Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease

Journal of Parkinson s Disease, Journal Year: 2014, Volume and Issue: 4(3), P. 337 - 344

Published: July 28, 2014

Background:Data from an open label randomised controlled trial have suggested possible advantages on both motor and non-motor measures in patients with Parkinson's disease following 12 months exposure to exenatide.Objective: Continued follow up of these same was performed investigate whether persisted the prolonged absence this medication.Methods: All participants label, exenatide as a treatment for disease, were invited further assessment at UCL Institute Neurology.This visit included all 20 individuals who had previously completed twelve 10ug bd 24 acted controls.Motor severity PD compared after overnight withdrawal conventional medication using blinded video MDS-UPDRS, together several tests.This thus their original baseline visit, i.e. cessation exenatide.Results: Compared control group patients, exposed advantage 5.6 points (95% CI, 2.2-9.0;p = 0.002) rating MDS-UPDRS part 3 subscale.There also difference 5.3 points; 9.3-1.4;p 0.006) between 2 groups Mattis Dementia Rating scale.Conclusions: While data must still not be interpreted evidence neuroprotection, they nevertheless provide strong encouragement study drug potential modifying agent disease.

Language: Английский

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Parkinson's disease subtypes: lost in translation?

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2012, Volume and Issue: 84(4), P. 409 - 415

Published: Sept. 5, 2012

Like many neurodegenerative disorders, Parkinson9s disease (PD) is clinically highly heterogeneous. A number of studies have proposed and defined subtypes PD based on clinical features that tend to cluster together. These present an opportunity refine aetiology, course treatment responsiveness in PD, as variability must represent underlying biological or pathophysiological differences between individuals. In this paper, we review what been identified the validation they undergone. We then discuss could tell us about how incorporated into progression treatment. Finally, with knowledge very little research, make recommendations for should be used some practical address lack translation.

Language: Английский

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Parkinson’s Disease is Predominantly a Genetic Disease

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(3), P. 467 - 482

Published: March 26, 2024

The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene Contursi kindred 1997 indisputably confirmed genetic cause subset Parkinson’s disease (PD) patients. Currently, variants one seven established PD genes or strongest known risk factor gene, GBA1, are identified ∼15% patients unselected for age at onset and family history. In this Debate article, we highlight multiple avenues research that suggest an important - some cases even predominant role genetics aetiology, including familial clustering, high rates monogenic selected populations, complete penetrance with certain forms. At first sight, steep increase prevalence exceeding other neurodegenerative diseases may argue against etiology. Notably, principal contribution is conferred by LRRK2 GBA1 and, both cases, characterized overall late age-related penetrance. addition, polygenic plays considerable PD. However, it likely that, majority patients, complex interplay aging, genetic, environmental, epigenetic factors leads to development.

Language: Английский

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Depression and anxiety related subtypes in Parkinson's disease

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2011, Volume and Issue: 82(7), P. 803 - 809

Published: Jan. 8, 2011

Background Depression and anxiety are common in Parkinson's disease (PD) although clinically important remain poorly understood managed. To date, research has tended to treat depression as distinct phenomena. There is growing evidence for heterogeneity PD the motor cognitive domains, with implications pathophysiology outcome. Similar may exist domain of anxiety. Objective identify main related subtype(s) their associated demographic clinical features. Methods A sample 513 patients received a detailed assessment symptomatology. Latent Class Analysis (LCA) was used putative subtypes. Results LCA identified four classes, two interpretable ‘anxiety related’: one alone (22.0%) other coexisting prominent depressive symptoms (8.6%). third subtype (9%) showed profile only without significant The final class (60.4%) low probability affective symptoms. validity classes supported by patterns association variables. Conclusion manifest phenotypes, ‘anxious–depressed’ ‘depressed’. However, further large proportion can have relatively isolated Further study these phenotypes differences aetiologically factors focus on developing more targeted effective treatment.

