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Brain Sciences May 2024The role of the extracellular matrix (ECM) in Parkinson's disease (PD) is not well understood, even though it is critical for neuronal structure and signaling. This... (Review)
Review
The role of the extracellular matrix (ECM) in Parkinson's disease (PD) is not well understood, even though it is critical for neuronal structure and signaling. This systematic review identified the top deregulated ECM-related pathways in studies that used gene set enrichment analyses (GSEA) to document transcriptomic, proteomic, or genomic alterations in PD. PubMed and Google scholar were searched for transcriptomics, proteomics, or genomics studies that employed GSEA on data from PD tissues or cells and reported ECM-related pathways among the top-10 most enriched versus controls. Twenty-seven studies were included, two of which used multiple omics analyses. Transcriptomics and proteomics studies were conducted on a variety of tissue and cell types. Of the 17 transcriptomics studies (16 data sets), 13 identified one or more adhesion pathways in the top-10 deregulated gene sets or pathways, primarily related to cell adhesion and focal adhesion. Among the 8 proteomics studies, 5 identified altered overarching ECM gene sets or pathways among the top 10. Among the 4 genomics studies, 3 identified focal adhesion pathways among the top 10. The findings summarized here suggest that ECM organization/structure and cell adhesion (particularly focal adhesion) are altered in PD and should be the focus of future studies.
PubMed: 38928523
DOI: 10.3390/brainsci14060522 -
Sleep Medicine Jun 2024Parkinson's disease (PD) is a progressive neurodegenerative disorder, involving motor and non-motor symptoms (NMS). Sleep disturbances (SD) are the second most common... (Review)
Review
Parkinson's disease (PD) is a progressive neurodegenerative disorder, involving motor and non-motor symptoms (NMS). Sleep disturbances (SD) are the second most common NMS in PD and include rapid eye movement (REM) sleep behavior disorder (RBD), excessive daytime sleepiness and insomnia. Freezing of gait (FOG) is a gait impairment frequently reported in people with PD greatly hampering functional independence and quality of life. Presence of FOG has been associated with increased frequency and severity of NMS, including SD. Thus, the aim of this study was to systematically review the literature comparing the number of people with FOG in PD with (PD + SD) and without SD (PD-SD). By systematically searching PubMed and Web of Science databases to identify original peer-reviewed articles, 8 studies including 5251 people with PD (2025 PD + SD and 3226 PD-SD) met eligibility criteria and were included in the review. In 6 studies (4 studies investigating RBD, 2 studies investigating overall sleep quality), the group of PD + SD had higher prevalence of FOG compared with PD-SD. Although a limited number of studies, our findings suggest that PD + SD present more frequently FOG than PD-SD. More studies are required to investigate the possible mechanism underlying this association between FOG and sleep.
PubMed: 38908269
DOI: 10.1016/j.sleep.2024.06.001 -
Scientific Reports Jun 2024A network meta-analysis of randomized controlled trials was conducted to compare and rank the effectiveness of various noninvasive brain stimulation (NIBS) for... (Meta-Analysis)
Meta-Analysis
A network meta-analysis of randomized controlled trials was conducted to compare and rank the effectiveness of various noninvasive brain stimulation (NIBS) for Parkinson's disease (PD). We searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) databases from the date of database inception to April 30th, 2024. Two researchers independently screened studies of NIBS treatment in patients with PD based on inclusion and exclusion criteria. Two researchers independently performed data extraction of the included studies using an Excel spreadsheet and assessed the quality of the literature according to the Cochrane Risk of Bias Assessment Tool (RoB2). Network meta-analysis was