Randomized double-blind placebo-controlled trial of the effects of oral trehalose in spinocerebellar ataxia type 3: An interim analysis.

INTRODUCTION: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease characterized by increasingly worsening ataxia and non-ataxia features, negatively impacting patients' quality of life. This study was designed to test formally evaluate whether oral trehalose was effective in SCA3 patients. METHODS: In this double-blind, randomized controlled trial, SCA3 patients received either 100 g oral trehalose or 30 g maltose to improve ataxia severity over six months. We also measured other clinical (non-ataxia), patient-reported (quality of life, motivations), and safety endpoints. An unscheduled interim analysis was conducted using two-way ANOVAs to analyze the interaction between time (baseline, 3-months, 6-months) and intervention (Trehalose vs. Placebo). RESULTS: Fifteen participants (Trehalose = 7 vs. Placebo = 8) completed the study at the time of interim analysis. There was no interaction effect on the ataxia severity, and available data suggested an estimated sample size of 132 (66 per arm) SCA3 patients required to demonstrate changes in a 6-month trial. There were significant interaction effects for executive function (ƞ2 = 0.28-0.43). Safety data indicated that 100 g oral trehalose was well-tolerated. CONCLUSION: We performed an unplanned interim analysis due to a slow recruitment rate. The new estimated sample size was deemed unfeasible, leading to premature termination of the clinical trial. In this small, current sample of SCA3 patients, 100 g oral trehalose did not differentially impact on ataxia severity compared to placebo. Interestingly, our findings may suggest an improvement in executive function. Future efforts will require a large multi-country, multi-center study to investigate the potential effect of trehalose.

Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes.

Automated Gait Analysis Based on a Marker-Free Pose Estimation Model.

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(2,1) > 0.75) to excellent (ICC(2,1) > 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(2,1) > 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.

The multifaceted impact of structured training program on persons with Parkinson disease and their adult caregiver: A protocol for a systematic review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Genetic Movement Disorders Commonly Seen in Asians.

The increasing availability of molecular genetic testing has changed the landscape of both genetic research and clinical practice. Not only is the pace of discovery of novel disease-causing genes accelerating but also the phenotypic spectra associated with previously known genes are expanding. These advancements lead to the awareness that some genetic movement disorders may cluster in certain ethnic populations and genetic pleiotropy may result in unique clinical presentations in specific ethnic groups. Thus, the characteristics, genetics and risk factors of movement disorders may differ between populations. Recognition of a particular clinical phenotype, combined with information about the ethnic origin of patients could lead to early and correct diagnosis and assist the development of future personalized medicine for patients with these disorders. Here, the Movement Disorders in Asia Task Force sought to review genetic movement disorders that are commonly seen in Asia, including Wilson's disease, spinocerebellar ataxias (SCA) types 12, 31, and 36, Gerstmann-Sträussler-Scheinker disease, PLA2G6-related parkinsonism, adult-onset neuronal intranuclear inclusion disease (NIID), and paroxysmal kinesigenic dyskinesia. We also review common disorders seen worldwide with specific mutations or presentations that occur frequently in Asians.

Neurological manifestations in SARS-CoV-2 infection: A single-center cross-sectional study in Malaysia.

Background: Neurological involvement associated with SARS-CoV-2 infection has been reported from different regions of the world. However, data from South East Asia are scarce. We described the neurological manifestations and their associated factors among the hospitalized COVID-19 patients from an academic tertiary hospital in Malaysia. Methods: A cross-sectional observational study of hospitalized COVID-19 patients was conducted. The neurological manifestations were divided into the self-reported central nervous system (CNS) symptoms, stroke associated symptoms, symptoms of encephalitis or encephalopathy and specific neurological complications. Multiple logistic regression was performed using demographic and clinical variables to determine the factors associated with outcome. Results: Of 156 hospitalized COVID-19 patients with mean age of 55.88 ± 6.11 (SD) years, 23.7% developed neurological complications, which included stroke, encephalitis and encephalopathy. Patients with neurological complications were more likely to have diabetes mellitus (p = 0.033), symptoms of stroke [limb weakness (p < 0.001), slurred speech (p < 0.001)]; and encephalitis or encephalopathy [confusion (p < 0.001), forgetfulness (p = 0.006) and seizure (p = 0.019)]. Unvaccinated patients had a 4.25-fold increased risk of having neurological complications (adjusted OR = 4.25; 95% CI: 1.02, 17.71, p = 0.047). Anosmia and dysgeusia were less associated with neurological complications (adjusted OR = 0.22; 95% CI: 0.05, 0.96, p = 0.044). The odds of neurological complications were increased by 18% in patients with leukocytosis (adjusted OR = 1.18, 95% CI: 1.003, p = 0.0460). Conclusions: Stroke, encephalitis and encephalopathy were the common neurological complications from our study. Diabetes mellitus, presence of symptoms of stroke, symptoms of encephalitis or encephalopathy, leukocytosis, and being unvaccinated against COVID-19 were the associated risk factors of developing neurological complications.