Language: Английский

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Developing and validating Parkinson’s disease subtypes and their motor and cognitive progression

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2018, Volume and Issue: 89(12), P. 1279 - 1287

Published: July 25, 2018

Objectives To use a data-driven approach to determine the existence and natural history of subtypes Parkinson’s disease (PD) using two large independent cohorts patients newly diagnosed with this condition. Methods 1601 944 idiopathic PD, from Tracking Discovery cohorts, respectively, were evaluated in motor, cognitive non-motor domains at baseline assessment. Patients recently entry (within 3.5 years diagnosis) followed up every 18 months. We used factor analysis by k-means cluster analysis, while prognosis was measured random slope intercept models. Results identified four clusters: (1)  fast motor progression symmetrical disease, poor olfaction, cognition postural hypotension; (2) mild intermediate progression; (3) severe , psychological well-being sleep an (4) slow tremor-dominant, unilateral disease. Clusters moderately substantially stable across (kappa 0.58). Cluster 1 had fastest 3.2 (95% CI 2.8 3.6) UPDRS III points per year 4 slowest 0.6 (0.1–1.1). In Parkinson’s, 2 largest response levodopa 36.3% lowest 28.8%. Conclusions have found novel clusters that replicated well early PD associated rates. This has potential implications for better understanding pathophysiology relevance patient stratification future clinical trials.

Language: Английский

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Early-onset vs. Late-onset Parkinson’s disease: A Clinical-pathological Study

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, Journal Year: 2015, Volume and Issue: 43(1), P. 113 - 119

Published: July 20, 2015

Abstract Background: Several studies have compared early-onset Parkinson disease (EOPD) and late-onset (LOPD) but most are not based on autopsy confirmed cases. Methods: We clinical pharmacological profiles, time to reach irreversible Hoehn Yahr (H&Y) Stage 3 levodopa motor complications in EOPD LOPD Results: At first clinic visit cases were younger had longer duration they died at a age (all p<0.0001). Anti-Parkinsonian drug use, including levodopa, was significantly delayed EOPD. Lifetime use of amantadine (p<0.05) dopamine agonists (p<0.01) higher While lifetime similar the two groups, used for period by (p< 0.0001). cumulative incidence dyskinesias (p<0.01), wearing-off on-off (p<0.01). However, dyskinesia onset groups. The threshold much H&Y stage profile from Conclusions: Our observations indicate that progression PD is slower suggest pre-clinical interval this group longer. These findings can be case selection trials pathogenesis PD.

Language: Английский

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Novel Approaches Targeting in α-Synuclein for Parkinson's Disease: Current Progress and Future Directions for the Disease-Modifying Therapies

Brain Disorders, Journal Year: 2024, Volume and Issue: unknown, P. 100163 - 100163

Published: Sept. 1, 2024

Language: Английский

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Behavioral screening defines three molecular Parkinsonism subgroups in Drosophila

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 27, 2024

Abstract Parkinsonism is defined by motor dysfunction, but the specific upstream molecular causes of these clinical symptoms can vary widely. We hypothesize that converge onto a limited number core cellular pathways. To investigate this, we created new collection 24 genetically very well-controlled animal models familial forms parkinsonism. Using unbiased behavioral screening and machine learning identified three clusters mutants on (1) mitochondrial function; (2) retromer/vesicle trafficking; (3) proteostasis/autophagy. Genes within each cluster have similar genetic interaction profile compounds target pathways ameliorate dopaminergic neuron dysfunction in cluster-specific manner. This suggests parkinsonism be stratified into broad functional groups our findings pave way for targeted biomarker discovery drug development.

Language: Английский

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Reproducibility of data-driven Parkinson's disease subtypes for clinical research

Parkinsonism & Related Disorders, Journal Year: 2018, Volume and Issue: 56, P. 102 - 106

Published: July 20, 2018

Language: Английский

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Contributions of the Basal Ganglia to Temporal Processing: Evidence from Parkinson’s Disease

Timing & Time Perception, Journal Year: 2013, Volume and Issue: 2(1), P. 87 - 127

Published: Nov. 18, 2013

The motor and perceptual timing deficits documented in patients with Parkinson’s disease (PD) have heavily influenced the theory that basal ganglia play an important role temporal processing. This review is a systematic exploration of findings from behavioural neuroimaging studies PD. In particular, we consider influence variety task factors patient heterogeneity explaining mixed results. We also effect dysfunction on non-temporal cognitive contribute to successful timing. Although there convincing evidence PD are critical timing, further work needed characterize precise contribution this complex structure

Language: Английский

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