performed in StataMP 17.0. A total of 28 studies involving 1628 PD patients were included. The results showed that HF-rTMS over the SMA (SMD = - 2.01; 95% CI [- 2.87, - 1.15]), HF-rTMS over the M1 and DLPFC (SMD = - 1.80; 95% CI [- 2.90, - 0.70]), HF-rTMS over the M1 (SMD = - 1.10; 95% CI [- 1.55, - 0.65]), a-tDCS over the DLPFC (SMD = - 1.08; 95% CI [- 1.90, - 0.27]), HF-rTMS over the M1 and PFC (SMD = - 0.92; 95% CI [- 1.71, - 0.14]), LF-rTMS over the M1 (SMD = - 0.72; 95% CI [- 1.17, - 0.28]), and HF-rTMS over the DLPFC (SMD = - 0.70; 95% CI [- 1.21, - 0.19]) were significantly improved motor function compared with sham stimulation. The SUCRA three highest ranked were HF-rTMS over the SMA (95.1%), HF-rTMS over the M1 and DLPFC (89.6%), and HF-rTMS over the M1 (73.0%). In terms of enhanced cognitive function, HF-rTMS over the DLPFC (SMD = 0.80; 95% CI [0.03,1.56]) was significantly better than sham stimulation. The SUCRA three most highly ranked were a-tDCS over the M1 (69.8%), c-tDCS over the DLPFC (66.9%), and iTBS over the DLPFC (65.3%). HF-rTMS over the M1 (SMD = - 1.43; 95% CI [- 2.26, - 0.61]) and HF-rTMS over the DLPFC (SMD = - 0.79; 95% CI [- 1.45, - 0.12)]) significantly improved depression. The SUCRA three highest ranked were HF-rTMS over the M1 (94.1%), LF-rTMS over the M1 (71.8%), and HF-rTMS over the DLPFC (69.0%). HF-rTMS over the SMA may be the best option for improving motor symptoms in PD patients. a-tDCS and HF-rTMS over the M1 may be the NIBS with the most significant effects on cognition and depression, separately.Trial registration: International Prospective Register of Systematic Review, PROSPERO (CRD42023456088).
Topics: Parkinson Disease; Humans; Network Meta-Analysis; Transcranial Magnetic Stimulation; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38902308
DOI: 10.1038/s41598-024-64196-0 -
Journal of Physiotherapy Jun 2024In people with Parkinson's disease, what is the effect of adding external cueing (ie, visual, auditory or somatosensorial cueing) to walking training compared with...
QUESTIONS
In people with Parkinson's disease, what is the effect of adding external cueing (ie, visual, auditory or somatosensorial cueing) to walking training compared with walking training alone in terms of walking, mobility, balance, fear of falling and freezing? Are any benefits carried over to participation or maintained beyond the intervention period?
DESIGN
Systematic review of randomised trials with meta-analysis.
PARTICIPANTS
Ambulatory adults with Parkinson's disease.
INTERVENTION
Walking training with external cueing compared with walking training without external cueing.
OUTCOME MEASURES
Walking (ie, speed, stride length and cadence), mobility, balance, fear of falling, freezing and participation.
RESULTS
Ten trials involving a total of 309 participants were included. The mean PEDro score of the included trials was 5 (range 4 to 8). Walking training with auditory cueing improved walking speed by 0.09 m/s (95% CI 0.02 to 0.15) more than walking training alone. Although the best estimate was that auditory cueing may also improve stride length by 5 cm, this estimate was imprecise (95% CI -2 to 11). The addition of visual cueing to walking training did not improve walking speed or stride length. Results regarding cadence, mobility, balance, fear of falling, and freezing and maintenance of benefits beyond the intervention period remain uncertain.
CONCLUSION
This systematic review provided low-quality evidence that walking training with auditory cueing is more effective than walking training alone for improving walking speed in Parkinson's disease. Cueing is an inexpensive and easy to implement intervention, so the mean estimate might be considered clinically worthwhile, although the confidence interval spans clinically trivial and worthwhile effects.
REGISTRATION
PROSPERO CRD42021255065.
PubMed: 38897907
DOI: 10.1016/j.jphys.2024.06.004 -
Frontiers in Aging Neuroscience 2024This meta-analysis aims to assess the effectiveness and safety of robot-assisted deep brain stimulation (DBS) surgery for Parkinson's disease(PD).
