The impact of clinical scales in Parkinson’s disease: a systematic review

Abstract Background Parkinson’s disease is one of the non-curable diseases and occurs by the prominent loss of neurotransmitter (dopamine) in substantia nigra pars compacta (SNpc). The main cause behind this is not yet identified and even its diagnosis is very intricate phase due to non-identified onset symptoms. Despite the fact that PD has been extensively researched over the decades, and various algorithms and strategies for early recognition and avoiding misdiagnosis have been published. The objective of this article is to focus on the current scenario and to explore the involvement of various clinical diagnostic scales in the detection of PD. Method An exhaustive literature review is conducted to synthesize the earlier work in this area, and the articles were searched using different keywords like Parkinson disease, motor/non-motor, treatment, diagnosis, scales, PPMI, etc., in all repositories such as Google scholar, Scopus, Elsevier, PubMed and many more. From the year 2017 to 2021, a total of 451 publications were scanned, but only 24 studies were chosen for a review process. Findings Mostly as clinical tools, UPDRS and HY scales are commonly used and even there are many other scales which can be helpful in detection of symptoms such as depression, anxiety, sleepiness, apathy, smell, anhedonia, fatigue, pain, etc., that affect the QoL of pateint. The recognition of non-motor manifests is typically very difficult than motor signs. Conclusion This study can give the beneficial research paths at an early stage diagnosis by focusing on frequent inspection of daily activities, interactions, and routine, which may also give a plethora of information on status changes, directing self-reformation, and clinical therapy.

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Effects of deep brain stimulation on sleep-wake disturbances in patients with Parkinson's disease: A narrative review

Current Neuropharmacology ◽

10.2174/1570159x19666210215115718 ◽

2021 ◽

Vol 19 ◽

Author(s):

Yu Jin Jung ◽

Han-Joon Kim ◽

Sun Ha Paek ◽

Beomseok Jeon

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Early Stage ◽

Motor Symptoms ◽

Specific Effects ◽

The Impact ◽

Non Motor Symptoms ◽

Deep Brain

: Sleep-wake disturbances (SWD) are one of the most common non-motor symptoms in Parkinson's disease (PD) and can appear in the early stage even before the onset of motor symptoms. Deep brain stimulation (DBS) is an established treatment for the motor symptoms in patients with advanced PD. However, the effect of DBS on SWD and its specific mechanisms are not widely understood and remain controversial. In addition to the circuit-mediated direct effect, DBS may improve SWD by an indirect effect such as the resolution of nocturnal motor complications and a reduction of dopaminergic medication. Here, the authors review the recent literatures regarding the impact of DBS on SWD in patients with PD. Furthermore, the selection of the DBS targets and the specific effects of applying DBS to each target on SWD in PD are also discussed.

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Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21103459 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3459 ◽

Cited By ~ 2

Author(s):

Sandra Barata-Antunes ◽

Fábio G. Teixeira ◽

Bárbara Mendes-Pinheiro ◽

Ana V. Domingues ◽

Helena Vilaça-Faria ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Animal Welfare ◽

Neurodegenerative Disorder ◽

Negative Impact ◽

Substantia Nigra Pars Compacta ◽

Nigrostriatal Pathway ◽

Aged Rats ◽

Age Related ◽

The Impact

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

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Astrocytic Oxidative/Nitrosative Stress Contributes to Parkinson’s Disease Pathogenesis: The Dual Role of Reactive Astrocytes

Antioxidants ◽

10.3390/antiox8080265 ◽

2019 ◽

Vol 8 (8) ◽

pp. 265 ◽

Cited By ~ 17

Author(s):

