scholarly journals Semantic Memory and Lexical Availability in Parkinson’s Disease: A Statistical Learning Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Juan F. Cardona ◽  
Johan S. Grisales-Cardenas ◽  
Catalina Trujillo-Llano ◽  
Jesús A. Diazgranados ◽  
Hugo F. Urquina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Semantic Memory ◽  
Classification Accuracy ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Semantic Fluency ◽  
Semantic Categories ◽  
Semantic Fields ◽  
Living Things

Parkinson’s disease (PD) is a neurodegenerative disorder that causes a progressive impairment in motor and cognitive functions. Although semantic fluency deficits have been described in PD, more specific semantic memory (SM) and lexical availability (LA) domains have not been previously addressed. Here, we aimed to characterize the cognitive performance of PD patients in a set of SM and LA measures and determine the smallest set of neuropsychological (lexical, semantic, or executive) variables that most accurately classify groups. Thirty early-stage non-demented PD patients (age 35–75, 10 females) and thirty healthy controls (age 36–76, 12 females) were assessed via general cognitive, SM [three subtests of the CaGi battery including living (i.e., elephant) and non-living things (i.e., fork)], and LA (eliciting words from 10 semantic categories related to everyday life) measures. Results showed that PD patients performed lower than controls in two SM global scores (picture naming and naming in response to an oral description). This impairment was particularly pronounced in the non-living things subscale. Also, the number of words in the LA measure was inferior in PD patients than controls, in both larger and smaller semantic fields, showing a more inadequate recall strategy. Notably, the classification algorithms indicated that the SM task had high classification accuracy. In particular, the denomination of non-living things had a classification accuracy of ∼80%. These results suggest that frontostriatal deterioration in PD leads to search strategy deficits in SF and the potential disruption in semantic categorization. These findings are consistent with the embodied view of cognition.

scholarly journals Plasma-borne indicators of inflammasome activity in Parkinson’s disease patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Faith L. Anderson ◽  
Katharine M. von Herrmann ◽  
Angeline S. Andrew ◽  
Yuliya I. Kuras ◽  
Alison L. Young ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Inflammasome Activation ◽  
Membrane Pore ◽  
Related Proteins ◽  
Inflammasome Activity

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss but no diagnosis of PD identified elevated expression of inflammasome-related proteins and activation-related “speck” formation in degenerating mesencephalic tissues compared with controls. Based on previous reports of circulating inflammasome proteins in patients suffering from heritable syndromes caused by hyper-activation of the NLRP3 inflammasome, we evaluated PD patient plasma for evidence of inflammasome activity. Multiple circulating inflammasome proteins were detected almost exclusively in extracellular vesicles indicative of ongoing inflammasome activation and pyroptosis. Analysis of plasma obtained from a multi-center cohort identified elevated plasma-borne NLRP3 associated with PD status. Our findings are consistent with others indicating inflammasome activity in neurodegenerative disorders. Findings suggest mesencephalic inflammasome protein expression as a histopathologic marker of early-stage nigral degeneration and suggest plasma-borne inflammasome-related proteins as a potentially useful class of biomarkers for patient stratification and the detection and monitoring of inflammation in PD.

Olfactory Function and Diffusion Tensor Imaging as Markers of Mild Cognitive Impairment in Early Stages of Parkinson's Disease

2021 ◽  
pp. 155005942110582
Author(s):  
Sophie A. Stewart ◽  
Laura Pimer ◽  
John D. Fisk ◽  
Benjamin Rusak ◽  
Ron A. Leslie ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Neurodegenerative Disorder ◽  
Diffusion Tensor ◽  
Early Stage ◽  
White Matter Integrity

Parkinson's disease (PD) is a neurodegenerative disorder that is typified by motor signs and symptoms but can also lead to significant cognitive impairment and dementia Parkinson's Disease Dementia (PDD). While dementia is considered a nonmotor feature of PD that typically occurs later, individuals with PD may experience mild cognitive impairment (PD-MCI) earlier in the disease course. Olfactory deficit (OD) is considered another nonmotor symptom of PD and often presents even before the motor signs and diagnosis of PD. We examined potential links among cognitive impairment, olfactory functioning, and white matter integrity of olfactory brain regions in persons with early-stage PD. Cognitive tests were used to established groups with PD-MCI and with normal cognition (PD-NC). Olfactory functioning was examined using the University of Pennsylvania Smell Identification Test (UPSIT) while the white matter integrity of the anterior olfactory structures (AOS) was examined using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) analysis. Those with PD-MCI demonstrated poorer olfactory functioning and abnormalities based on all DTI parameters in the AOS, relative to PD-NC individuals. OD and microstructural changes in the AOS of individuals with PD may serve as additional biological markers of PD-MCI.

