Parkinson's Disease最新文献

This study aimed to explore morphological changes of hippocampal subfields in patients with multiple system atrophy (MSA) with and without cognitive impairment using FreeSurfer-automated segmentation of hippocampal subfield techniques and their relationship with cognitive function. We enrolled 75 patients with MSA classified as cognitively impaired MSA (MSA-CI, n = 40) and cognitively preserved MSA (MSA-CP, n = 35), as well as 68 healthy controls. All participants underwent three-dimensional volume T1-weighted magnetic resonance imaging. The hippocampal subfield volume was measured using FreeSurfer version 7.2 and compared among groups. Regression analyses were performed between the hippocampal subfield volumes and cognitive variables. Compared with healthy controls, the volume of the right cornu ammonis (CA) 2/3 was significantly lower in the MSA-CI group (P=0.029) and that of the left fimbria was significantly higher in the MSA-CP group (P=0.046). Results of linear regression analysis showed that the right CA2/3 volume was significantly correlated with the Frontal Assessment Battery score in patients with MSA (adjusted R ² = 0.282, β = 0.227, and P=0.041). The hippocampal subfield volume decreased in patients with MSA-CI, even at the early disease stages. Specific structural changes in the hippocampus might be associated with cognitive deficits in MSA.

Background: Cognitive impairment is common in Parkinson's disease (PD) and associated with lower quality of life. Cognitive impairment in PD manifests differently to other dementia pathologies. Provision of optimal care requires knowledge about the support needs of this population.

Methods: Eleven people with PD and cognitive impairment (PwP), 10 family caregivers, and 27 healthcare professionals were purposively sampled from across the United Kingdom. Semistructured interviews were conducted in 2019-2021, audio-recorded, transcribed, and analysed using reflexive thematic analysis.

Results: Cognitive impairment in PD conveyed increased complexity for clinical management and healthcare interactions, the latter driven by multifactorial communication difficulties. Techniques that helped included slow, simple, and single messages, avoiding topic switching. Information and emotional support needs were often unmet, particularly for caregivers. Diagnostic pathways were inconsistent and awareness of cognitive impairment in PD was poor, both contributing to underdiagnosis. Many felt that PwP and cognitive impairment fell through service gaps, resulting from disjointed, nonspecific, and underresourced services. Personalised care was advocated through tailoring to individual needs of PwP and caregivers facilitated by flexibility, time and continuity within services, and supporting self-management.

Conclusions: This study highlights unmet need for people with this complex condition. Clinicians should adapt their approach and communication techniques for this population and provide tailored information and support to both PwP and caregivers. Services need to be more streamlined and collaborative, providing more time and flexibility. There is a need for wider awareness and deeper understanding of this condition and its differences from other types of dementia.

Background: Transcranial sonography (TCS) is a noninvasive test that can reveal structural changes in the substantia nigra (SN) in Parkinson's disease (PD). The purpose of this study was to investigate the relationship between SN signatures and clinical features in PD patients in a multiethnic region of China.

Methods: A total of 147 patients with PD were included in the study, and all of whom had underwent a TCS examination. Clinical information was collected from PD patients, and motor and nonmotor symptoms were assessed using assessment scales.

Results: There were differences in the substantia nigra hyperechogenicity (SNH) area between age of onset, visual hallucinations (VH), and UPDRS3.0 II scores (P < 0.05), patients with late onset PD had a greater SNH area than early onset (0.326 ± 0.352 vs. 0.171 ± 0.194), and PD patients presenting with VH had a greater SNH area than those without hallucinations (0.508 ± 0.670 vs. 0.278 ± 0.659), and further multifactorial analysis showed that a high SNH area was an independent risk factor for development of VH. The area under the ROC curve for predicting VH from the SNH area in PD patients was 0.609 (95% CI: 0.444-0.774). There was a positive correlation between the SNH area and UPDRS3.0-II scores, but further multifactorial analysis showed that SNH was not an independent predictor of the UPDRS3.0-II score.

Conclusion: A high SNH area is an independent risk factor for development of VH, there is a positive correlation between the SNH area and UPDRS3.0 II score, and TCS has guiding significance in predicting clinical VH symptoms and activities of daily living in PD patients.

Background: In Parkinson's disease (PD), dopamine deficiency is present not only in the nigrostriatal pathway but also in the retinal and visual pathways. Optic coherence tomography (OCT) can be used as morphological evidence of visual influence from early nonmotor symptoms. The aim of this study was to investigate the relationship of OCT and visual evoked potentials (VEPs) of eyes with the severity of clinical findings and ocular findings in PD.