Asha Rizor ◽

Edward Pajarillo ◽

James Johnson ◽

Michael Aschner ◽

Eunsook Lee

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Nitrosative Stress ◽

Critical Role ◽

Substantia Nigra Pars Compacta ◽

Environmental Toxicants ◽

Oxidative And Nitrosative Stress ◽

Reactive Astrogliosis ◽

The Impact

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide; it is characterized by dopaminergic neurodegeneration in the substantia nigra pars compacta, but its etiology is not fully understood. Astrocytes, a class of glial cells in the central nervous system (CNS), provide critical structural and metabolic support to neurons, but growing evidence reveals that astrocytic oxidative and nitrosative stress contributes to PD pathogenesis. As astrocytes play a critical role in the production of antioxidants and the detoxification of reactive oxygen and nitrogen species (ROS/RNS), astrocytic oxidative/nitrosative stress has emerged as a critical mediator of the etiology of PD. Cellular stress and inflammation induce reactive astrogliosis, which initiates the production of astrocytic ROS/RNS and may lead to oxidative/nitrosative stress and PD pathogenesis. Although the cause of aberrant reactive astrogliosis is unknown, gene mutations and environmental toxicants may also contribute to astrocytic oxidative/nitrosative stress. In this review, we briefly discuss the physiological functions of astrocytes and the role of astrocytic oxidative/nitrosative stress in PD pathogenesis. Additionally, we examine the impact of PD-related genes such as α-synuclein, protein deglycase DJ-1( DJ-1), Parkin, and PTEN-induced kinase 1 (PINK1) on astrocytic function, and highlight the impact of environmental toxicants, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, manganese, and paraquat, on astrocytic oxidative/nitrosative stress in experimental models.

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Possible selves and illness: A comparison of individuals with Parkinson's disease, early-stage Alzheimer's disease, and healthy older adults

International Journal of Behavioral Development ◽

10.1080/01650250143000526 ◽

2003 ◽

Vol 27 (1) ◽

pp. 1-11 ◽

Cited By ~ 29

Author(s):

Leslie D. Frazier ◽

Victoria Cotrell ◽

Karen Hooker

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Possible Selves ◽

Early Stage ◽

Healthy Older Adults ◽

Patient Groups ◽

The Impact

This study examined how future self-representations are affected by two different chronic illnesses, one focused on cognitive losses, early-stage Alzheimer's disease (AD), and one focused on physical losses, Parkinson's disease (PD). The impact of illness on possible selves (perceptions of self in the future) was made salient by a comparison with healthy older adults in order to better understand developmental issues in later life. Findings show that although there were no differences in the total number of domains reported by the groups, specific domains were reported differently by patient groups and all domains were likely to become infused with illness. As expected, patient groups had less self-efficacy and lower outcome expectancies for their future selves, and PD patients reported less distance from their feared selves. Although these findings are intuitive, this is the first empirical effort to document the impact of illness on older adults' self-representations. Group differences are explained in terms of disease context, and the importance of possible selves and self-regulatory functions as therapeutic mechanisms for adaptation to illness are emphasised.

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Nonmotor Symptoms in Early- and Advanced-Stage Parkinson’s Disease Patients on Dopaminergic Therapy: How Do They Correlate with Quality of Life?

ISRN Neurology ◽

10.1155/2014/587302 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 12

Author(s):

Peter Valkovic ◽

Jan Harsany ◽

Marta Hanakova ◽

Jana Martinkova ◽

Jan Benetin

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Advanced Stage ◽

Nonmotor Symptoms ◽

Related Quality ◽

Attention Memory ◽

The Impact

To determine the impact of nonmotor symptoms (NMS) on health-related quality of life (HRQoL) we examined 100 Parkinson’s disease (PD) patients on dopaminergic medications. An “early-stage” (ES) and an “advanced-stage” (AS) groups were formed. HRQoL was established by the questionnaire PDQ-8, number of NMS by NMSQuest, and severity and frequency of NMS by the assessment scale NMSS. The total NMS averaged 11.3 (ES=9.6, AS=12.8). The NMSS domain correlation profiles for ES and AS did not fundamentally differ; however, the domains attention/memory and mood/apathy correlated moderately to strongly with HRQoL in ES, while the sleep/fatigue domain correlated moderately with HRQoL in AS. Weakly correlating domains were sleep/fatigue in ES and cardiovascular, attention/memory, and mood/apathy domains in AS. In view of these findings we strongly recommend systematic, active screening and therapy for neuropsychiatric disorders (mood, cognitive and sleep disorders, and fatigue) at the initial diagnosis and throughout the entire course of PD.

