Precompetitive data sharing as a catalyst to address unmet needs in Parkinson's disease

Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson's disease.

Machine learning for large-scale wearable sensor data in Parkinson disease:concepts, promises, pitfalls, and futures

For the treatment and monitoring of Parkinson's disease (PD) to be scientific, a key requirement is that measurement of disease stages and severity is quantitative, reliable, and repeatable. The last 50 years in PD research have been dominated by qualitative, subjective ratings obtained by human interpretation of the presentation of disease signs and symptoms at clinical visits. More recently, “wearable,” sensor-based, quantitative, objective, and easy-to-use systems for quantifying PD signs for large numbers of participants over extended durations have been developed. This technology has the potential to significantly improve both clinical diagnosis and management in PD and the conduct of clinical studies. However, the large-scale, high-dimensional character of the data captured by these wearable sensors requires sophisticated signal processing and machine-learning algorithms to transform it into scientifically and clinically meaningful information. Such algorithms that “learn” from data have shown remarkable success in making accurate predictions for complex problems in which human skill has been required to date, but they are challenging to evaluate and apply without a basic understanding of the underlying logic on which they are based. This article contains a nontechnical tutorial review of relevant machine-learning algorithms, also describing their limitations and how these can be overcome. It discusses implications of this technology and a practical road map for realizing the full potential of this technology in PD research and practice. © 2016 International Parkinson and Movement Disorder Society.

Technology in Parkinson's disease:challenges and opportunities

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

Parkinson-kóros betegek betegségteher felmérése Magyarországon

Szerte Európában az öregedő társadalom problémájával nézünk szembe. Ezzel függ össze a növekvő Parkinson-esetszám (Magyarországon megközelítőleg 20 000 beteg él ezzel a betegséggel), és az egyre nagyobb igény az idősödéssel összefüggő egészségügyi kiadásokra. Egyre fontosabb szerephez jut a költségtudatos egészségügyi gondoskodás. A betegségteher felmérések ezt igyekszenek alátámasztani. Keresztmetszeti kérdőíves vizsgálatot végeztünk a SE Neurológiai Klinika Parkinson-kórral élő betegein, életminőséget (EQ-5D és PDQ-39 kérdőívekkel) és a betegség költségeit (indirekt és direkt) vizsgálva. Az eredmények szerint a betegséggel összefüggő költségek jelentősek, 3 509 310 Ft/beteg/év, és a betegség jelentős életminőség csökkenést okoz. Tanulmányunkban a 2008 őszén elkezdett kutatást szeretnénk bemutatni, ismertetni a módszertant és az eredményeket, összevetve nemzetközi adatokkal.

Modelo animal da Doença de Parkinson baseado na expressão de alfa - sinucleína: caracterização comportamental, eletrofisiológica e avaliação dos efei tos da estimulação da medula espinhal

Parkinson disease (PD) is associated with motor symptoms and dopaminergic cell loss in the nigrostriatal pathway. Alpha-synuclein is the major component of the Lewy bodies, the biological hallmarks of disease, and has been associated with familial cases of PD. Recently, the spinal cord stimulation (SCS) showed to be effective to alleviate the Parkinson symptoms in animal models and human patients. In this project, we characterized the motor and electrophysiological effects of alpha-synuclein overexpression in the substantia nigra of rats. We further investigated the effects of spinal electrical stimulation, AMPT and L-dopa administration in this model. Method: Sprague-Dawley rats were injected with empty viral vector or the vector carrying the gene for alpha-synuclein in the substantia nigra, and were tested weekly for 10 weeks in the open field and cylinder tests. A separated group of animals implanted with bilateral electrode arrays in the motor cortex and the striatum were recorded in the open field, during the SCS sessions and the pharmacological experiments. Results: Alpha-synuclein expression resulted in motor asymmetry, observed as the reduction in use of contralateral forepaw in the cylinder test. Animals showed an increase of local field potential activity in beta band three and four weeks after the virus injection, that was not evident after the 5th week. AMPT resulted in a sever parkinsonian state, with reduction in the locomotor activity and significant peak of oscillatory activity in cortex and striatum. SCS was effective to alleviate the motor asymmetry at long term, but did not reduce the corticostriatal low frequency oscillations observed 24 hs after the AMPT administration. These oscillations were attenuated by L-dopa that, even as SCS, was not effective to restore the locomotor activity during the severe dopaminergic depletion period. Discussion: The alpha-synuclein model reproduces the motor impairment and the progressive neurodegenerative process of PD. We demonstrated, by the first time, that this model also presents the increase in low frequency oscillatory activity in the corticostriatal circuit, compatible with parkinsonian condition; and that SCS has a therapeutic effect on motor symptom of this model.

Relação do polimorfismo BDNF val66met e níveis periféricos de BDNF com a doença de Parkinson e sua sintomatologia