OBJECTIVE
This meta-analysis aims to assess the effectiveness and safety of robot-assisted deep brain stimulation (DBS) surgery for Parkinson's disease(PD).
METHODS
Four databases (Medline, Embase, Web of Science and CENTRAL) were searched from establishment of database to 23 March 2024, for articles studying robot-assisted DBS in patients diagnosed with PD. Meta-analyses of vector error, complication rate, levodopa-equivalent daily dose (LEDD), Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, and UPDRS IV were performed.
RESULTS
A total of 15 studies were included in this meta-analysis, comprising 732 patients with PD who received robot-assisted DBS. The pooled results revealed that the vector error was measured at 1.09 mm (95% CI: 0.87 to 1.30) in patients with Parkinson's disease who received robot-assisted DBS. The complication rate was 0.12 (95% CI, 0.03 to 0.24). The reduction in LEDD was 422.31 mg (95% CI: 68.69 to 775.94). The improvement in UPDRS, UPDRS III, and UPDRS IV was 27.36 (95% CI: 8.57 to 46.15), 14.09 (95% CI: 4.67 to 23.52), and 3.54 (95% CI: -2.35 to 9.43), respectively.
CONCLUSION
Robot-assisted DBS is a reliable and safe approach for treating PD. Robot-assisted DBS provides enhanced accuracy in contrast to conventional frame-based stereotactic techniques. Nevertheless, further investigation is necessary to validate the advantages of robot-assisted DBS in terms of enhancing motor function and decreasing the need for antiparkinsonian medications, in comparison to traditional frame-based stereotactic techniques.: PROSPERO(CRD42024529976).
PubMed: 38882524
DOI: 10.3389/fnagi.2024.1419152 -
Annals of Medicine and Surgery (2012) Jun 2024Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and...
BACKGROUND
Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and the risk of PD. The objective of the study is to compare the risk of Parkinson's disease (PD) between terazosin/alfuzosin/doxazosin (TZ/AZ/DZ) users and tamsulosin users.
METHODS
PubMed, Google Scholar, and Embase were systematically searched from inception to April 2023. Observational studies comparing the risk of PD among patients using different types of A1ARAs were included in the meta-analysis. The primary outcome was the hazard ratio (HR) with a 95% CI for the risk of occurrence of PD among A1ARAs users of two different classes.
RESULTS
This study was based on a total of 678 433 BPH patients, out of which 287 080 patients belonged to the TZ/AZ/DZ cohort and 391 353 patients belonged to the tamsulosin cohort. The pooled incidence of PD was higher in tamsulosin users (1.28%, 95% CI: 1.04-1.55%) than in TZ/AZ/DZ drug users (1.11%, 95% CI: 0.83-1.42%). The risk of occurrence of PD was significantly lower in patients taking TZ/AZ/DZ than tamsulosin (= 610,363, HR = 0.82, 95% CI = 0.71-0.94, = 0.01; I = 87.4%).
CONCLUSION
This meta-analysis demonstrated that patients with BPH who take TZ/AZ/DZ have a lower risk for developing PD than those who take tamsulosin.
PubMed: 38846867
DOI: 10.1097/MS9.0000000000002117 -
Clinical Rehabilitation Jun 2024To systematically evaluate the efficacy and safety of acupuncture therapy for neuropsychiatric symptoms in patients with Parkinson's disease.
OBJECTIVE
To systematically evaluate the efficacy and safety of acupuncture therapy for neuropsychiatric symptoms in patients with Parkinson's disease.
METHODS
We searched eight databases from their inception until 14 April 2024, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, China Science and Technology Periodical Database, and Wanfang Database. The search aimed to find randomized controlled trials assessing the effectiveness of acupuncture for neuropsychiatric symptoms in patients with Parkinson's disease. Literature screening and data extraction were performed independently by the authors. Meta-analysis was conducted using RevMan V.5.3 software, and Stata 17.0 software was used for detecting publication bias and performing sensitivity analysis.