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Delayed orthostatic hypotension in Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00181-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Sang-Won Yoo ◽

Joong-Seok Kim ◽

Ji-Yeon Yoo ◽

Eunkyeong Yun ◽

Uicheul Yoon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Orthostatic Hypotension ◽

Disease Severity ◽

Cortical Thickness ◽

Early Stage ◽

Brain Magnetic Resonance Imaging ◽

Clinical Scales ◽

Drug Naïve

AbstractOrthostatic hypotension (OH) is relatively common in the early stage of Parkinson’s disease (PD). It is divided into delayed OH and classical OH. Classical OH in PD has been investigated widely, however, the clinical implications of delayed OH in PD have seldom been studied. The purpose of this study is to characterize delayed OH in PD. A total of 285 patients with early drug-naïve PD were enrolled and divided into three groups according to orthostatic change: no-OH, delayed OH, and classical OH. The disease severity in terms of motor, non-motor, and cognitive functions was assessed. The cortical thickness of 82 patients was analyzed with brain magnetic resonance imaging. The differences among groups and linear tendency in the order of no-OH, delayed OH, and classical OH were investigated. Seventy-seven patients were re-evaluated. Initial and follow-up evaluations were explored to discern any temporal effects of orthostasis on disease severity. Sixty-four (22.5%) patients were defined as having delayed OH and 117 (41.1%) had classical OH. Between-group comparisons revealed that classical OH had the worst outcomes in motor, non-motor, cognitive, and cortical thickness, compared to the other groups. No-OH and delayed OH did not differ significantly. Linear trends across the pre-ordered OH subtypes found that clinical parameters worsened along with the orthostatic challenge. Clinical scales deteriorated and the linear gradient was maintained during the follow-up period. This study suggests that delayed OH is a mild form of classical OH in PD. PD with delayed OH has milder disease severity and progression.

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Pronounced α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum and amygdala

10.1101/2020.03.26.006189 ◽

2020 ◽

Author(s):

Johannes Burtscher ◽

Jean-Christophe Copin ◽

Carmen Sandi ◽

Hilal A. Lashuel

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Mitochondrial Dysfunction ◽

Mitochondrial Respiration ◽

Early Stage ◽

Relevant Literature ◽

Brain Regions ◽

Substantia Nigra Pars Compacta ◽

Ros Generation

AbstractIncreasing evidence suggests that crosstalk between α-synuclein pathology formation and mitochondrial dysfunctions plays a central role in the pathogenesis of Parkinson’s disease and related synucleinopathies. While mitochondrial dysfunction is a well-studied phenomenon in the substantia nigra, which is selectively vulnerable in Parkinson’s disease and some models thereof, less information is available in other brain regions that are also affected by synuclein pathology.Therefore, we sought to test the hypothesis that early α-synuclein pathology causes mitochondrial dysfunction, and that this effect might be exacerbated in conditions of increased vulnerability of affected brain regions, such as the amygdala.We combined a model of intracerebral α-synuclein pathology seeding with chronic glucocorticoid treatment modelling non-motor symptoms of Parkinson’s disease and affecting amygdala physiology. We measured mitochondrial respiration, ROS generation and protein abundance as well as α-synuclein pathology in male mice.Chronic corticosterone administration induced mitochondrial hyperactivity in the amygdala. Although injection of α-synuclein preformed fibrils into the striatum resulted in pronounced α-synuclein pathology in both striatum and amygdala, mitochondrial respiration in these brain regions was altered in neither chronic corticosterone nor control conditions.Our results suggest that early stage α-synuclein pathology does not influence mitochondrial respiration in the striatum and amygdala, even in corticosterone-induced respirational hyperactivity. We discuss our findings in light of relevant literature, warn of a potential publication bias and encourage scientist to report their negative results in the frame of this model.Significance statementWe provide evidence that early stage synucleinopathy by itself or in combination with exogenous corticosterone induced amygdala hyperactivity did not compromise mitochondrial respiration in the striatum and amygdala in one of the most commonly used models of synucleinopathies. These results may explain, why this model in the hands of many research groups does not elicit pronounced Parkinson’s disease like symptoms in the absence of mitochondrial dysfunction in brain regions strongly affected by synuclein pathology and involved in non-motor (amygdala) and motor (striatum) symptoms. Our findings call for rigorous investigation of the short- and long-term effects of α-synuclein pathology on mitochondrial function/dysfunction in this model, in particular in brain regions strongly affected by neurodegeneration such as the substantia nigra pars compacta.

