Parkinson's Disease最新文献

Insulin desensitization has been observed in the brains of patients with Parkinson's disease (PD), which is a progressive neurodegenerative disorder for which there is no cure. Semaglutide is a novel long-actingglucagon-likepeptide-1 (GLP-1) receptor agonist that is on the market as a treatment for type 2 diabetes. It is in a phase II clinical trial in patients with PD. Two previous phase II trials in PD patients showed good effects with the older GLP-1 receptor agonists, exendin-4 and liraglutide. We have developed a dual GLP-1/GIP receptor agonist (DA5-CH) that can cross the blood-brain barrier (BBB) at a higher rate than semaglutide. We tested semaglutide and DA5-CH in the 6-OHDA-lesion rat model of PD. Treatment was semaglutide or DA5-CH (25 nmol/kg, i.p.) daily for 30 days postlesion. Both drugs reduced the apomorphine-induced rotational behavior and alleviated dopamine depletion and the inflammation response in the lesioned striatum as shown in reduced IL-1β and TNF-α levels, with DA5-CH being more effective. In addition, both drugs protected dopaminergic neurons and increased TH expression in the substantia nigra. Furthermore, the level of monomer and aggregated α-synuclein was reduced by the drugs, and insulin resistance as shown in reduced pIRS-1^ser312 phosphorylation was also attenuated after drug treatment, with DA5-CH being more effective. Therefore, while semaglutide showed good effects in this PD model, DA5-CH was superior and may be a better therapeutic drug for neurodegenerative disorders such as PD than GLP-1 receptor agonists that do not easily cross the BBB.

The hemiparkinsonian nonhuman primate model induced by unilateral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the carotid artery is used to study Parkinson's disease. However, there have been no studies that the contralateral distribution of MPTP via the cerebral collateral circulation is provided by both the circle of Willis (CoW) and connections of the carotid artery. To investigate whether MPTP-induced unilaterally damaged regions were determined by asymmetrical cerebral blood flow, the differential asymmetric damage of striatal subregions, and examined structural asymmetries in a circle of Willis, and blood flow velocity of the common carotid artery were observed in three monkeys that were infused with MPTP through the left internal carotid artery. Lower flow velocity in the ipsilateral common carotid artery and a higher ratio of ipsilateral middle cerebral artery diameter to anterior cerebral artery diameter resulted in unilateral damage. Additionally, the unilateral damaged monkey observed the apomorphine-induced contralateral rotation behavior and the temporary increase of plasma RANTES. Contrastively, higher flow velocity in the ipsilateral common carotid artery was observed in the bilateral damaged monkey. It is suggested that asymmetry of blood flow velocity and structural asymmetry of the circle of Willis should be taken into consideration when establishing more efficient hemiparkinsonian nonhuman primate models.

Background: Gait and balance disorders in patients with idiopathic Parkinson's disease (PD) lead to major mobility limitations. To counteract this, physical therapy such as gait, balance, or resistance training is applied. Integrative training methods, which combine these elements, could be particularly effective.

Objective: The objective of this study is to evaluate and compare the effects of two integrative interventions on gait and balance of patients with PD.

Methods: Twenty-six patients with PD received either resistance training in combination with gait training (gait resistance training, GRT) or resistance training in combination with balance training (stability resistance training, SRT) for six weeks. Gait and balance outcome parameters were assessed before, immediately after, and six weeks after the interventions. The primary outcome parameters were the functional reach test to evaluate balance and stride length to evaluate gait. Secondary outcomes included further gait analysis parameters, knee extension strength, the timed up and go test, and the six-minute walk test.

Results: The functional reach test results were significantly better after the intervention in both groups. Stride length increased significantly only in the GRT group. Several further gait parameters and the six-minute walk test improved in the GRT group, and the increase in gait speed was significantly higher than in the SRT group. The SRT group performed better after the intervention regarding the timed up and go test and knee extension strength, the latter being significantly more improved than in the SRT group. At six-week follow-up, the improvement in functional reach was maintained in the SRT group.

Conclusions: Integrative therapies, combining gait or balance training with resistance training, have specific positive effects in PD rehabilitation. More pronounced effects on gait parameters are achieved by GRT, while SRT has more impact on balance. Thus, the combination of both training methods might be particularly efficient in improving the mobility of PD patients.

