Motor Symptoms
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2021 ◽  
Dilan Athauda ◽  
James Evans ◽  
Anna Wernick ◽  
Gurvir Virdi ◽  
Minee Liane-Choi ◽  

Importance: Type 2 diabetes (T2DM) is an established risk factor for developing Parkinson's disease (PD) but its effect on disease progression is not well understood. Objective: To examine the effects of co-morbid T2DM on Parkinson's disease progression and quality of life. Design: We analysed data from the Tracking Parkinson's study, a large multi-centre prospective study in the UK. Participants: The study included 1930 adults with recent onset PD, recruited between February 2012 and May 2014, and followed up regularly thereafter. Exposure: A diagnosis of pre-existing T2DM was based on self-report at baseline. After controlling for confounders, an evaluation of how T2DM affects PD was performed by comparing symptom severity scores; and analyses using multivariable mixed models was used to determine the effects of T2DM on Parkinson's disease progression. Main Outcomes and Measures: The impact of T2DM on Parkinsons disease severity was derived from scores collected using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Questionnaire for impulsive-compulsive disorders in PD (QUIP), Leeds Anxiety and Depression Scale (LADS), and Schwab and England ADL scale. Results: We identified 167 (8.7%) patients with PD and T2DM (PD+T2DM) and 1763 (91.3%) with PD without T2DM (PD). Patients with T2DM had more severe motor symptoms, as assessed by MDS-UPDS III 25.8 (0.9) vs 22.5 (0.3) p=0.002, had significantly faster motor symptom progression over time (p=0.012), and T2DM was an independent predictor for the development of substantial gait impairment (HR 1.55, CI 1.07-2.23, p=0.020). Patients were more likely to have loss of independence (OR 2.08, CI 1.34-3.25, p=0.001); and depression (OR 1.62, CI 1.10-2.39, p=0.015), and developed worsening mood (p=0.041) over time compared to the PD group. T2DM was also an independent predictor for the development mild cognitive impairment (HR 1.7, CI 1.24-2.51, p=0.002) over time Conclusions and relevance: T2DM is associated with faster disease progression in PD, highlighting an interaction between these two diseases. As it is a potentially modifiable, metabolic state, with multiple peripheral and central targets for intervention, it may represent a target for ameliorating parkinsonian symptoms, and progression to disability and dementia.

2021 ◽  
pp. 1-12
Anna Sauerbier ◽  
Pia Bachon ◽  
Leire Ambrosio ◽  
Philipp A. Loehrer ◽  
Alexandra Rizos ◽  

Background: The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. Objective: To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. Methods: In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. Results: 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p <  0.01), indicating a moderate convergent validity. The SLTS-7 significantly increased with higher non-motor symptoms burden levels (p = 0.002). Conclusion: Life satisfaction in PD covers three specific aspects, namely physical, psycho-social, and treatment satisfaction. The new SLTS-7 is a valid, reliable, and easy-to-use tool to assess satisfaction with life and treatment in patients with PD screened for advanced therapies. Longitudinal studies analyzing the effect of advanced PD treatment on life and treatment satisfaction are warranted.

2021 ◽  
Vol 13 ◽  
Ye Tian ◽  
Mingyang He ◽  
Lina Pan ◽  
Xin Yuan ◽  
Min Xiong ◽  

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. However, its cellular and molecular mechanisms still wrap in the mist. This is partially caused by the absence of appropriate animal models mimicking sporadic PD that constitutes the majority of cases. Previously, we reported that a cysteine protease, asparagine endopeptidase (AEP), is activated in an age-dependent manner, and cleaves α-synuclein in the brain of sporadic PD patients. The AEP-derived α-synuclein 1-103 fragment is required for the pathogenesis of PD. Thus, we designed and characterized a novel transgenic mouse line expressing α-synuclein 1-103 (designated N103 mice). This model shows an abundant accumulation of pathological α-synuclein in the central nervous system, loss of dopaminergic neurons in the substantia nigra, and progressive striatal synaptic degeneration. The N103 mice also manifest age-dependent PD-like behavioral impairments. Notably, the mice show weight loss and constipation, which are the common non-motor symptoms in PD. The RNA-sequencing analysis found that the transcriptomics pattern was extensively altered in N103 mice. In conclusion, the N103 mouse line, as a brand-new tool, might provide new insights into PD research.

