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3,900 results for “parkinsonism”
Restoration of striatal neuroprotective pathways by kinase inhibitor treatment of Parkinson’s linked-LRRK2 mutant mice
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Data from: Developmental exposure to the Parkinson’s disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice
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Developmental dieldrin exposure alters DNA methylation at genes related to dopaminergic neuron development and Parkinson’s disease in mouse midbrain
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Parkin regulates amino acid homeostasis at mitochondria-lysosome (M/L) contact sites in Parkinson’s disease
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<i>MSH3</i> is a genetic modifier of somatic repeat instability in X-linked dystonia parkinsonism
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The c-Abl inhibitor IkT-148009 therapeutically suppresses neurodegeneration in models of heritable and sporadic Parkinson’s Disease
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Data from: Blood NfL: a biomarker for disease severity and progression in Parkinson's disease
Objective: To examine whether plasma neurofilament light chain (NfL) levels were associated with motor and cognitive progression in Parkinson's disease (PD). Methods: This prospective follow-up study enrolled 178 participants, including 116 with PD, 22 with multiple system atrophy (MSA), and 40 healthy controls. We measured plasma NfL levels with electrochemiluminescence immunoassay. Patients with PD received evaluations of motor and cognition, at baseline and at a mean follow-up interval of 3 years. Changes in the unified Parkinson's disease rating scale (UPDRS) part III motor score and Mini-Mental State Examination (MMSE) score were used to assess motor and cognition progression. Results: Plasma fL levels were significantly higher in MSA than in PD and healthy groups (35.8±6.2 pg/ml, 17.6±2.8 pg/ml, and 10.6±2.3 pg/ml, respectively; P<0.001). In the PD group, NfL levels were significantly elevated in patients with advanced Hoehn-Yahr (H-Y) stage and patients with dementia (PDD) (P<0.001). NfL levels were modestly correlated with UPDRS part III scores (r=0.42, 95% CI: 0.46-0.56, P<0.001). After a mean follow-up of 3.4±1.2 years, a Cox regression analysis adjusted for age, sex, disease duration and baseline motor or cognitive status showed that higher baseline NfL levels were associated with higher risks for either motor or cognition progression (P=0.029 and P=0.015, respectively). Conclusions: Plasma NfL levels correlated with disease severity and progression in terms of both motor and cognitive functions in PD. Classification of evidence: This study provides Class III evidence that plasma NfL levels distinguish PD and MSA, and is a surrogate biomarker for PD progression.
Data associated with 'Metformin rescues Parkinson's disease phenotypes caused by hyperactive mitochondria'
<p>Metabolic dysfunction occurs in many age-related neurodegenerative diseases, yet its role in disease etiology remains poorly understood. We recently discovered a potential causal link between the branched-chain amino acid transferase, <i>BCAT-1,</i> and the neurodegenerative movement disorder, Parkinson's disease (PD). RNAi-mediated knockdown of <i>C. elegans bcat-1</i> recapitulates PD-like features, including progressive motor deficits and neurodegeneration with age, yet the underlying mechanisms have remained unknown. Using transcriptomic, metabolomic, and imaging approaches, we show here that <i>bcat-1 </i>knockdown increases mitochondrial respiration and induces oxidative damage in neurons through mTOR-independent mechanisms. Increased mitochondrial respiration, or 'mitochondrial hyperactivity,' is required for <i>bcat-1(RNAi)</i> neurotoxicity. Moreover, we show that post-disease onset administration of the type 2 diabetes medication, metformin, reduces mitochondrial respiration to control levels and significantly improves both motor function and neuronal viability. Together, our findings suggest that mitochondrial hyperactivity may be an early event in PD pathogenesis, and strategies aimed at reducing mitochondrial respiration may constitute a surprising new avenue for PD treatment.</p>
Data from: Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.
Data from: Effects of aging and idiopathic Parkinson's disease on tactile temporal order judgment
It is generally accepted that the basal ganglia play an important role in interval timing that requires the measurement of temporal durations. By contrast, it remains controversial whether the basal ganglia play an essential role in temporal order judgment (TOJ) of successive stimuli, a behavior that does not necessarily require the measurement of durations in time. To address this issue, we compared the effects of idiopathic Parkinson's disease (PD) on the TOJ of two successive taps delivered to each hand, with the arms uncrossed in one condition and crossed in another. In addition to age-matched elderly participants without PD (non-PD), we examined young healthy participants so that the effect of aging could serve as a control for evaluating the effects of PD. There was no significant difference between PD and non-PD participants in any parameter of TOJ under either arm posture, although reaction time was significantly longer in PD compared with non-PD participants. By contrast, the effect of aging was apparent in both conditions. With their arms uncrossed, the temporal resolution (the interstimulus interval that yielded 84% correct responses) in elderly participants was significantly worse compared with young participants. With their arms crossed, elderly participants made more errors at longer intervals (~1 s) than young participants, although both age groups showed similar judgment reversal at moderately short intervals (~200 ms). These results indicate that the basal ganglia and dopaminergic systems do not play essential roles in tactile TOJ involving both hands and that the effect of aging on TOJ is mostly independent of the dopaminergic systems.