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X-Vectors: New Quantitative Biomarkers for Early Parkinson's Disease Detection From Speech

Frontiers in Neuroinformatics ◽

10.3389/fninf.2021.578369 ◽

2021 ◽

Vol 15 ◽

Author(s):

Laetitia Jeancolas ◽

Dijana Petrovska-Delacrétaz ◽

Graziella Mangone ◽

Badr-Eddine Benkelfat ◽

Jean-Christophe Corvol ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Speaker Recognition ◽

Early Stage ◽

Gaussian Mixture ◽

Gender Effect ◽

Training Data ◽

Voice Analysis ◽

High Quality ◽

The Impact

Many articles have used voice analysis to detect Parkinson's disease (PD), but few have focused on the early stages of the disease and the gender effect. In this article, we have adapted the latest speaker recognition system, called x-vectors, in order to detect PD at an early stage using voice analysis. X-vectors are embeddings extracted from Deep Neural Networks (DNNs), which provide robust speaker representations and improve speaker recognition when large amounts of training data are used. Our goal was to assess whether, in the context of early PD detection, this technique would outperform the more standard classifier MFCC-GMM (Mel-Frequency Cepstral Coefficients—Gaussian Mixture Model) and, if so, under which conditions. We recorded 221 French speakers (recently diagnosed PD subjects and healthy controls) with a high-quality microphone and via the telephone network. Men and women were analyzed separately in order to have more precise models and to assess a possible gender effect. Several experimental and methodological aspects were tested in order to analyze their impacts on classification performance. We assessed the impact of the audio segment durations, data augmentation, type of dataset used for the neural network training, kind of speech tasks, and back-end analyses. X-vectors technique provided better classification performances than MFCC-GMM for the text-independent tasks, and seemed to be particularly suited for the early detection of PD in women (7–15% improvement). This result was observed for both recording types (high-quality microphone and telephone).

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Iron Chelation For Diseases Of Regional Siderosis

Blood ◽

10.1182/blood.v122.21.3435.3435 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3435-3435

Author(s):