2021 ◽  
Vol 11 (1) ◽  
Catherine Viel ◽  
Jennifer Clarke ◽  
Can Kayatekin ◽  
Amy M. Richards ◽  
Ming Sum R. Chiang ◽  

AbstractMutations in GBA, the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), represent the greatest genetic risk factor for developing synucleinopathies including Parkinson’s disease (PD). Additionally, PD patients harboring a mutant GBA allele present with an earlier disease onset and an accelerated disease progression of both motor and non-motor symptoms. Preclinical studies in mouse models of synucleinopathy suggest that modulation of the sphingolipid metabolism pathway via inhibition of glucosylceramide synthase (GCS) using a CNS-penetrant small molecule may be a potential treatment for synucleinopathies. Here, we aim to alleviate the lipid storage burden by inhibiting the de novo synthesis of the primary glycosphingolipid substrate of GCase, glucosylceramide (GlcCer). We have previously shown that systemic GCS inhibition reduced GlcCer and glucosylsphingosine (GlcSph) accumulation, slowed α-synuclein buildup in the hippocampus, and improved cognitive deficits. Here, we studied the efficacy of a brain-penetrant clinical candidate GCS inhibitor, venglustat, in mouse models of GBA-related synucleinopathy, including a heterozygous Gba mouse model which more closely replicates the typical GBA-PD patient genotype. Collectively, these data support the rationale for modulation of GCase-related sphingolipid metabolism as a therapeutic strategy for treating GBA-related synucleinopathies.

2022 ◽  
Vol 12 (1) ◽  
pp. 1-15
Sanjana Tomer ◽  
Ketna Khanna ◽  
Sapna Gambhir ◽  
Mohit Gambhir

Parkinson disease (PD) is a neurological disorder where the dopaminergic neurons experience deterioration. It is caused from the death of the dopamine neurons present in the substantia nigra i.e., the mid part of the brain. The symptoms of this disease emerge slowly, the onset of the earlier stages shows some non-motor symptoms and with time motor symptoms can also be gauged. Parkinson is incurable but can be treated to improve the condition of the sufferer. No definite method for diagnosing PD has been concluded yet. However, researchers have suggested their own framework out of which MRI gave better results and is also a non-invasive method. In this study, the MRI images are used for extracting the features. For performing the feature extraction techniques Gray Level Co-occurrence Matrix and Principal Component Analysis are performed and are analysed. Feature extraction reduces the dimensionality of data. It aims to reduce the feature of data by generating new features from the original one.

2021 ◽  
Muzaffer Arikan ◽  
Zeynep Yildiz ◽  
Tugce Kahraman Demir ◽  
Nesrin H. Yilmaz ◽  
Aysu Sen ◽  

Introduction: Cognitive impairment (CI) is among the most common non-motor symptoms of Parkinson's disease (PD) with substantially negative impact on patient management and outcome. The development and progression of CI exhibits high interindividual variability which requires better diagnostic and monitoring strategies. PD patients often display sweating disorders resulting from autonomic dysfunction which has been associated with CI. As the axillary microbiota is known to change with humidity level and sweat composition, we hypothesized that axillary microbiota of PD patients shifts in association with CI progression thus can be used as proxy for classification of CI stages in PD. Methods: We compared the axillary microbiota compositions of 103 PD patients (55 PD patients with dementia (PDD) and 48 PD patients with mild cognitive impairment (PD-MCI)) and 26 cognitively normal healthy controls (HC). Results: We found that axillary microbiota profiles differentiate HC, PD-MCI and PDD groups based on differential ranking analysis and detected an increasing trend in the log ratio of Corynebacterium to Anaerococcus in progression from HC to PDD. In addition, phylogenetic factorization revealed that the depletion of Anaerococcus, Peptoniphilus and W5053 genera is associated with PD-MCI and PDD. Moreover, functional predictions suggested significant increase of myo-inositol degradation, ergothioneine biosynthesis, propionate biosynthesis, menaquinone biosynthesis, and the proportion of aerobic bacteria and biofilm formation capacity in parallel to CI. Conclusion: Our results suggest that alterations in axillary microbiota are associated with CI in PD. Thus, axillary microbiota holds potential to be exploited as a non-invasive biomarker in the development of novel strategies.