Computerized analysis of hypomimia and hypokinetic dysarthria for improved diagnosis of Parkinson's disease
<p>Background and Objective: An aging society requires easy-to-use approaches for diagnosis and monitoring of neurodegenerative disorders, such as Parkinson's disease (PD), so that clinicians can effectively adjust a treatment policy and improve patients' quality of life. Current methods of PD diagnosis and monitoring usually require the patients to come to a hospital, where they undergo several neurological and neuropsychological examinations. These examinations are usually time consuming, expensive, and performed just a few times per year. Hence, this study explores the possibility of fusing computerized analysis of hypomimia and hypokinetic dysarthria (two motor symptoms manifested in the majority of PD patients) with the goal of proposing a new methodology of PD diagnosis that could be easily integrated into mHealth systems. Methods: We enrolled 73 PD patients and 46 age- and gender-matched healthy controls, who performed several speech/voice tasks while recorded by a microphone and a camera. Acoustic signals were parametrized in the fields of phonation, articulation and prosody. Video recordings of a face were analyzed in terms of facial landmarks movement. Both modalities were consequently modeled by the XGBoost algorithm. Results: The acoustic analysis enabled diagnosis of PD with 77% balanced accuracy, while in the case of the facial analysis, we observed 81% balanced accuracy. The fusion of both modalities increased the balanced accuracy to 83% (88% sensitivity and 78% specificity). The most informative speech exercise in the multimodality system turned out to be a tongue twister. Additionally, we identified muscle movements that are characteristic of hypomimia. Conclusions: The introduced methodology, which is based on the myriad of speech exercises likewise audio and video modality, allows for the detection of PD with an accuracy of up to 83%. The speech exercise - tongue twisters occurred to be the most valuable from the clinical point of view. Additionally, the clinical interpretation of the created models is illustrated. The presented computer-supported methodology could serve as an extra tool for neurologists in PD detection and the proposed potential solution of mHealth will facilitate the patient's and doctor's life</p>
Effectiveness of a multidisciplinary approach to prevent falls and gait impairment in patients with Parkinson's disease: A randomized, longitudinal clinical trial.
<p>This graph describes the <span>short and long-term effectiveness of a multidisciplinary telemedicine program in addition to in-office usual care in non-demented patients with PD at risk for falling.</span></p>
Parkinson and microbiome
<p>Parkinson's Disease (PD) is the second most prevalent neurodegenerative disorder, affecting approximately 1 million people or 1% of the U.S. population over the age of 60. It is marked by the gradual and progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Notably, intestinal inflammation and gastrointestinal abnormalities often precede the diagnosis by several years. PD is also characterized by the formation of Lewy bodies, whose primary structural component is α-synuclein (α-Syn). These α-Syn aggregates have been found in the gut of PD patients, suggesting a link between the gut microbiota and PD development. In this study, we explored the role of functional biomes, including the microbiome and mycobiome, in the manifestation of PD.</p>
Transcriptional analysis of peripheral memory T cells reveals Parkinson's disease-specific gene signatures--Fluorospot SFC
<p>Fluorospot SFC (combined IFNg, IL-5, and IL-10) data and corresponding HC-PD group IDs described in "Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures"</p>
Data from: Olfactory testing in Parkinson's disease & REM behavior disorder: a machine learning approach
<p><span><span><span><span><span><span><span><span><span><span><span><b>Objective: </b></span></span></span></span></span></span></span></span></span></span></span><span><span><span><span><span><span><span><span><span><span><span>We sought to identify an abbreviated test of impaired olfaction, amenable for use in busy clinical environments in prodromal (isolated REM sleep Behavior Disorder (iRBD)) and manifest Parkinson's.</span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Methods: </b></span></span></span></span></span></span></span></span></span></span></span><span><span><span><span><span><span><span><span><span><span><span>890 PD and 313 control participants in the Discovery cohort study underwent Sniffin' stick odour identification assessment. Random forests were initially trained to distinguish individuals with poor (functional anosmia/hyposmia) and good (normosmia/super-smeller) smell ability using all 16 Sniffin' sticks. Models were retrained using the top 3 sticks ranked by order of predictor importance. One randomly selected 3-stick model was tested in a second independent Parkinson's dataset (n=452) and in two iRBD datasets (Discovery n=241; Marburg n=37) before being compared to previously described abbreviated Sniffin' stick combinations.