Clinical Severity Of Parkinson's Disease Research Articles

Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach

Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.

The semicircular canal function is preserved with little impact on falls in patients with mild Parkinson's disease

IntroductionPostural instability is a cardinal symptom of Parkinson's disease (PD), which suggests the vestibular system may be affected in PD. This study aimed to determine whether vestibular dysfunction is associated with the risk of falls in PD. MethodsWe prospectively recruited patients with de-novo PD at a tertiary medical center between December 2019 and March 2023. During initial assessment, each patient was queried about falls within the preceding year. All patients underwent evaluation of video head-impulse tests (video-HITs), motion analysis, mini-mental state examination (MMSE), and Montreal Cognitive Assessment (MOCA). We determined whether head impulse gain of the vestibulo-ocular reflex (VOR) was associated with clinical severity of PD or risk of falls. ResultsOverall, 133 patients (mean age ± SD = 68 ± 10, 59 men) were recruited. The median Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (MDS-UPDRS-III) was 23 (interquartile range = 16–31), and 81 patients (61 %) scored 2 or less on the Hoehn and Yahr scale. Fallers were older (p = 0.001), had longer disease duration (p = 0.001), slower gait velocity (p = 0.009), higher MDS-UPDRS-III (p < 0.001) and H&Y scale (p < 0.001), lower MMSE (p = 0.018) and MOCA scores (p = 0.001) than non-fallers. Multiple logistic regression showed that MDS-UPDRS-III had a positive association with falling (p = 0.004). Falling was not associated with VOR gain (p = 0.405). The VOR gain for each semicircular canal showed no correlation with the MDS-UPDRS-III or disease duration. ConclusionsThe semicircular canal function, as determined by video-HITs, is relatively spared and has little effect on the risk of falls in patients with mild-to-moderate PD.

Editors' Note: Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease

In “Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease,” Chen et al. reported that a reduction in fecal short-chain fatty acids (SCFAs) is associated with increased clinical severity of Parkinson disease (PD). Brenner commented that this may be attributed to the fact that a reduction in SCFAs can lead to increased growth of Escherichia coli , which produce curli fibers that can accelerate production of amyloids and subsequent action pathology related to alpha-synuclein. Lin et al. agreed that curli production may lead to alpha-synuclein aggregation and neuroinflammation, as seen in PD. The authors further concurred that the gut-brain relationship in PD may be related to SCFAs, curli-producing E. coli , functional amyloids, and alpha-synuclein. In “Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease,” Chen et al. reported that a reduction in fecal short-chain fatty acids (SCFAs) is associated with increased clinical severity of Parkinson disease (PD). Brenner commented that this may be attributed to the fact that a reduction in SCFAs can lead to increased growth of Escherichia coli , which produce curli fibers that can accelerate production of amyloids and subsequent action pathology related to alpha-synuclein. Lin et al. agreed that curli production may lead to alpha-synuclein aggregation and neuroinflammation, as seen in PD. The authors further concurred that the gut-brain relationship in PD may be related to SCFAs, curli-producing E. coli , functional amyloids, and alpha-synuclein.

Predictors of Penetration-Aspiration in Parkinson's Disease Patients With Dysphagia: A Retrospective Analysis.

Penetration-aspiration is considered the most severe sign of dysphagia, with aspiration pneumonia as one of its consequences. More than half of Parkinson's disease (PD) patients suffer from dysphagia, and aspiration pneumonia is among the primary causes of mortality in PD patients. However, the identification of predictors of penetration-aspiration in PD patients remains an understudied topic. The purpose of this study was to identify predictors of penetration-aspiration in patients with PD. The data of 89 PD patients with dysphagia who underwent routinely conducted videofluoroscopic studies of swallowing (VFSS) were included in this retrospective study. The occurrence of penetration-aspiration was defined as scores ≥3 on the Penetration-Aspiration Scale (PAS). Four commonly reported signs of dysphagia in PD patients were evaluated as possible predictors. Furthermore, the relationships between the occurrence of penetration-aspiration and liquid bolus volume as well as clinical severity of PD (modified Hoehn and Yahr scale) were examined. Logistic regression showed that a delayed initiation of the pharyngeal swallow (odds ratio [OR] = 7.47, P = .008) and a reduced hyolaryngeal excursion (OR = 5.13, P = .012) were predictors of penetration-aspiration. Moreover, there was a strong, positive correlation between increasing liquid bolus volume and penetration-aspiration (γ = 0.71, P < .001). No correlation was found between severity of PD and penetration-aspiration (γ = 0.077, P = .783). Results of the present study allow for a better understanding of penetration-aspiration risk in PD patients. They are useful for treatment planning in order to improve safe oral intake and adequate nutrition.