2021 ◽  
Vol 19 (3) ◽  
pp. 411-432
Do Manh Hung ◽  
Nguyen Hai Ha ◽  
Nguyen Dang Ton

      Parkinson disease (PD) is the second-most common and complex neurodegenerative disorders in humans, characterized by motor symptoms such as tremor, rigidity, bradykinesia, and non-motor symptoms such as insomnia, constipation, anxiety, depression and fatigue. Up to now, the diagnosis of PD has been mainly based on clinical symptoms with motor features being the mainstay and this limits the possibility of early detection. PD is usually diagnosis after the sixth decade of life, however about 5–10% of patients who develop the disease before the age of 50 are early-onset PD. The rapid development of genetic studies and their application may induce the early diagnosis of PD in the near future, especially for the early-onset PD. A few mechanisms have been implicated in PD pathogenesis, with α-synuclein aggregation central to the development of the disease. Multiple other processes are thought to be involved, with several studies suggesting that abnormal protein clearance, mitochondrial dysfunction, and neuroinflammation play a role in the onset and progression of PD. There are many PD patients in Vietnam, however, the studies are mainly based on clinical symtom descriptions. Given the aging of the population, the prevalence of PD is to increase dramatically, which would lead to increased urgency for the need to identify improved methods in diagnosis and treatment this disease.

2021 ◽  
Vol 13 ◽  
Bianca Guglietti ◽  
David Hobbs ◽  
Lyndsey E. Collins-Praino

Cognitive dysfunction, primarily involving impairments in executive function, visuospatial function and memory, is one of the most common non-motor symptoms of Parkinson’s disease (PD). Currently, the only pharmacological treatments available for the treatment of cognitive dysfunction in PD provide variable benefit, making the search for potential non-pharmacological therapies to improve cognitive function of significant interest. One such therapeutic strategy may be cognitive training (CT), which involves the repetition of standardized tasks with the aim of improving specific aspects of cognition. Several studies have examined the effects of CT in individuals with PD and have shown benefits in a variety of cognitive domains, but the widespread use of CT in these individuals may be limited by motor impairments and other concerns in study design. Here, we discuss the current state of the literature on the use of CT for PD and propose recommendations for future implementation. We also explore the potential use of more recent integrative, adaptive and assistive technologies, such as virtual reality, which may optimize the delivery of CT in PD.

2021 ◽  
Yoon-Sang Oh ◽  
Sang-Won Yoo ◽  
Chul Hyoung Lyoo ◽  
Joong-Seok Kim

Abstract Drug-induced parkinsonism (DIP) is caused by a dopamine receptor blockade and is a major cause of misleading diagnosis of Parkinson’s disease (PD). Striatal dopamine activity has been investigated widely in DIP; however, most studies with dopamine transporter imaging have focused on the clinical characteristics and prognosis. This study investigated differences in striatal subregional monoamine availability among patients with DIP, normal controls, and patients with early PD. Thirty-five DIP patients, the same number of age-matched PD patients, and 46 healthy controls were selected for this study. Parkinsonian motor status was examined. Brain magnetic resonance imaging and positron emission tomography with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane were performed, and the regional standardized uptake values were analyzed with a volume-of-interest template and compared among the groups. Females were more predominant in the DIP group than in the PD group. Parkinsonian motor symptoms were similar in the DIP and PD groups. Monoamine availability in the thalamus of the DIP group was lower than that of the normal controls and similar to that of the PD group. In other subregions (putamen, globus pallidus, and ventral striatum), monoamine availability in the DIP group and normal controls did not differ and was higher than that in the PD group. These findings suggest that low monoamine availability in the thalamus could be an imaging biomarker of DIP.

Takashi Sugiyama ◽  
Nobuyuki Ishii ◽  
Yuka Ebihara ◽  
Kazutaka Shiomi ◽  
Hitoshi Mochizuki

As a result of population growth and the development of tube wells, humans’ exposure to arsenic has increased over the past few decades. The natural course of organ damage secondary to arsenic exposure is not yet well understood. In Toroku, Japan, an arsenic mine was intermittently operated from 1920 to 1962, and residents were exposed to high concentrations of arsenic. In this paper, we analyzed 190 consecutive residents for whom detailed records of neurological symptoms and findings were obtained from 1974 to 2005. All participants were interviewed regarding the presence of general, skin, hearing, respiratory, and neurological symptoms. Neurological symptoms were classified into extremity numbness or pain, constipation, dyshidrosis, sensory loss, and muscle atrophy. Superficial and vibratory sensation was also evaluated. More than 80% of participants experienced extremity numbness, and numbness was the most common neurological symptom. Numbness was associated with superficial sensory disturbance, and was correlated with the subsequent development of other neurological symptoms, including autonomic and motor symptoms. No previous studies have investigated the natural course of chronic arsenic intoxication; thus, these data serve as a guide for detecting early symptoms due to arsenic exposure.

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