</span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Results: </b></span></span></span></span></span></span></span></span></span></span></span><span><span><span><span><span><span><span><span><span><span><span>In differentiating poor from good smell ability, the overall area under the curve (AUC) value associated with the top 3 sticks (Anise, Licorice and Banana) was 0.95 in the development dataset (sensitivity:90%, specificity:92%, PPV:92%, NPV:90%). Internal and external validation confirmed AUCs≥0.90. The combination of 3-stick model determined poor smell and an RBD screening questionnaire score of ≥5, separated iRBD from controls with a sensitivity, specificity, PPV and NPV of 65%, 100%, 100% and 30%. </span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Conclusions: </b></span></span></span></span></span></span></span></span></span></span></span><span><span><span><span><span><span><span><span><span><span><span>Our 3-Sniffin'-stick model holds potential utility as a brief screening test in the stratification of individuals with Parkinson's and iRBD according to olfactory dysfunction.</span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Classification of Evidence: </b></span></span></span></span></span></span></span></span></span></span></span><span><span><span><span><span><span><span><span><span><span><span>This study provides Class III evidence that a 3-Sniffin'-stick model distinguishes individuals with poor and good smell ability and can be used to screen for individuals with iRBD.</span></span></span></span></span></span></span></span></span></span></span></p>
Long-term effect of regular physical activity and exercise habits in patients with early parkinson disease
<p><span><span><span><span><span><span><span><span><span><span><span>Objective: Owing to the lack of long-term observations and/or comprehensive adjustment for confounding factors, reliable conclusions regarding long-term effects of exercise and regular physical activity in Parkinson's disease (PD) have yet to be drawn. Here, using data from the Parkinson's Progression Markers Initiative study that includes longitudinal and comprehensive evaluations of many clinical parameters, we examined the long-term effects of regular physical activity and exercise habits on the course of PD. </span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span>Methods: In this observational cohort study, we primarily used the multivariate linear mixed-effects models to analyze the interaction effects of their regular physical activity and moderate-to-vigorous exercise levels, measured through the Physical Activity Scale for the Elderly questionnaire, on the progression of clinical parameters, after adjusting for age, sex, levodopa-equivalent dose, and disease duration. We also calculated bootstrapping 95% confidence intervals (CIs), and conducted sensitivity analyses using the multiple imputation method and subgroup analyses using the propensity score matching to match for all baseline background factors. </span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span>Results: 237 early PD patients [median (interquartile range); age, 63.0 (56.0–70.0) years; Male, 69.2%; follow-up duration, 5.0 (4.0–6.0) years] were included. Regular physical activity and moderate-to-vigorous exercise levels at the baseline did not significantly affect the subsequent clinical progression of PD. However, average regular overall physical activity levels over time were significantly associated with slower deterioration of postural and gait stability [standardized fixed-effects coefficients of the interaction term (βinteraction) = -0.10 (95% CI, -0.14 to -0.06)], activities of daily living [βinteraction = 0.08 (95% CI, 0.04 to 0.12)], and processing speed [βinteraction = 0.05 (95% CI, 0.03 to 0.08)] in PD patients. Moderate-to-vigorous exercise levels were preferentially associated with slower decline of postural and gait stability [βinteraction = -0.09 (95% CI, -0.13 to -0.05)] and work-related activity levels were primarily associated with slower deterioration of processing speed [βinteraction = 0.07 (95% CI, 0.04 to 0.09)]. Multiple imputation and propensity score matching confirmed the robustness of our results. </span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span>Conclusions: In the long-term, the maintenance of high regular physical activity levels and exercise habits was robustly associated with better clinical course of PD, with each type of physical activity having different effects.</span></span></span></span></span></span></span></span></span></span></span></p>
Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson's disease
<p>Raw data for the manuscript "Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson’s disease"</p>
Unaltered T cell responses to common antigens in individuals with Parkinson's disease--AIM Assay FCS (1.2/3)
<p>FCS files pertaining to the AIM analysis described and included in "Unaltered T cell responses to common antigens in individuals with Parkinson's disease". Part 1.2/3 of dataset, data key can be found in within 3/3 upload.</p>
Unaltered T cell responses to common antigens in individuals with Parkinson's disease--AIM Assay FCS Data (1/3)
<p>FCS files pertaining to the AIM analysis described and included in "Unaltered T cell responses to common antigens in individuals with Parkinson's disease". Part 1/3 of dataset, data key can be found in within 3/3 upload.</p>
Unaltered T cell responses to common antigens in individuals with Parkinson's disease--AIM Assay FCS (2/3)
<p>FCS files pertaining to the AIM analysis described and included in "Unaltered T cell responses to common antigens in individuals with Parkinson's disease". Part 2/3 of dataset, data key can be found in within 3/3 upload.</p>
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
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The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
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