Everyday functioning in Parkinson's disease: Evidence from the Revised-Observed Tasks of Daily Living (OTDL-R)

IntroductionPerformance tasks are presumed to have greater validity than rating scales in assessing day-to-day behaviors in Parkinson's disease (PD). One such task is the revised Observed Tasks of Daily Living (OTDL-R), which has been used extensively in healthy older adults, and but not yet empirically examined in PD. Thus, the aims of the current study were to examine and determine the impact of cognitive, motor, and mood symptoms on OTDL-R performance in PD. MethodNineteen non-demented PD patients and 18 healthy older adults (HC) were administered measures of mood and cognitive functioning, and the OTDL-R (subtests include medication and telephone use, and medication management). Clinical severity of PD was assessed using the H&Y stage, UPDRS, and Schwab and England functional disability scores. ResultsMann Whitney U tests indicated the PD patients were significantly slower to complete the OTDL-R and performed worse on only the telephone use subtest, relative to the HC group. In the PD group, hierarchical regression analyses revealed memory, attention, and initiative/perseveration were uniquely associated with the financial management subtest, after controlling for motor severity (ps < .05). No other significant relationships were found. ConclusionsPD patients were slower to complete the OTDL-R, but only less accurate on the telephone use subtest. Poor performance on the telephone use subtest may be related to motor severity, while poor performance on the financial management subtest was related to attention and working memory. Overall, the findings warrant future investigation to determine the validity and reliability of the OTDL-R in PD.

The effect of REM sleep behaviour disorder on clinical severity in Parkinson's disease

Differently from previous studies that directly compared Parkinson's disease (PD) patients with and without rapid eye movement (REM) sleep behavioural disorder (RBD) for the stage, severity, and duration of disease, this study investigated the relationship between the duration and clinical severity of disease in PD patients with and without RBD. Materials and methods: This retrospective study consisted of 141 PD patients older than 18 years of age. The clinical diagnosis of RBD was based on the minimal diagnostic criteria of the revised 2001 International Classification of Sleep Disorders. The patients were divided into 2 subgroups, those with and without clinical RBD. The groups were then compared with each other for sex, age, the duration of disease, and the Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale scores. The correlation between the duration of disease and the clinical severity of PD was analysed in all patients. Results: There was no significant difference between the groups in terms of sex, age, disease duration, and clinical severity scores. For the RBD patients there was a weak positive correlation between the duration of PD and clinical severity scores. However, there was no such correlation in the non-RBD (NRBD) subgroup. Conclusion: Our study indicates that in PD patients with RBD compared with NRBD patients, the time taken to reach the same clinical severity scores may be shorter.

In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with 18F-AV-133

PET provides a noninvasive means to evaluate the functional integrity of the presynaptic monoaminergic system in the living human brain. In this study, a novel (18)F-labeled tetrabenazine derivative, (18)F-(+)fluoropropyldihydrotetrabenazine ((18)F-AV-133), was used for the noninvasive assessment of the vesicular monoamine transporters type 2 (VMAT2) in 17 Parkinson disease (PD) patients and 6 healthy controls. The binding potential (BP) of (18)F-AV-133 was calculated using Logan graphical analysis. Voxel-based and volume-of-interest-based analyses of BP images were performed to examine brain regional reductions in VMAT2 density in PD. VMAT2 BP was decreased by 81% in the posterior putamen, 70% in the anterior putamen, and 48% in the caudate nucleus of PD patients. Voxel-based analysis demonstrated VMAT2 reductions in the striatum and mid brain of PD patients. Furthermore, VMAT2 BPs in the caudate nuclei significantly correlated with the clinical severity of PD. These findings indicate that the novel (18)F-labeled ligand (18)F-AV-133 can sensitively detect monoaminergic terminal reductions in PD patients. Studies with (18)F-AV-133 may allow the presymptomatic identification of individuals with disorders characterized by degeneration of dopaminergic nigrostriatal afferents.

Secretion of DJ-1 into the serum of patients with Parkinson's disease

DJ-1 was initially identified by us as a novel oncogene and has later been found to be a causative gene for familial Parkinson's disease PARK7. DJ-1 plays role in transcriptional regulation and in oxidative stress function, and loss of its function is thought to be related to onset age, mode of progression and clinical severity of both familial and sporadic forms of Parkinson's disease (PD). DJ-1 is localized both in the cytoplasm and nucleus, and it has been reported to be secreted into the serum or plasma of patients with breast cancer, melanoma, familial amyloidotic polyneuropathy and stroke. In this study, levels of DJ-1 secreted into the serum of healthy controls and patients with sporadic PD were examined by using a DJ-1 ELISA kit, and the level of oxidative stress in the serum was also measured. The results showed that DJ-1 was secreted into the serum of both healthy controls and PD patients. There was no significant difference between the levels of secreted DJ-1 in two groups, and correlations of levels of secreted DJ-1 with age, clinical severity of PD and level of oxidative stress were not found.