Methods: A group of 42 patients diagnosed with idiopathic PD and a control group of 29 people between the ages of 45-85 were included in our study. VEP was recorded in the patient and control groups. OCT measurement was made with the Optovue spectral-domain device. Foveal thickness and macular volume were measured in the foveal region and in the parafoveal and perifoveal regions in the temporal, superior, nasal, and inferior quadrants. RNFL (retinal nerve fiber layer) was measured in temporal, superior, nasal, and inferior quadrants. Ganglion cell complex (GCC) was evaluated in the superior and inferior quadrants. Using the UPDRS clinical scale, the relationship between measurements and the differences between the control group and the patient group were evaluated.

Results: Among the OCT values in our study, foveal, parafoveal, perifoveal thickness, macular volume, RNFL, and GCC measurements were performed for the right and left eyes, and no difference was found between the patient group and the control group. There was no difference in VEP amplitude and latency values between the patient and control groups. The relationships between UPDRS and modified Hoehn Yahr staging and OCT and VEP measurements in the patient revealed no correlation.

Conclusions: Studies on whether OCT measurements can functionally be a marker or which segments are more valuable for disease progression in patients with PD are needed. Visual dysfunction in PD cannot be attributed only to retinal pathology; however, the retina may provide monitoring of the status of dopaminergic neurodegeneration and axonal loss in PD.

Background: The complex nature of late-stage Parkinson's requires multiagency support and leads to an increased burden on family members who assume a multiplicity of responsibilities. The aim of this study is to further understand the lived experiences of family-caregivers and their perception of, and satisfaction with, service provision.

Methods: This qualitative substudy was a part of the European multicentre Care of Late-Stage Parkinsonism (CLaSP) project. Purposive sampling resulted in a sample of eleven family-caregivers of people with late-stage Parkinson's, who were interviewed using semistructured open-ended questions. Thematic analysis followed. Findings. Three overarching themes were developed from the data: ensuring continuous support is vital to providing care at home, perceiving unmet service provision needs, and advocating and co-ordinating all aspects of care take their toll. These themes include not only experience of services that caregivers find supportive in order to deliver care but also of disjointed care between multiple agencies, a perceived lack of Parkinson's expertise, and there was a lack of anticipatory future planning. The constancy and scope of the family-caregiver role is described, including the need to project manage multiple aspects of care with multiple agencies, to be an advocate, and to assume new roles such as managing finances. Multiple losses were reported, which in part was mitigated by gaining expertise through information and support from professionals and organised and informal support.

Conclusion: The intricacies and consequences of the family-caregivers' role and their experience of service provision indicate the need to acknowledge and consider their role and needs, fully involve them in consultations and provide information and joined-up support to improve their well-being, and ensure their continuous significant contribution to the ongoing care of the person with Parkinson's.

Background: Gastrointestinal symptoms (GIS) in people with Parkinson's disease (PwP) are often underreported and may remain untreated. Constipation is a common nonmotor symptom that can adversely affect health-related quality of life (QoL); however, the impact of other GIS has not been adequately investigated.

Objectives: To investigate the relationship between QoL and constipation using the Bristol Stool Chart, bowel movement frequency, and a perceived constipation measure; and to explore the relationship between QoL and other GIS in an Australian PD cohort.

Methods: The impact of constipation and other GIS on QoL, as measured using the PDQ-39 scale, was assessed in a cohort of 144 (89 males, 55 females) clinic-attending PwP. Constipation was assessed using the Bristol Stool Chart as well as a composite constipation measure, and the Gastrointestinal Symptom Rating Scale (GSRS) was used to rate other GIS. Covariate corrected linear regression models were utilised to determine significant associations between GIS and QoL scores.

Results: Individual and combined constipation measures were significantly associated with poorer QoL (p=0.032 and p=0.002, respectively). Analysis of GSRS symptom domains showed that in addition to symptoms of gastrointestinal hypomotility, a number of other symptoms such as increased eructation and increased flatus were also associated with poorer QoL.

Conclusions: The findings point to the importance of GIS as contributor to health-related QoL in PwP. A better understanding of the relationship between GIS and QoL will help facilitate the development of more effective screening and treatment programs to improve symptom management and QoL for PwP.

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.