Parkinson's Disease最新文献

Background: Non-motor symptoms of Parkinson's disease (PD) such as cognitive impairment are common and decrease patient quality of life and daily functioning. While no pharmacological treatments have effectively alleviated these symptoms to date, non-pharmacological approaches such as cognitive remediation therapy (CRT) and physical exercise have both been shown to improve cognitive function and quality of life in people with PD.

Objective: This study aims to determine the feasibility and impact of remote CRT on cognitive function and quality of life in patients with PD participating in an organized group exercise program.

Methods: Twenty-four subjects with PD recruited from Rock Steady Boxing (RSB), a non-contact group exercise program, were evaluated using standard neuropsychological and quality of life measures and randomized to the control or intervention group. The intervention group attended online CRT sessions for one hour, twice a week for 10 weeks, engaging in multi-domain cognitive exercises and group discussion.

Results: Twenty-one subjects completed the study and were reevaluated. Comparing groups over time, the control group (n = 10) saw a decline in overall cognitive performance that trended towards significance (p = 0.05) and a statistically significant decrease in delayed memory (p = 0.010) and self-reported cognition (p = 0.011). Neither of these findings were seen in the intervention group (n = 11), which overwhelmingly enjoyed the CRT sessions and attested to subjective improvements in their daily lives.

Conclusions: This randomized controlled pilot study suggests that remote CRT for PD patients is feasible, enjoyable, and may help slow the progression of cognitive decline. Further trials are warranted to determine the longitudinal effects of such a program.

Parkinson's disease (PD) is the second most common neurodegenerative disease, with significant socioeconomic burdens. One of the crucial pathological features of PD is the loss of dopaminergic neurons in the substantia nigra (SN). However, the exact pathogenesis remains unknown. Moreover, therapies to prevent neurodegenerative progress are still being explored. We performed bioinformatics analysis to identify candidate genes and molecular pathogenesis in the SN of patients with PD. We analyzed the expression profiles, GSE49036 and GSE7621, which included 31 SN tissues in PD samples and 17 SN tissues in healthy control samples, and identified 86 common differentially expressed genes (DEGs). Then, GO and KEGG pathway analyses of the identified DEGs were performed to understand the biological processes and significant pathways of PD. Subsequently, a protein-protein interaction network was established, with 15 hub genes and four key modules which were screened in this network. The expression profiles, GSE8397 and GSE42966, were used to verify these hub genes. We demonstrated a decrease in the expression levels of 14 hub genes in the SN tissues of PD samples. Our results indicated that, among the 14 hub genes, DRD2, SLC18A2, and SLC6A3 may participate in the pathogenesis of PD by influencing the function of the dopaminergic synapse. CACNA1E, KCNJ6, and KCNB1 may affect the function of the dopaminergic synapse by regulating ion transmembrane transport. Moreover, we identified eight microRNAs (miRNAs) that can regulate the hub genes and 339 transcription factors (TFs) targeting these hub genes and miRNAs. Subsequently, we established an mTF-miRNA-gene-gTF regulatory network. Together, the identification of DEGs, hub genes, miRNAs, and TFs could provide better insights into the pathogenesis of PD and contribute to the diagnosis and therapies.

Introduction: Parkinson's disease (PD) is the second most common neurological disorder. Patients with PD were affected by the COVID-19 pandemic in many different ways. This study's principal purpose is to assess PD patients' vulnerability to COVID-19 and its consequences.

Method: This systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. A thorough search was conducted in the Medline (through PubMed) and Scopus databases from inception to January 30, 2022. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to evaluate the studies.

Results: Most of the studies (38%) had been conducted in Italy. Of the total number of studies, 17 (58%) were cross-sectional, seven (22%) were cohort, four (12%) were quasiexperimental, two (6%) were case-control, and one (3%) was a qualitative study. The PD duration in patients ranged from 3.26 to 13.40 years (IQR1: 5.7 yrs., median: 3.688 yrs., and IQR3: 8.815 yrs.). Meanwhile, the sample size ranged from 12 to 30872 participants (IQR1: 46, median: 96, and IQR3: 211). Despite worsening PD symptoms in the targeted population (persons with COVID-19 and Parkinson's disease), some studies found PD to be a risk factor for more severe COVID-19 disease. There are many adverse effects during the pandemic period in PD patients such as abnormalities of motor, nonmotor functioning, clinical outcomes, activities of daily living, and other outcomes.

Conclusion: This study confirmed the negative effect of the COVID-19 pandemic on health-related quality of life and its determinants in patients with PD and their caregivers. Thus, due to the worsening symptoms of PD patients in the current pandemic, these people should be given more care and supervision to minimize their coronavirus exposure.

Introduction: Fatigue and orthostatic hypotension (OH) are common and disabling nonmotor symptoms (NMSs) of Parkinson's disease (PD), but none of the studies have reported on the longitudinal association between fatigue and OH.

Methods: Drug-naïve PD patients were recruited from a hospital-based cohort and evaluated with the Parkinson Fatigue Scale (PFS), head-up tilt test, Unified PD Rating Scale, Hoehn and Yahr stage, Montreal Cognitive Assessment, Scale for Outcomes in PD-Autonomic (SCOPA-AUT), Beck Depression Inventory (BDI), Beck Anxiety Inventory, PD Sleep Scale, and medications at the baseline and follow-up visits.

Results: A total of 80 patients were included, and the mean ages were 66.6 and 63.8 years in the fatigue and nonfatigue groups, respectively. The prevalence of fatigue was 17.5% (14/80) at the baseline and follow-up (mean follow-up: 23.3 ± 9.9 months). The prevalence of OH in the fatigue group was 57.1%, and it was significantly higher than that of the nonfatigue group. Six of the 14 patients (42.9%) in the fatigue group had persistent fatigue at the follow-up, and eight of them (57.1%) converted to the nonfatigue group. Logistic regression analysis demonstrated that the changes of BDI and the presence of OH at the baseline were the predictors for fatigue in drug-naïve PD.

Conclusion: Fatigue is a common NMS in PD but can vary depending on the disease course. OH and depression are the most relevant predictors for the development of fatigue in drug-naïve PD. The present study suggests that the management of autonomic symptoms and depression might be helpful for managing fatigue in PD.

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.