Parkinson's disease (PD) is a progressive neurodegenerative disorder typically manifested by its motor symptoms. In addition, PD patients also suffer from many nonmotor symptoms (NMSs), such as apathy. Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the globus pallidus internus (GPi) are recommended as therapeutic interventions for PD, given their pronounced benefit in reducing troublesome dyskinesia. Apathy, a mood disorder recognized as a NMS of PD, has a negative impact on the prognosis of PD patients. However, the effect of STN-DBS and GPi-DBS on apathy is controversial. In the current meta-analysis, we analyzed apathy following bilateral STN-DBS and GPi-DBS in PD patients. Relevant literature was retrieved from public databases, including PubMed, Cochrane Library, and Embase. Studies were included in our analysis based on the following criterion: such studies should report apathy scores presurgery and postsurgery determined by using the Starkstein Apathy Scale or Apathy Evaluation Scale in patients receiving STN or GPi-DBS with at least three months of follow-up. Upon applying this strict criterion, a total of 13 out of 302 studies were included in our study. A mean difference (MD) and 95% confidence interval (CI) were calculated to show the change in apathy scores. We found a statistically significant difference between the presurgery and postsurgery scores in patients receiving STN-DBS (MD = 2.59, 95% CI = 2.23-2.96, P < 0.00001), but not in patients receiving GPi-DBS (MD = 0.32, 95% CI = -2.78-3.41, P=0.84). STN-DBS may worsen the condition of apathy, which may result from the reduction of dopaminergic medication. In conclusion, STN-DBS seems to relatively worsen the condition of apathy compared to GPi-DBS. Further studies should focus on the mechanisms of postoperatively apathy and the degree of apathy in STN-DBS versus GPi-DBS.

Introduction: Daytime sleepiness is a common nonmotor symptom in Parkinson's disease (PD) which is associated with decreased quality of life and perceived health. However, experiences of daytime sleepiness in people with PD have not been explored. The aim of this qualitative study was to explore experiences of daytime sleepiness in people with PD.

Materials and methods: Five women and seven men (42-82 years) with PD for 1.5 to 21 years and excessive daytime sleepiness (i.e., a score of >10 on the Epworth Sleepiness Scale) participated in the study. Data were collected through individual, semistructured, face-to-face interviews and analyzed with qualitative content analysis.

Results: Three themes of the experience of daytime sleepiness were revealed: (1) not an isolated phenomenon, (2) something to struggle against or accept, and (3) something beyond sleepiness. Conclusion. Daytime sleepiness is a complex nonmotor symptom in PD which manifests itself in several ways. Some experiences are similar, for instance, the attribution of daytime sleepiness to PD and its medical treatment. Differences depend on how sleepiness manifests itself, affects the person, and impacts daily life, as well as whether it causes feelings of embarrassment. Some participants needed to struggle against daytime sleepiness most of the time, and others had found a way to handle it, for example, with physical activity. However, sleepiness may also be used to benefit the person, for example, if they allow themselves to take a power nap to regain energy. The health care professionals can easily underestimate or misinterpret the prevalence and burden of daytime sleepiness because people with PD may describe daytime sleepiness as tiredness, drowsiness, or feeling exhausted, not as sleepiness.

Introduction: Genetic factors play an important role in Parkinson's disease (PD) risk. However, the genetic contribution to progression in Chinese PD patients has rarely been studied. This study investigated genetic associations with progression based on 30 PD risk loci common in a longitudinal cohort of Chinese PD patients and the Parkinson's Progression Markers Initiative (PPMI) cohort.

Methods: PD patients from the true world (TW) Chinese PD longitudinal cohort and the PPMI cohort with demographic information and assessment scales were assessed. A panel containing 30 PD risk single nucleotide polymorphisms was tested. Progression rates of each scale were derived from random-effect slope values of mixed-effects regression models. Progression rates of multiple assessments were combined by using principal component analysis (PCA) to derive scores for composite, motor, and nonmotor progression. The association of genetic polymorphism and separate scales or PCA progression was analysed via linear regression.

Results: In the Chinese PD cohort, MAOB rs1799836 was associated with progression based on the Montreal Cognitive Assessment, the top 3 principal components (PCs) of nonmotor PCA and PC1 of the composite PCA. In the PPMI cohort, both MDS-Unified Parkinson's Disease Rating Scale II and motor PC1 progression were associated with RIT2 rs12456492. The PARK16 haplotype was associated with Geriatric Depression Scale and the State-Trait Anxiety Inventory for Adults progression, and the SNCA haplotype was associated with the Hoehn-Yahr staging progression and motor PC1 progression. Ethnicity-stratified analysis showed that the association between MAOB rs1799836 and PD progression may be specific to Asian or Chinese patients.

Conclusion: MAOB rs1799836 was associated with the progression of nonmotor symptoms, especially cognitive impairment, and the composite progression of motor and nonmotor symptoms within our Chinese PD cohort. The RIT2 rs12456492 and SNCA haplotypes were associated with motor function decline, and the PARK16 haplotype was associated with progression in mood in the PPMI cohort.