scholarly journals Prediction of Parkinson’s Disease at Early Stage using Big Data Analytics

2020 ◽  
Vol 9 (4) ◽  
pp. 2453-2459
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Big Data ◽  
Data Analytics ◽  
Clinical Medicine ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Big Data Analytics ◽  
Analytical Techniques ◽  
Predictive Methods

Due to technological improvements in healthcare industry and clinical medicine, it requires to adapt new software techniques and tools to predict, diagnose and analyze disease patterns for making decisions in the early stage of disease. Parkinson’s disease is a neurodegenerative disorder. The PD damage the motor skills and may create speech problem and also affect the decision making process. Many people suffers with PD all over the world from many years. Day by day, the PD data has been increased, so the existing data mining predictive methods and tools does not give accurate results early for making decisions by doctors to save and increase the patient life period. Early PD symptoms can be detected by Big Data Analytics and proper medicine will be provided at the right time. In this paper, we are doing survey of predictive methods, Big Data Analytical techniques and also earlier researchers results presented.

scholarly journals Verbal fluency deficits in Parkinson's disease: A meta-analysis

2004 ◽  
Vol 10 (4) ◽  
pp. 608-622 ◽  
Author(s):  
JULIE D. HENRY ◽  
JOHN R. CRAWFORD
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Semantic Memory ◽  
Verbal Fluency ◽  
Meta Analysis ◽  
Relative Magnitude ◽  
Semantic Fluency ◽  
Confrontation Naming ◽  
Cognitive Speed ◽  
Differential Deficit

A meta-analysis of 68 studies with a total of 4644 participants was conducted to investigate the sensitivity of tests of verbal fluency to the presence of Parkinson's disease (PD) relative to healthy controls. Both phonemic and semantic fluency were moderately impaired but neither deficit qualified as a differential deficit relative to verbal intelligence or psychomotor speed. However, PD patients were significantly more impaired on semantic relative to phonemic fluency (rs = .37vs..33, respectively), and confrontation naming, a test of semantic memory that imposes only minimal demands upon cognitive speed and effortful retrieval, was associated with a deficit that was of a comparable magnitude to the deficits upon each of these types of fluency. Thus, the disorder appears to be associated with particular problems with semantic memory. Tests that impose heavy demands upon switching may also be disproportionately affected. Demented and non-demented PD patients differ quantitatively but not qualitatively in terms of the relative prominence of deficits on tests of phonemic and semantic fluency. However, patients with dementia of the Alzheimer's type and demented PD patients can be differentiated from one another by the relative magnitude of deficits upon these two measures. (JINS, 2004,10, 608–622.)

scholarly journals Functional and Cognitive Improvement After an Intensive Inpatient Multidisciplinary Rehabilitation Program in Mild to Severe Parkinson's Disease: A Retrospective and Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Mario Meloni ◽  
Francesca Lea Saibene ◽  
Sonia Di Tella ◽  
Monica Di Cesare ◽  
Francesca Borgnis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Observational Study ◽  
Functional Disability ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Rehabilitation Program ◽  
Semantic Fluency ◽  
Multidisciplinary Rehabilitation ◽  
Cognitive Improvement