Brain MRI Volumetry Analysis in an Indonesian Family of SCA 3 Patients: A Case-Based Study.

Introduction: Spinocerebellar ataxia type-3 (SCA3) is an adult-onset autosomal dominant neurodegenerative disease. It is caused by expanding of CAG repeat in ATXN3 gene that later on would affect brain structures. This brain changes could be evaluated using brain MRI volumetric. However, findings across published brain volumetric studies have been inconsistent. Here, we report MRI brain volumetric analysis in a family of SCA 3 patients, which included pre-symptomatic and symptomatic patients. Methodology: The study included affected and unaffected members from a large six-generation family of SCA 3, genetically confirmed using PolyQ/CAG repeat expansion analysis, Sanger sequencing, and PCR. Clinical evaluation was performed using Scale for the Assessment and Rating of Ataxia (SARA). Subjects' brains were scanned using 3.0-T MRI with a 3D T1 BRAVO sequence. Evaluations were performed by 2 independent neuroradiologists. An automated volumetric analysis was performed using FreeSurfer and CERES (for the cerebellum). Result: We evaluated 7 subjects from this SCA3 family, including 3 subjects with SCA3 and 4 unaffected subjects. The volumetric evaluation revealed smaller brain volumes (p < 0.05) in the corpus callosum, cerebellar volume of lobules I-II, lobule IV, lobule VIIB and lobule IX; and in cerebellar gray matter volume of lobule IV, and VIIIA; in the pathologic/expanded CAG repeat group (SCA3). Conclusion: Brain MRI volumetry of SCA3 subjects showed smaller brain volumes in multiple brain regions including the corpus callosum and gray matter volumes of several cerebellar lobules.

Magnetic Resonance Imaging and Its Clinical Correlation in Spinocerebellar Ataxia Type 3: A Systematic Review.

Background: Spinocerebellar ataxia type 3 (SCA3) is a complex cerebrocerebellar disease primarily characterized by ataxia symptoms alongside motor and cognitive impairments. The heterogeneous clinical presentation of SCA3 necessitates correlations between magnetic resonance imaging (MRI) and clinical findings in reflecting progressive disease changes. At present, an attempt to systematically examine the brain-behavior relationship in SCA3, specifically, the correlation between MRI and clinical findings, is lacking. Objective: We investigated the association strength between MRI abnormality and each clinical symptom to understand the brain-behavior relationship in SCA3. Methods: We conducted a systematic review on Medline and Scopus to review studies evaluating the brain MRI profile of SCA3 using structural MRI (volumetric, voxel-based morphometry, surface analysis), magnetic resonance spectroscopy, and diffusion tensor imaging, including their correlations with clinical outcomes. Results: Of 1,767 articles identified, 29 articles met the eligibility criteria. According to the National Institutes of Health quality assessment tool for case-control studies, all articles were of excellent quality. This systematic review found that SCA3 neuropathology contributes to widespread brain degeneration, affecting the cerebellum and brainstem. The disease gradually impedes the cerebral cortex and basal ganglia in the late stages of SCA3. Most findings reported moderate correlations (r = 0.30-0.49) between MRI features in several regions and clinical findings. Regardless of the MRI techniques, most studies focused on the brainstem and cerebellum. Conclusions: Clinical findings suggest that rather than individual brain regions, the connectivity between different brain regions in distributed networks (i.e., cerebellar-cerebral network) may be responsible for motor and neurocognitive function in SCA3. This review highlights the importance of evaluating the progressive changes of the cerebellar-cerebral networks in SCA3 patients, specifically the functional connectivity. Given the relative lack of knowledge about functional connectivity on SCA3, future studies should investigate possible functional connectivity abnormalities in SCA3 using fMRI.

Pharmacological and non-pharmacological management of spinocerebellar ataxia: A systematic review.