Zvi Ioav Cabantchik ◽

Caroline Moreau ◽

David Devos

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Iron Overload ◽

Early Stage ◽

Hematological Parameters ◽

Friedreich Ataxia ◽

Iron Chelation ◽

Substantia Nigra Pars Compacta ◽

Traditional Role ◽

Entire Study

Abstract The traditional role of iron chelation therapy has been the reduction of body iron burden via chelation of excess metal from organs and fluids and its excretion via biliary-fecal and/or urinary routes. While that approach is applicable to systemic iron overload, as seen in various forms of hemosiderosis, it might not be suited for treating disorders of iron maldistribution that are characterized by discrete islands of siderosis that appear in a context background of normal or subnormal iron levels (as in sideroblastic anemias, cardiosiderosis in Friedreich ataxia-FRDA and neurosiderosis in Parkinson’s disease-PD). With the aim of clearing siderotic regions from labile (toxic) metal without interfering with essential local functions or with hematological iron-associated indices, we assessed here a conservative modality of iron chelation based on redeploying tissue chelated metal to physiological transferrin ( Sohn et al Blood 111:1690-9). As test redeployment agent we used deferiprone (DFP), a chelator with clinical proven record for correcting cardiac siderosis in systemic iron overload and in FRDA regional siderosis and for neuroprotection in a translational model of regional (brain) siderosis (that simulate key features of PD)( Moreau et al Am. J. Hematol. 2013;88:E5-E243). As part of a placebo-controlled randomized clinical trial of DFP in early stage PD patients (n=40) already stabilized with dopamine/dopaminergic regimens, we assessed whether a up to 18 month treatment (DFP 30 mg/kg/d in 2 daily syrup servings of Ferriprox) that significantly decreased substantia nigra-pars compacta siderosis (by T2* MRI) and showed neuro-functional benefits (UPDRS score), affected adversely hematological parameters. With the exception of 2 neutropenia patients that were withdrawn early in the trial (and resolved spontaneously) all others on DFP maintained steady plasma iron (80-115 ug/L), Tf- Sat (17-33%) hemoglobin levels (13.8-14.4 g/dL) and hematocrit (40-42 %) throughout the entire study, with just traces of daily sideruria but with serum ferritin that significantly dropped from 95±35 ng/ml to 30 ± 10 ng/ml during the first 12 months but not thereafter. We conclude that to the extent that iron chelation might have beneficial effects for treating neurodegenerative disorders that have a component of neurosiderosis, the modality of the DFP-based therapy provides a paradigm for treating regional siderosis without affecting hematological parameters. Supported by PHRC grants from the French Ministry of Research and the Adelina and Massimo DellaPergola Chair, HUJI, Jerusalem, Israel Disclosures: Cabantchik: Aferrix: Consultancy; Apopharma: invited speaker, invited speaker Other; Novartis: Speakers Bureau. Off Label Use: Deferiprone for Parkinson's Disease.

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Towards physiologically relevant human pluripotent stem cell (hPSC) models of Parkinson’s disease

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02326-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Elena Coccia ◽

Tim Ahfeldt

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Pluripotent Stem Cells ◽

Vascular System ◽

Threshold Model ◽

Embryonic Stem ◽

Model Systems ◽

Substantia Nigra Pars Compacta ◽

The Impact

AbstractThe derivation of human embryonic stem cells followed by the discovery of induced pluripotent stem cells and leaps in genome editing approaches have continuously fueled enthusiasm for the development of new models of neurodegenerative diseases such as Parkinson’s disease (PD). PD is characterized by the relative selective loss of dopaminergic neurons (DNs) in specific areas of substantia nigra pars compacta (SNpc). While degeneration in late stages can be widespread, there is stereotypic early degeneration of these uniquely vulnerable neurons. Various causes of selective vulnerability have been investigated but much remains unclear. Most studies have sought to identify cell autonomous properties of the most vulnerable neurons. However, recent findings from genetic studies and model systems have added to our understanding of non-cell autonomous contributions including regional-specific neuro-immune interactions with astrocytes, resident or damage-activated microglia, neuro-glia cell metabolic interactions, involvement of endothelial cells, and damage to the vascular system. All of these contribute to specific vulnerability and, along with aging and environmental factors, might be integrated in a complex stressor-threshold model of neurodegeneration. In this forward-looking review, we synthesize recent advances in the field of PD modeling using human pluripotent stem cells, with an emphasis on organoid and complex co-culture models of the nigrostriatal niche, with emerging CRISPR applications to edit or perturb expression of causal PD genes and associated risk factors, such as GBA, to understand the impact of these genes on relevant phenotypes.

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