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor (resting tremor, rigidity, bradykinesia, postural instability, and gait disturbances) and nonmotor symptoms (cognitive, neuropsychiatric, and autonomic problems). In recent years, several studies demonstrated that neurorehabilitation therapy is an effective treatment in addition to pharmacological personalized interventions in persons with PD (PwPD). The main aim of this study was to explore the short-term changes in functional, cognitive, and geriatric domains after a multidimensional rehabilitation program in PwPD (as primary condition) in mild–moderate (M-Ms) to severe (Ss) stages. Our second aim was to compare the effects of multidimensional rehabilitation in M-Ms versus Ss of PD. Twenty-four PwPD in M-Ms to Ss [age (mean ± SD) = 76.25 ± 9.42 years; male/female = 10/14; Hoehn and Yahr (median; IQR) = 4.00; 1.75] were included in a retrospective, observational study. Motor, cognitive, functional, and neuropsychiatric aspects were collected in admission (T0) and in discharge (T1). PwPD were involved in a person-tailored (to individual's needs), inpatient, intensive (5–7 days per week), multidisciplinary (combining cognitive, physical, occupational, and speech therapies), comprehensive, and rehabilitative program. According to Movement Disorders Society Unified Parkinson's Disease Rating Scale III cutoff, PwPD were classified in M-Ms or Ss (M-Ms ≤59; Ss >59); 87.50% of our sample reported significant reduction of functional disability at Barthel Index (p < 0.001). A significant improvement in Token test (p = 0.021), semantic fluency (p = 0.036), Rey's Figure-Copy (p < 0.001), and Raven's Colored Progressive Matrices (p = 0.004) was observed. The pain intensity perception (p < 0.001) and the risk of developing pressure ulcers (p < 0.001) as assessed, respectively, by the Numeric Rating Scale and by the Norton Scale were improved. With regard to the second aim, in M-Ms group, we found a positive correlation between the number of neuromotor sessions and the change in functional disability and language comprehension; in the Ss group, on the other hand, despite a higher number of hospitalization days, the total number of completed sessions was positively associated with the change in visuoconstructional abilities. Our findings suggest that an intensive, inpatient, and multidisciplinary rehabilitation program may improve functional abilities, some strategic cognitive functions, and geriatric aspects in PwPD with mild–moderate motor impairment.

scholarly journals Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

2021 ◽  
Vol 13 ◽  
Author(s):  
Upasana Ganguly ◽  
Sukhpal Singh ◽  
Soumya Pal ◽  
Suvarna Prasad ◽  
Bimal K. Agrawal ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Movement Disorders ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Motor Impairment ◽  
The Elderly ◽  
Alpha Synuclein ◽  
Cross Sectional ◽  
Peripheral Tissues

Parkinson’s disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

scholarly journals Autophagic- and Lysosomal-Related Biomarkers for Parkinson’s Disease: Lights and Shadows

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1317 ◽  
Author(s):  
Helena Xicoy ◽  
Núria Peñuelas ◽  
Miquel Vila ◽  
Ariadna Laguna
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Biomarker Discovery ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Functional Studies ◽  
Functional Consequences ◽  
Gba Mutations ◽  
Lysosomal Proteins

Parkinson’s disease (PD) is a neurodegenerative disorder that currently affects 1% of the population over the age of 60 years, for which no disease-modifying treatments exist. This lack of effective treatments is related to the advanced stage of neurodegeneration existing at the time of diagnosis. Thus, the identification of early stage biomarkers is crucial. Biomarker discovery is often guided by the underlying molecular mechanisms leading to the pathology. One of the central pathways deregulated during PD, supported both by genetic and functional studies, is the autophagy-lysosomal pathway. Hence, this review presents different studies on the expression and activity of autophagic and lysosomal proteins, and their functional consequences, performed in peripheral human biospecimens. Although most biomarkers are inconsistent between studies, some of them, namely HSC70 levels in sporadic PD patients, and cathepsin D levels and glucocerebrosidase activity in PD patients carrying GBA mutations, seem to be consistent. Hence, evidence exists that the impairment of the autophagy-lysosomal pathway underlying PD pathophysiology can be detected in peripheral biosamples and further tested as potential biomarkers. However, longitudinal, stratified, and standardized analyses are needed to confirm their clinical validity and utility.

scholarly journals Biomarkers and the Role of α-Synuclein in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Tingting Du ◽  
Le Wang ◽  
Weijin Liu ◽  
Guanyu Zhu ◽  
Yingchuan Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Lewy Bodies ◽  
Review Article ◽  
Tissue Imaging ◽  
Peripheral Tissues