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.

Neurocognitive Changes in Spinocerebellar Ataxia Type 3: A Systematic Review with a Narrative Design.

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.

Aberrant Neurogliovascular Unit Dynamics in Cerebral Small Vessel Disease: A Rheological Clue to Vascular Parkinsonism.

The distinctive anatomical assemble and functionally discrete multicellular cerebrovasculature dynamics confer varying rheological and blood-brain barrier permeabilities to preserve the integrity of cerebral white matter and its neural microenvironment. This homeostasis intricately involves the glymphatic system that manages the flow of interstitial solutes, metabolic waste, and clearance through the venous circulation. As a physiologically integrated neurogliovascular unit (NGVU) serving a particularly vulnerable cerebral white matter (from hypoxia, metabolic insults, infection, and inflammation), a likely insidious process over a lifetime could inflict microenvironment damages that may lead to pathological conditions. Two such conditions, cerebral small vessel disease (CSVD) and vascular parkinsonism (VaP), with poorly understood pathomechanisms, are frequently linked to this brain-wide NGVU. VaP is widely regarded as an atypical parkinsonism, described by cardinal motor manifestations and the presence of cerebrovascular disease, particularly white matter hyperintensities (WMHs) in the basal ganglia and subcortical region. WMHs, in turn, are a recognised imaging spectrum of CSVD manifestations, and in relation to disrupted NGVU, also include enlarged perivascular spaces. Here, in this narrative review, we present and discuss on recent findings that argue for plausible clues between CSVD and VaP by focusing on aberrant multicellular dynamics of a unique integrated NGVU-a crossroad of the immune-vascular-nervous system-which may also extend fresher insights into the elusive interplay between cerebral microvasculature and neurodegeneration, and the potential therapeutic targets.

The Promise of the Zebrafish Model for Parkinson's Disease: Today's Science and Tomorrow's Treatment.

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 (Danio rerio) 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 Drosophila melanogaster and Caenorhabditis elegans. 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.

The effects of intravenous infusion of autologous mesenchymal stromal cells in patients with subacute middle cerebral artery infarct: a phase 2 randomized controlled trial on safety, tolerability and efficacy.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are characterized by paracrine and immunomodulatory functions capable of changing the microenvironment of damaged brain tissue toward a more regenerative and less inflammatory milieu. The authors conducted a phase 2, single-center, assessor-blinded randomized controlled trial to investigate the safety and efficacy of intravenous autologous bone marrow-derived MSCs (BMMSCs) in patients with subacute middle cerebral artery (MCA) infarct. METHODS: Patients aged 30-75 years who had severe ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 10-35) involving the MCA territory were recruited within 2 months of stroke onset. Using permuted block randomization, patients were assigned to receive 2 million BMMSCs per kilogram of body weight (treatment group) or standard medical care (control group). The primary outcomes were the NIHSS, modified Rankin Scale (mRS), Barthel Index (BI) and total infarct volume on brain magnetic resonance imaging (MRI) at 12 months. All outcome assessments were performed by blinded assessors. Per protocol, analyses were performed for between-group comparisons. RESULTS: Seventeen patients were recruited. Nine were assigned to the treatment group, and eight were controls. All patients were severely disabled following their MCA infarct (median mRS = 4.0 [4.0-5.0], BI = 5.0 [5.0-25.0], NIHSS = 16.0 [11.5-21.0]). The baseline infarct volume on the MRI was larger in the treatment group (median, 71.7 [30.5-101.7] mL versus 26.7 [12.9-75.3] mL, P = 0.10). There were no between-group differences in median NIHSS score (7.0 versus 6.0, P = 0.96), mRS (2.0 versus 3.0, P = 0.38) or BI (95.0 versus 67.5, P = 0.33) at 12 months. At 12 months, there was significant improvement in absolute change in median infarct volume, but not in total infarct volume, from baseline in the treatment group (P = 0.027). No treatment-related adverse effects occurred in the BMMSC group. CONCLUSIONS: Intravenous infusion of BMMSCs in patients with subacute MCA infarct was safe and well tolerated. Although there was no neurological recovery or functional outcome improvement at 12 months, there was improvement in absolute change in median infarct volume in the treatment group. Larger, well-designed studies are warranted to confirm this and the efficacy of BMMSCs in ischemic stroke.

Frequency of Cognitive Impairment Among Malaysian Elderly Patients Following First Ischaemic Stroke-A Case Control Study.

