Summary
Neurodegenerative diseases are a heterogeneous group of disorders that are incurable and characterized by the progressive degeneration of the function and structure of the central nervous ...system (CNS) for reasons that are not yet understood. Neurodegeneration is the umbrella term for the progressive death of nerve cells and loss of brain tissue. Because of their high energy requirements, neurons are especially vulnerable to injury and death from dysfunctional mitochondria. Widespread damage to mitochondria causes cells to die because they can no longer produce enough energy. Several lines of pathological and physiological evidence reveal that impaired mitochondrial function and dynamics play crucial roles in aging and pathogenesis of neurodegenerative diseases. As mitochondria are the major intracellular organelles that regulate both cell survival and death, they are highly considered as a potential target for pharmacological‐based therapies. The purpose of this review was to present the current status of our knowledge and understanding of the involvement of mitochondrial dysfunction in pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) and the importance of mitochondrial biogenesis as a potential novel therapeutic target for their treatment. Likewise, we highlight a concise overview of the key roles of mitochondrial electron transport chain (ETC.) complexes as well as mitochondrial biogenesis regulators regarding those diseases.
Spinocerebellar ataxias (SCA) comprise a rare, genetic subgroup within the degenerative ataxias and are dominantly inherited, with up to 48 recognized genetic subtypes. While an updated review on the ...management of degenerative ataxia is published recently, an evidence-based review focussed on the management of SCA is lacking. Here, we reviewed the pharmacological and non-pharmacological management of SCA by conducting a systematic review on Medline Ovid and Scopus. Of 29,284 studies identified, 47 studies (pharmacological:
n
= 25; non-pharmacological:
n
= 22) that predominantly involved SCA patients were included. Twenty studies had a high risk of bias based on the Cochrane’s Collaboration risk of bias tool. As per the European Federation of Neurological Societies 2004 guideline for therapeutic intervention, the remaining 27 studies were of Class I (
n
= 4) and Class II (
n
= 23) evidence. Only two therapies had Level A recommendations for the management of ataxia symptoms: riluzole and immediate in-patient neurorehabilitation. Ten therapies had Level B recommendations for managing ataxia symptoms and require further investigations with better study design. These include high dose valproate acid, branched-chain amino acid, intravenous trehalose; restorative rehabilitation using cycling regimen and videogame; and cerebellar stimulations using transcranial direct current stimulation and transcranial magnetic stimulation. Lithium and coaching on psychological adjustment received Level B recommendation for depressive symptoms and quality of life, respectively. Heterogeneous study designs, different genotypes, and non-standardized clinical measures alongside short duration and small sample sizes may hamper meaningful clinical translation. Therefore, rating of recommendations only serve as points of reference.
The second most prevalent neurodegenerative disorder in the elderly is Parkinson's disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more ...evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish (
) are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as
and
. The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models.
Spinocerebellar ataxia type 3 (SCA3), the commonest dominantly inherited ataxia worldwide, is characterized by disruption in the cerebellar-cerebral and striatal-cortical networks. Findings on ...SCA3-associated cognitive impairments are mixed. The classification models, tests and scoring systems used, language, culture, ataxia severity, and depressive symptoms are all potential confounders in neuropsychological assessments and may have contributed to the heterogeneity of the neurocognitive profile of SCA3. We conducted a systematic review of studies evaluating neurocognitive function in SCA3 patients. Of 1304 articles identified, 15 articles met the eligibility criteria. All articles were of excellent quality according to the National Institutes of Health quality assessment tool for case–control studies. In line with the disrupted cerebellar-cerebral and striatal-cortical networks in SCA3, this systematic review found that the neurocognitive profile of SCA3 is characterized by a core impairment of executive function that affects processes such as nonverbal reasoning, executive aspects of language, and recall. Conversely, neurocognitive domains such as general intelligence, verbal reasoning, semantic aspect of language, attention/processing speed, recognition, and visuospatial perception and construction are relatively preserved. This review highlights the importance of evaluating neurocognitive function in SCA3 patients. Considering the negative impact of cognitive and affective impairment on quality of life, this review points to the profound impairments that existing or future treatments should prioritize.
Gait analysis is an essential tool for detecting biomechanical irregularities, designing personalized rehabilitation plans, and enhancing athletic performance. Currently, gait assessment depends on ...either visual observation, which lacks consistency between raters and requires clinical expertise, or instrumented evaluation, which is costly, invasive, time-consuming, and requires specialized equipment and trained personnel. Markerless gait analysis using 2D pose estimation techniques has emerged as a potential solution, but it still requires significant computational resources and human involvement, making it challenging to use. This research proposes an automated method for temporal gait analysis that employs the MediaPipe Pose, a low-computational-resource pose estimation model. The study validated this approach against the Vicon motion capture system to evaluate its reliability. The findings reveal that this approach demonstrates good (ICC
> 0.75) to excellent (ICC
> 0.90) agreement in all temporal gait parameters except for double support time (right leg switched to left leg) and swing time (right), which only exhibit a moderate (ICC
> 0.50) agreement. Additionally, this approach produces temporal gait parameters with low mean absolute error. It will be useful in monitoring changes in gait and evaluating the effectiveness of interventions such as rehabilitation or training programs in the community.