Neurodegenerative diseases are frequently studied due to the increasing number of cases associated with the populational ageing and to the impact on the conditions on the quality of life. Parkinson’s disease (DP) is the second most frequent neurodegenerative disease. Despite the fact that its etiology is not completely understood, it is known that DP is caused by environmental and genetic factors. Thus, the investigation of etiologic factors and mechanisms responsible for the changes that lead to DP may help early diagnostic and prevention. A possible association between DP and the common polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies with contrasting results. For this reason, the aim of this study is to investigate if the BDNF Val66Met polymorphism is related to susceptibility to DP in a cohort of Brazilian patients. Additionaly, we verify if the presence of the polymorphism implies in alterations in the BDNF whole blood concentrations, as well as variations in symptomatology. The sample comprised Brazilian patients accompanied by the neurology service of the Onofre Lopes University Hospital (HUOL) and healthy controls (CTRL). The motor aspects of DP were evaluated by Hoehn e Yahr Scale (HY), Unified Parkinson’s Disease Rating Scale (UPDRS) and Schwab & England Scale (SE). For the evaluation of non-motor symptoms were used the following instruments: Frontal Assessment Battery (BAF), Mini-Mental State Examination (MEEM), Beck Depression Inventory (IDB) and the Beck Anxiety Inventory (IAB). Blood samples were collected for BDNF Val66Met polymorphism genotyping and BDNF whole blood measurement. As expected, DP patients performed worse in motor, cognitive and emotional battery of questionnaires. Alleles distribution between DP and CTRL was not significantly different, but the A/G genotype was significantly associated with a protector factor for DP. In contrast, the G/G genotype was significantly associated with depression and anxiety development in DP patients. However, BDNF concentrations were not different between genotypes or groups. This is the first study of genetic association of this polymorphism with DP in Brazilian subjects and the first one that associate A/G genotype with protection against DP.

Estudio longitudinal del rendimiento neuropsicológico, neuropsiquiátrico y motor en la enfermedad de Parkinson

La enfermedad de Parkinson (EP) es una enfermedad progresiva, crónica e incapacitante cuyos síntomas principales son el temblor de reposo, la rigidez y la bradicinesia, apareciendo en el transcurso del tiempo la inestabilidad postural. Las alteraciones cognitivas y del estado de ánimo son otra de las características de esta enfermedad, pudiendo constituir una de sus complicaciones más incapacitantes. Ni el deterioro cognitivo leve (DCL) ni la demencia (D-EP) son fáciles de definir ni de evaluar. Algunos autores describen el DCL como una fase premórbida de la demencia (Pigott et al, 2015) aunque no todos los pacientes evolucionan a D-EP. La prevalencia de la D-EP es de 20-40% (Aarsland, Anderson et al, 2001), siendo algunos de los factores de riesgo la edad avanzada al diagnóstico, los síntomas motores más graves, sobre todo los relacionados con el trastorno de la marcha y la inestabilidad postural, el deterioro cognitivo leve, la depresión, el déficit temprano en fluidez verbal, la aparición de alucinaciones o la escasa respuesta al tratamiento con levodopa (Emre, 2003). El perfil de demencia en la EP es de tipo frontosubcortical, con déficits en las funciones atencionales y ejecutivas, mnésicas, visoespaciales, la fluidez verbal y las praxias...

A systematic review of loss of independence in Parkinson's disease

Acknowledgments We thank Dr Daan Velseboer for providing additional unpublished data for this review. We thank Dr Lorna Aucott for her comments on a draft of this paper. We are grateful for funding for this study from the Chief Scientist Office of the Scottish Government (Clinical Academic Fellowship CAF/12/05) and from Parkinson’s UK (Grant Number G-1302).

A systematic review of loss of independence in Parkinson's disease

Acknowledgments We thank Dr Daan Velseboer for providing additional unpublished data for this review. We thank Dr Lorna Aucott for her comments on a draft of this paper. We are grateful for funding for this study from the Chief Scientist Office of the Scottish Government (Clinical Academic Fellowship CAF/12/05) and from Parkinson’s UK (Grant Number G-1302).

Risk of fracture amongst patients with Parkinson's disease and other forms of parkinsonism

Acknowledgements We thank all the participants who took part, the research fellows (Kate Taylor, Robert Caslake, David McGhee, Angus Macleod) and nurses (Clare Harris, Joanna Gordon, Anne Hayman, Hazel Forbes) who helped assess the participants, and the study secretaries (Susan Kilpatrick, Pam Rebecca) and data management team (Katie Wilde, David Ritchie). The PINE study was funded by the BMA Doris Hillier award, Parkinson's UK, the RS McDonald Trust, NHS Grampian Endowments, SPRING and the BUPA Foundation. None of the funders had any influence in the study design, the collection, analysis and interpretation of the data, the writing of the report or the decision to submit the article for publication.

Mémoire de travail et mémoire procédurale dans la maladie de Parkinson : évaluation et entraînement

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

La réalité virtuelle pour initier et contrôler la démarche chez des patients atteints de la maladie de Parkinson

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire de travail et mémoire procédurale dans la maladie de Parkinson : évaluation et entraînement

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

La réalité virtuelle pour initier et contrôler la démarche chez des patients atteints de la maladie de Parkinson

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Visual memory errors in Parkinson's disease patient with visual hallucinations

The occurrences of visual hallucinations seem to be more prevalent in low light and hallucinators tend to be more prone to false positive type errors in memory tasks. Here we investigated whether the richness of stimuli does indeed affect recognition differently in hallucinating and nonhallucinating participants, and if so whether this difference extends to identifying spatial context. We compared 36 Parkinson's disease (PD) patients with visual hallucinations, 32 Parkinson's patients without hallucinations, and 36 age-matched controls, on a visual memory task where color and black and white pictures were presented at different locations. Participants had to recognize the pictures among distracters along with the location of the stimulus. Findings revealed clear differences in performance between the groups. Both PD groups had impaired recognition compared to the controls, but those with hallucinations were significantly more impaired on black and white than on color stimuli. In addition, the group with hallucinations was significantly impaired compared to the other two groups on spatial memory. We suggest that not only do PD patients have poorer recognition of pictorial stimuli than controls, those who present with visual hallucinations appear to be more heavily reliant on bottom up sensory input and impaired on spatial ability.