RESULTS
Twenty-eight studies, involving 2148 participants, met the inclusion criteria. The meta-analysis revealed that acupuncture therapy improved depression-related scale scores (standardized mean difference (SMD) = -0.70, 95%CI [-0.98, -0.42], < 0.00001), anxiety-related scale scores (SMD = -0.78, 95% CI [-1.43, -0.14], = 0.02), Montreal Cognitive Assessment scores (weighted mean difference (WMD) = 2.74, 95% CI [2.43, 3.05], < 0.00001), Mini Mental State Examination scores (WMD = 2.36, 95% CI [0.78, 3.94], = 0.003), Yale-Brown Obsessive Compulsive Scale scores, and Parkinson's Disease Questionnaire-39 scores (WMD = -2.66, 95% CI [-4.83, -0.49], = 0.02) compared to controls.
CONCLUSION
This review supports the application of acupuncture to reduce the severity of neuropsychiatric symptoms including depression, anxiety, and impulse control disorders, and to improve cognition and quality of life in patients with Parkinson's disease. The adverse effects associated with acupuncture, either alone or as adjunctive therapy, were relatively minor.
PubMed: 38840478
DOI: 10.1177/02692155241258278 -
Journal of Stroke May 2024Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so... (Review)
Review
BACKGROUND AND PURPOSE
Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer's disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH).
METHODS
We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models.
RESULTS
We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P<0.0001). However, age was in general lower in the East-Asian cohorts.
CONCLUSION
The prevalence of CAA neuropathology in the general population, cognitively normal elderly, patients with AD, and patients with (lobar) ICH is similar in East-Asian and Western countries. In East-Asian cohorts reflecting the general population, cognitively normal elderly, and patients with ICH, strictly lobar microbleeds were less prevalent, likely due to their younger age. Consideration of potential presence of CAA is warranted in decisions regarding antithrombotic treatment and potential new anti-amyloid-β immunotherapy as treatment for AD in East-Asian and Western countries alike.
PubMed: 38836267
DOI: 10.5853/jos.2023.04287 -
Frontiers in Molecular Neuroscience 2024This study aims to visualize the trends and hotspots in the research of "ferroptosis in PD" and "pyroptosis in PD" through bibliometric analysis from the past to 2024.
OBJECTIVE
This study aims to visualize the trends and hotspots in the research of "ferroptosis in PD" and "pyroptosis in PD" through bibliometric analysis from the past to 2024.
METHODS
Literature was retrieved from the Web of Science Core Collection (WoSCC) from the past to February 16, 2024, and bibliometric analysis was conducted using Vosviewer and Citespace.
RESULTS
283 and 542 papers were collected in the field of "ferroptosis in PD" and "pyroptosis in PD." The number of publications in both fields has increased yearly, especially in "ferroptosis in PD," which will become the focus of PD research. China, the United States and England had extensive exchanges and collaborations in both fields, and more than 60% of the top 10 institutions were from China. In the fields of "ferroptosis in PD" and "pyroptosis in PD," the University of Melbourne and Nanjing Medical University stood out in terms of publication numbers, citation frequency, and centrality, and the most influential journals were Cell and Nature, respectively. The keyword time zone map showed that molecular mechanisms and neurons were the research hotspots of "ferroptosis in PD" in 2023, while memory and receptor 2 were the research hotspots of "pyroptosis in PD" in 2023, which may predict the future research direction.
CONCLUSION
This study provides insights into the development, collaborations, research themes, hotspots, and tendencies of "ferroptosis in PD" and "pyroptosis in PD." Overall situation of these fields is available for researchers to further explore the underlying mechanisms and potential treatments.
PubMed: 38817551
DOI: 10.3389/fnmol.2024.1400668 -
Biomedicine & Pharmacotherapy =... Jul 2024Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising... (Review)
Review
Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.
Topics: Activating Transcription Factor 4; Humans; Central Nervous System Diseases; Animals; Phytochemicals; Neuroprotective Agents
PubMed: 38795641
DOI: 10.1016/j.biopha.2024.116811