group (PD and MSA patients) after adjusting for age, gender, and body mass index., Conclusion: We found decreased serum UA levels in male patients with PD-related disorders (PD, MSA, and PSP) compared with male controls, and significant correlations between serum UA levels and disease severity in MSA and PSP patients.

Introduction: Uric acid is a natural antioxidant, and it has been shown that low levels of uric acid could be a risk factor for the development of PD. Our aim was to investigate whether uric acid plays a role in PSP., Methods: We carried out a cross-sectional study to compare serum uric acid levels between PSP patients, PD patients, and healthy controls. We also analyzed longitudinal uric acid levels in the PSP group., Results: PSP patients showed reduced levels of serum uric acid as compared to healthy controls. This reduction was similar to that found in patients with PD. Uric acid levels of PSP patients did not change with time., Conclusion: Serum uric acid levels are reduced in PSP as well as in PD compared to healthy controls. Our data suggest that high levels of uric acid could be a natural protective factor against PSP., (© 2015 International Parkinson and Movement Disorder Society.)

Background and Objective: Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA) and cognitive impairment. Uric acid has an anti-oxidative effect. Our objective is to clarify the correlations between serum uric acid and cognitive function as well as frontal lobe function in Chinese MSA patients., Methods: All of MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), and Unified MSA Rating Scale (UMSARS). The fasting serum uric acid concentrations of MSA patients were measured., Results: A total of 89 probable MSA patients with a mean age of 58.6 ± 10.0 years old and disease duration of 2.6 ± 1.5 years were included. Thirty-three patients (37.1%) had global cognitive deficits according to ACE-R. Based on FAB, 35 patients (39.3%) had frontal lobe dysfunction. After adjusting for educational years, patients with cognitive deficits had lower uric acid level than patients without cognitive deficits. Patients with frontal lobe dysfunction had lower uric acid level after adjusting for UMSARS scores. In a forward multiple linear regression, uric acid level and educational years were the variables predicting the ACE-R score (F=36.540, R(2)=0.459, p=0.0001), uric acid accounting for 14% of the total variables. Uric acid was the only variable contributing to the FAB score (F=18.551, R(2)=0.176, p=0.0001)., Conclusion: Our study suggested that low level of serum uric acid was associated with cognitive deficits in MSA. Low uric acid level predicting cognitive decline in MSA needs more studies., (Copyright © 2015. Published by Elsevier B.V.)

Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA). Uric acid has an antioxidative effect. Our aim is to clarify the correlations between serum uric acid and MSA in Chinese population. A total of 234 patients with probable MSA and 240 age- and gender- matched healthy controls were included in the study. The serum uric acid levels of all the patients and controls were evaluated. The Unified MSA Rating Scale (UMSARS) was used to assess the severity and the mean rate of annualized changes of UMSARS to assess the progression of MSA. The mean age of MSA patients was 58.90 ± 9.00 years and the mean disease duration was 2.60 ± 1.75 years. The serum uric acid levels of MSA patients were significantly lower than that of controls in males (p = 0.0001). The occurrence of MSA was increased in the lowest uric acid quartiles compared with the highest uric acid quartiles (p = 0.005). In a gender-specific analysis, increased occurrence was found in the lowest quartiles and second quartiles compared with the highest quartiles in males (p = 0.001 and p = 0.0001 respectively), but not in females. No correlation was found between the mean rate of annualized changes and serum levels of uric acid, as well as other independent factors, such as age, BMI, gender, subtype (C-type or P-type) and disease duration at the initial visit in 107 followed-up patients. MSA patients have lower levels of serum uric acid than controls. High levels of serum uric acid may be associated with a lower prevalence of MSA in the Chinese population, especially in males. However, serum uric acid does not deteriorate or ameliorate the progression of MSA.

Background: Low levels of serum urate are associated with a higher risk of Parkinson's disease (PD). Higher serum and cerebrospinal fluid (CSF) urate levels are associated with slower rates of clinical decline in PD and in multiple system atrophy (MSA)., Aims: To compare CSF and blood urate levels in healthy controls, patients with synucleinopathies and with tauopathies., Methods: We investigated urate levels in serum and CSF from 18 healthy controls, 19 patients with synucleinopathies (six patients with PD and 13 with MSA), and 24 patients with tauopathies (18 with progressive supranuclear palsy and six with corticobasal degeneration). None of the patients were treated with dopaminergic medications., Results: No significant differences were seen when comparing serum and CSF urate levels from controls across the parkinsonian diagnostic groups. However, in men, serum urate levels were significantly lower in the synucleinopathy group compared with the tauopathy group (P = 0.046), although with a broad overlap., Conclusion: Our study suggests that urate levels might provide new insights into the potential pathophysiological mechanisms underlying Parkinsonism and thereby contribute to the future management of these disorders., (© 2012 John Wiley & Sons A/S.)

Background: Recent studies have suggested that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of multiple system atrophy., Methods: We evaluated the influence of serum uric acid levels on disease progression in 52 patients with multiple system atrophy using changes in the annualized Unified Multiple System Atrophy Rating Scale scores., Results: The mean annualized Unified Multiple System Atrophy Rating Scale changes were significantly lower in patients with the highest uric acid quartile compared with those with the lowest quartile (8.4 ± 5.1 vs 20.2 ± 16.0, P = .038). Serum uric acid levels had a significant negative correlation with the annualized Unified Multiple System Atrophy Rating Scale changes (r = -0.40, P = .004). Multiple linear regression analysis showed that only serum uric acid concentration was significantly correlated with the annualized Unified Multiple System Atrophy Rating Scale changes (β = -2.687, P = .011)., Conclusions: These data suggest that serum uric acid may act as a potential disease modifier in multiple system atrophy., (Copyright © 2010 Movement Disorder Society.)