Virtual reality (VR) is used in the rehabilitation of patients with Parkinson's disease (PD) in several studies. In VR trials, the motor, physical characteristics, and the degree of the disease are often well defined, while PD cognitive reserve is not. This systematic review was performed to define a cognitive profile for patients with PD who could best benefit from using VR to enhance functional motor aspects during rehabilitation. PubMed, Cochrane Library, Scopus, and Web of Sciences databases were analysed to identify randomized clinical trials (RCT) and randomized pilot trials that addressed the rehabilitation of motor symptoms in subjects with PD using VR. The included studies used Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) to evaluate the cognitive aspect. Only articles written in English and with full texts were considered. The risk of bias from all included studies was assessed based on the Cochrane risk-of-bias tool and the PRISMA guideline was considered. Eighteen articles were eligible for review, including three randomized pilot trials. All studies aimed to evaluate the effect of VR on the motor aspects typically affected by PD (balance, postural control, risk of falls, walking, and reaching). The most widely adopted approach has been nonimmersive VR, except for one study that used immersive VR. Both the benefits of physical activity on the motor symptoms of patients with PD and the impact of cognitive reserve during the rehabilitation of these patients were highlighted. The analysis of the results allowed us to outline the ideal cognitive profile of patients with PD who can benefit from the effects of rehabilitation using VR.

Parkinson's disease (PD) is a common neurodegenerative disorder. Rapid eye movement sleep behavior disorder (RBD) is one of the prodromal symptoms of PD. Studies have shown that brain information transmission is affected in PD patients. Consequently, we hypothesized that brain information transmission is impaired in RBD and PD. To prove our hypothesis, we performed functional connectivity (FC) and functional dynamics analysis of three aspects-based on the whole brain, within the resting-state network (RSN), and the interaction between RSNs-using normal control (NC) (n = 21), RBD (n = 24), and PD (n = 45) resting-state functional magnetic resonance imaging (rs-fMRI) data sets. Furthermore, we tested the explanatory power of FC and functional dynamics for the clinical features. Our results found that the global functional dynamics and FC of RBD and PD were impaired. Within RSN, the impairment concentrated in the visual network (VIS) and sensorimotor network (SMN), and the impaired degree of SMN in RBD was higher than that in PD. On the interaction between RSNs, RBD showed a widespread decrease, and PD showed a focal decrease which concentrated in SMN and VIS. Finally, we proved FC and functional dynamics were related to clinical features. These differences confirmed that brain information transmission efficiency and flexibility are impaired in RBD and PD, and these impairments are associated with the clinical features of patients.

Materials and methods: The neuroprotective effect of ketosis state prior to the onset of PD (preventive KD, KDp) was compared with that receiving KD after the onset (therapeutic KD, KDt) in the lipopolysaccharide- (LPS-) induced rat PD model. A total of 100 rats were randomly assigned to the following 4 groups: sham, LPS, LPS + KDp, and LPS + KDt groups.

Results: Significant dopamine deficient behaviors (rotational behavior and contralateral forelimb akinesia), upregulation of proinflammatory mediators (TNF-α, IL-1β, and IL-6), loss of dopaminergic neurons, reduction of mGluR5⁺ microglia cells, increase of TSPO⁺ microglia cells, reduction of H3K9 acetylation in the mGluR5 promoter region and mGluR5 mRNA expression, and decline in the phosphorylation levels of Akt/GSK-3β/CREB pathway were observed after the intervention of LPS (P < 0.01). TSPO and DAT PET imaging revealed the increased uptake of ¹⁸F-DPA-714 in substantia nigra and decreased uptake of ¹⁸F-FP-CIT in substantia nigra and striatum in LPS-treated rats (P < 0.001). These impairments were alleviated by the dietary intervention of KD, especially with the strategy of KDp (P < 0.05).

Conclusions: The anti-inflammatory effect of KD on PD was supposed to be related to the modulation of Akt/GSK-3β/CREB signaling pathway mediated by the histone acetylation of mGluR5 promotor region. The KD intervention should be initiated prior to the PD onset in high-risk population to achieve a more favorable outcome.

Problems in the respiratory system are the main cause of death in Parkinson's disease (PD). Ventilatory limitations can also be part of a vicious cycle involving physical-functional limitations (e.g., walking difficulties) and the patients' perception of fatigue. The objective of this study was to analyze the effects of an aquatic physical exercise intervention program on ventilatory parameters, perception of fatigue, and gait capacity in participants with PD. This quasi-experimental study had a single group with repeated measures in four assessments, proposing an aquatic physical exercise intervention program. The inclusion criteria encompassed being in levels 1 to 4 on the Hoehn and Yahr scale and having a medical certificate for the activities. Assessments took place at 3-month intervals between them-the first period was the control, the second following the intervention, and the third period was the follow-up. The intervention had 25 biweekly sessions over 3 months. A total of 13 people (71.3 ± 5.61 years old) participated in the intervention, without significant differences in the control period. Between the intervention assessments, they had statistically significant differences in MIP, MEP, FVC, Tiffeneau index, MVV, and fatigue. The study demonstrated that the aquatic physical exercise intervention was effective for ventilatory outcomes and fatigue in people with PD.