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the presence of α-synuclein (α-Syn)-rich Lewy bodies (LBs) and the preferential loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta (SNpc). However, the widespread involvement of other central nervous systems (CNS) structures and peripheral tissues is now widely documented. The onset of the molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD, so early diagnosis of PD and adequate tracking of disease progression could significantly improve outcomes for patients. Because the clinical diagnosis of PD is challenging, misdiagnosis is common, which highlights the need for disease-specific and early-stage biomarkers. This review article aims to summarize useful biomarkers for the diagnosis of PD, as well as the biomarkers used to monitor disease progression. This review article describes the role of α-Syn in PD and how it could potentially be used as a biomarker for PD. Also, preclinical and clinical investigations encompassing genetics, immunology, fluid and tissue, imaging, as well as neurophysiology biomarkers are discussed. Knowledge of the novel biomarkers for preclinical detection and clinical evaluation will contribute to a deeper understanding of the disease mechanism, which should more effectively guide clinical applications.

scholarly journals Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson’s disease mouse model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Robin Ji ◽  
Morgan Smith ◽  
Yusuke Niimi ◽  
Maria E. Karakatsani ◽  
Maria F. Murillo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Neurotrophic Factor ◽  
Focused Ultrasound ◽  
Neurodegenerative Disorder ◽  
Control Function ◽  
Early Stage ◽  
Brain Derived Neurotrophic Factor ◽  
Nigrostriatal Pathway

AbstractFocused ultrasound-enhanced intranasal (IN + FUS) delivery is a noninvasive approach that utilizes the olfactory pathway to administer pharmacological agents directly to the brain, allowing for a more homogenous distribution in targeted locations compared to IN delivery alone. However, whether such a strategy has therapeutic values, especially in neurodegenerative disorders such as Parkinson’s disease (PD), remains to be established. Herein, we evaluated whether the expression of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine catalysis, could be enhanced by IN + FUS delivery of brain-derived neurotrophic factor (BDNF) in a toxin-based PD mouse model. Mice were put on the subacute dosing regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), producing bilateral degeneration of the nigrostriatal pathway consistent with early-stage PD. MPTP mice then received BDNF intranasally followed by multiple unilateral FUS-induced blood-brain barrier (BBB) openings in the left basal ganglia for three consecutive weeks. Subsequently, mice were survived for two months and were evaluated morphologically and behaviorally to determine the integrity of their nigrostriatal dopaminergic pathways. Mice receiving IN + FUS had significantly increased TH immunoreactivity in the treated hemisphere compared to the untreated hemisphere while mice receiving only FUS-induced BBB opening or no treatment at all did not show any differences. Additionally, behavioral changes were only observed in the IN + FUS treated mice, indicating improved motor control function in the treated hemisphere. These findings demonstrate the robustness of the method and potential of IN + FUS for the delivery of bioactive factors for treatment of neurodegenerative disorder.

scholarly journals The Endotoxin-Induced Neuroinflammation Model of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-25 ◽  
Author(s):  
Kemal Ugur Tufekci ◽  
Sermin Genc ◽  
Kursad Genc
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Experimental Studies ◽  
Bacterial Endotoxin ◽  
Dopaminergic Neurodegeneration ◽  
Nigrostriatal Dopaminergic Neurodegeneration ◽  
Peripheral Immune Cells

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. Although the exact cause of the dopaminergic neurodegeneration remains elusive, recent postmortem and experimental studies have revealed an essential role for neuroinflammation that is initiated and driven by activated microglial and infiltrated peripheral immune cells and their neurotoxic products (such as proinflammatory cytokines, reactive oxygen species, and nitric oxide) in the pathogenesis of PD. A bacterial endotoxin-based experimental model of PD has been established, representing a purely inflammation-driven animal model for the induction of nigrostriatal dopaminergic neurodegeneration. This model, by itself or together with genetic and toxin-based animal models, provides an important tool to delineate the precise mechanisms of neuroinflammation-mediated dopaminergic neuron loss. Here, we review the characteristics of this model and the contribution of neuroinflammatory processes, induced by thein vivoadministration of bacterial endotoxin, to neurodegeneration. Furthermore, we summarize the recent experimental therapeutic strategies targeting endotoxin-induced neuroinflammation to elicit neuroprotection in the nigrostriatal dopaminergic system. The potential of the endotoxin-based PD model in the development of an early-stage specific diagnostic biomarker is also emphasized.

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