Training caregivers and persons with Parkinson Disease (PwPD) is crucial to provide them with adequate knowledge and care skills in preparation for the Parkinson disease (PD) progression. This review ...will systematically evaluate the effect of structured training programs on the mobility and quality of life (QoL) of PwPD. In addition, the effect of such training programs on the QoL, burden of caregiving, and knowledge of PD among adult caregivers of PwPD will also be evaluated.
Systematic and comprehensive search of relevant studies will be conducted using electronic databases such as Cochrane Library, EBSCOhost, PubMed, SCOPUS, and Web of Science. The title, abstract, keywords, and full texts will be screened for eligibility. Studies to be selected are randomized controlled trials (RCT) from inception until April 2023. Studies based on structured PD training either in the form of training, education, program, multidisciplinary approach, or self-management targeted at both PwPD and their adult caregivers will be selected. Only full-text articles available in the English language will be included. Full-text articles will be inspected by 2 independent reviewers to produce the final set of articles that meet the eligibility criteria. A third reviewer will be engaged if no consensus is achieved between the first and second reviewers. Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) will be used to evaluate the quality of papers and inform the risk of bias.
This review will provide an outlook on the effects of structured PD training programs on mobility and QoL of PwPD. In addition, it will provide insight into the effects of such training on the caregivers' burden, knowledge of PD, and QoL.
This review findings may help clinicians and researchers to understand the effect of structured and comprehensive PD training programs for PwPD and their adult caregiver.
We determined the effectiveness of a multi-strain probiotic (Hexbio®) containing microbial cell preparation MCP®BCMC® on constipation symptoms and gut motility in PD patients with constipation.
PD ...patients with constipation (ROME III criteria) were randomized to receive a multi-strain probiotic (Lactobacillus sp and Bifidobacterium sp at 30 X 109 CFU) with fructo-oligosaccaride or placebo (fermented milk) twice daily for 8 weeks. Primary outcomes were changes in the presence of constipation symptoms using 9 items of Garrigues Questionnaire (GQ), which included an item on bowel opening frequency. Secondary outcomes were gut transit time (GTT), quality of life (PDQ39-SI), motor (MDS-UPDRS) and non-motor symptoms (NMSS).
Of 55 recruited, 48 patients completed the study: 22 received probiotic and 26 received placebo. At 8 weeks, there was a significantly higher mean weekly BOF in the probiotic group compared to placebo SD 4.18 (1.44) vs SD 2.81(1.06); (mean difference 1.37, 95% CI 0.68, 2.07, uncorrected p<0.001). Patients in the probiotic group reported five times higher odds (odds ratio = 5.48, 95% CI 1.57, 19.12, uncorrected p = 0.008) for having higher BOF (< 3 to 3-5 to >5 times/week) compared to the placebo group. The GTT in the probiotic group 77.32 (SD55.35) hours reduced significantly compared to placebo 113.54 (SD 61.54) hours; mean difference -36.22, 95% CI -68.90, -3.54, uncorrected p = 0.030). The mean change in GTT was 58.04 (SD59.04) hour vs 20.73 (SD60.48) hours respectively (mean difference 37.32, 95% CI 4.00, 70.63, uncorrected p = 0.028). No between-groups differences were observed in the NMSS, PDQ39-SI, MDS-UPDRS II and MDS-UPDRS III scores. Four patients in the probiotics group experienced mild reversible side effects.
This study showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation.
•Recognize different emotional states using brain functional connectivity.•EEG change is significantly different among emotional states of PD patients.•Highest classification results for the proposed ...bispectral functional connectivity index.•PD patients exists decline in cortical connectivity during emotion processing.
Successful emotional communication is crucial for social interactions and social relationships. Parkinson’s Disease (PD) patients have shown deficits in emotional recognition abilities although the research findings are inconclusive. This paper presents an investigation of six emotions (happiness, sadness, fear, anger, surprise, and disgust) of twenty non-demented (Mini-Mental State Examination score >24) PD patients and twenty Healthy Controls (HCs) using Electroencephalogram (EEG)-based Brain Functional Connectivity (BFC) patterns. The functional connectivity index feature in EEG signals is computed using three different methods: Correlation (COR), Coherence (COH), and Phase Synchronization Index (PSI). Further, a new functional connectivity index feature is proposed using bispectral analysis. The experimental results indicate that the BFC change is significantly different among emotional states of PD patients compared with HC. Also, the emotional connectivity pattern classified using Support Vector Machine (SVM) classifier yielded the highest accuracy for the new bispectral functional connectivity index. The PD patients showed emotional impairments as demonstrated by a poor classification performance. This finding suggests that decrease in the functional connectivity indices during emotional stimulation in PD, indicating functional disconnections between cortical areas.
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