Background: Stroke is highly prevalent globally and is an important cause of cognitive impairment and dementia. Aims: We determined the frequency of post-stroke cognitive impairment (PSCI) at 1, 3, and 6 months among patients with first clinical ischemic stroke compared to risk and age-matched controls. Methods: This study involved 32 cases and 32 controls, and was conducted over 6 months. Cases were inpatients aged >60 with first clinical ischemic stroke. Controls were age-matched subjects without prior stroke. Montreal Cognitive Assessment (MoCA) was performed in all patients at 1, 3, and 6 month post stroke. A MoCA score of <26 was used for mild PSCI and <22 for moderate PSCI (post stroke dementia). Results: Post-stroke dementia was detected in 12 patients (37.5%) at 1st month, in 13 (40.6%) at 3rd month and 15 (48.4%) at 6th months. Mild PSCI was present in 7 patients (21.6%) at 1 month, 16 patients (50%) at 3 months, and 15 patients (48%) at 6 months. The odds ratio (OR) for post-stroke dementia was 3.2 (95%CI 0.98-10.68; p = 0.05) at 1 month; 3.69(95% CI 1.13-12.11; p = 0.031) at 3 months, and 4.88 (95% CI 1.49-15.99; p = 0.009) at 6 months. Years of education was an independent predictor for dementia (OR 0.60; p = 0.046). The OR for post-stroke dementia at 6th month was 7.23 with education level adjusted (95%CI 1.46-35.86, p = 0.015). Conclusion: The frequency of PSCI was high as early as 1 month after stroke. Stroke alone conferred a 7.2 times risk for post-stroke dementia compared to controls.

Frequency of Spinocerebellar Ataxia type 1, 2, 3,6 and 7 and clinical profile of Spinocerebellar Ataxia type 3 in Malaysia.

Spinocerebellar ataxias (SCA) are highly heterogenous group of neurodegenerative diseases causing progressive cerebellar dysfunction. We report the first description of relative frequencies of the common SCA mutations and of phenotypic characteristics of SCA3 patients among Malaysians. Pooled data from adult Malaysian patients who had undergone genetic testing for SCA 1,2,3,6 and 7 at UKM Medical Centre and Institute for Medical Research from 2017 to 2020 were analysed. Fifteen patients with SCA 3 had detailed clinical phenotype evaluation using Inventory for Non -Ataxia Signs (INAS) and Ataxia Severity evaluation using the Scale for Assessment and Rating of Ataxia (SARA). Out of 152 adults patients who were tested for common SCA mutations, 64(42.1%) patients were tested positive for either SCA 1,2,3,6 or 7. Of the 64 positive cases, 44 (68.9%) patients were diagnosed with SCA 3 followed by SCA 2 in 13(20.3%) patients and SCA 1 in 5 (7.8%) patients. Our findings suggest that Malay race had the highest frequency of SCA (n = 34, 50%), followed by the Chinese (n = 16, 23.5%) and approximately 60 (93.8%) SCA patients had first degree family history. In conclusion, SCA 3 is the commonest SCA in Malaysia, followed by SCA 2 and SCA 1. It is important to develop a proper registry of SCA patients to further understand the true prevalence and local impact of the disease in Malaysia.

MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease.

Among the neurodegenerative disorders, Parkinson's disease (PD) ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD). Despite similarities between the characteristics of EOPD and late onset PD (LODP), EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear. Recent findings in PD patients revealed that there were differences in the genetic profiles of PD patients compared to healthy controls, as well as between EOPD and LOPD patients. There were variants identified that correlated with the decline of cognitive and motor symptoms as well as non-motor symptoms in PD. There were also specific microRNAs that correlated with PD progression, and since microRNAs have been shown to be involved in the maintenance of neuronal development, mitochondrial dysfunction and oxidative stress, there is a strong possibility that these microRNAs can be potentially used to differentiate between subsets of PD patients. PD is mainly diagnosed at the late stage, when almost majority of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers for early detection of PD is important. Given that miRNAs are crucial in controlling the gene expression, these regulatory microRNAs and their target genes could be used as biomarkers for early diagnosis of PD. In this article, we discussed the genes involved and their regulatory miRNAs, regarding their roles in PD progression, based on the findings of significantly altered microRNAs in EOPD studies. We also discussed the potential of these miRNAs as molecular biomarkers for early diagnosis.