| Data | Helena Denis | Dr. Francesca Cicchetti | CHUQ | Les vésicules extracellulaires dérivées d'érythrocyte: biomarqueurs de la maladie de Parkinson | La maladie de Parkinson (MP) est une maladie neurodégénérative qui résulte de la mort lente et progressive de certains groupes de neurones dans le cerveau. Comme la zone du cerveau atteinte par la maladie joue un rôle important dans le contrôle de nos mouvements, les personnes atteintes souffrent de rigidité, de lenteur, de tremblements mais aussi, à l’occasion, de problèmes cognitifs. À l'échelle mondiale, la maladie est diagnostiquée chez plus de 300 000 personnes chaque année. A l’heure actuelle, aucun traitement n’est disponible pour guérir la maladie et le diagnostic demeure complexe. Nous avons donc pour objectif de développer un outil de diagnostic de la MP grâce à un prélèvement sanguin. Mon projet porte plus spécifiquement sur l’étude et la caractérisation des vésicules extracellulaires (VE) présentes dans le plasma d’individus souffrant de la MP et leurs contrôles appariés. En effet, toutes les cellules vivantes, y compris les cellules sanguines, ont la capacité de libérer des VE composées de protéines, de lipides et de composantes cellulaires. Au cours d’une étude pilote que nous avons réalisé, les échantillons d’une cohorte de 60 patients et 37 contrôles ont été récoltés et différentes sous-populations de VE quantifiées dans le plasma. Ces analyses ont révélé des différences significatives entre la quantité de VE dérivées d’érythrocyte entre patients et contrôles, laquelle corrèle avec le stade d’évolution de la maladie. De même, des analyses préliminaires des protéines contenues dans des VE ont permis de révéler que 8 protéines étaient différemment modulées chez les patients, comparativement aux sujets contrôles. Ces résultats préliminaires doivent maintenant être reproduits sur de plus grandes cohortes de patients comprenant 200 patients contrôles et 200 patients atteints de la MP afin de prouver la robustesse de nos biomarqueurs. Les résultats pourraient également mener à l’identification de nouvelles avenues thérapeutiques ciblant plus spécifiquement le système immunitaire. | francesca.cicchetti@crchudequebec.ulaval.ca |
| Data | Dr. Juan Li | Dr. Michael Schlossmacher | Ottawa Hospital Research Institute (OHRI)/ University of Ottawa | Validation of the PREDIGT Score for the Incidence of Parkinson's Disease compared to Healthy Subjects | We previously created and published the PREDIGT Score model as a simple-to-use formula to calculate the incidence of Parkinson disease (PD) based on five known risk categories: Exposome as the sum of environmental exposures (E); genetic susceptibility (DNA variants; D); the presence of tissue changes from documented gene-environment Interactions (I); sex/Gender (G); and age, as in the passage of Time (T). We had further proposed (and modeled) that a final risk score can be calculated by assigning values to each category, as computed by the formula: PR=(E+D+I)xGxT. We also created a 2-step version for population screening purposes. In Step 1, a preliminary risk score was generated based on self-reported answers from validated questionnaires, followed by Step 2, in which the result from one objective clinical assessment (out of seven tested) was used for final classification. The PREDIGT Score has been assessed using two established case-control cohorts: DeNoPa and PPMI. The results demonstrate a promising performance of the original PREDIGT Score in distinguishing newly diagnosed Parkinson’s patients from healthy controls without reliance on a motor examination. To further assess the model’s discriminative performance, especially in Canadian population, we apply access to the C-OPN dataset and CaPRI and QPN cohorts, for both PD patients and healthy controls. Control data from CaPRI and QPN are crucial to our study to assess the score differences between PD patients and controls, and effect sizes of included risk modulators. The study is the secondary use of de-identified data (self-reported questionnaires, interview responses, and demographic information). All data will be stored in an OHRI owned, password protected computer and can only be accessed and analyzed by research staffs (PI: Michael Schlossmacher, MD; co-Investigator and methodologist: Juan Li, PhD). This study is approved by TOH Ethics Board (OHSN-REB): 20180010-01H, renewal of the study protocol has recently been approved by OHSN-REB. | mschlossmacher@toh.ca |
| Data | Dr. Iris Kathol | Dr. Oury Monchi | University of Calgary | PD-MBI-GEN | The proposed study is a secondary data analysis in the Parkinson’s disease population. No study visits will be conducted in this study. Data for the MBI-C which is available in English or in Québecois French, as appropriate, and blood sample collection will be done via the CaPRI and C-OPN protocols. The total and sub-scores for the MBI-C will be correlated to the genetic analyses to work on the following hypotheses: Hypothesis 1: Specific genetic mutations that are associated with neuropsychiatric or cognitive symptoms in PD can be related with the total score and sub-scores of the MBI-C. Hypothesis 2: Exploratory study using molecular inverted probes will reveal novel associations between genotypes and neuropsychiatric functions assessed by the MBI-C. | oury.monchi@umontreal.ca |
| Data | Ibukun Ojo | Dr. Fang Ba and Dr. Myasaki | University of Alberta | Ethnic and Gender Disparities in Access to Deep Brain Stimulation Surgery | The goal of this project is to address the racism and discrimination in access to deep brain stimulation (DBS) in people with Parkinson’s disease (PD). DBS is a safe and well-established treatment. Our preliminary data showed marked disparities in DBS recipients, with 66% being men and 90% being European descent. The current project aims to assess the factors that have led to a skewed DBS population, including physician, systemic barriers and individual racial, gender and socioeconomic biases. We will investigate the systemic barriers that prevent all qualified patients from accessing this important treatment with equity. We will: 1) Analyze the gender, ethnicity, age, education and socioeconomic differences in access to DBS; 2) Identify the physician, systemic and individual racism, gender bias and socioeconomic factors that limit the access for referral to DBS, 3) Proceed with community engagement to improve the discrepancies in access to DBS. | fb@ualberta.ca |
| Data | Dr. James McVittie | Dr. James McVittie | University of Regina | | Project looks at survival analysis methodologies for combining different types of cohort data (incident & prevalent cohorts primarily) and modelling measurement error in reported onset dates. The goals of the research project are to improve survival estimates for diseases in which data from multiple cohort studies may be available and to understand how uncertainty in onset dates for disease with insidious onset processes, such as Parkinson's disease, may be incorporated into the survival analysis modelling procedures. | james.mcvittie@uregina.ca |
| Data and Material | GP2 Team | Dr. Andrew Singleton | NIH | Global Parkinson’s Genetics Program (GP2) | Global Parkinson’s Genetics Program (GP2) is an ambitious program to genotype >150,000 volunteers around the world to further understand the genetic architecture of Parkinson’s disease (PD). GP2 will perform genotyping on C-OPN DNA samples. DNA will be processed and extracted at the MNI (overseen by Dr. Ziv Gan-Or). The DNA samples will be shipped frozen to the NIH where they will be genotyped on the Illumina Infinium Global Diversity Array (GDA) with the NeuroBooster custom content. This will be used for genome-wide association studies (GWAS, e.g. PD case-control GWAS) but also possibly other analyses (e.g. PD progression GWAS). Further analysis may also be done with the genotyping data including potentially whole genome sequencing. However, no other genotyping is planned at the moment. Following data generation and initial quality control, GP2 data will be returned directly to C-OPN and made available to GP2 members in the shared GP2 workspace. Following complete quality control and data processing, data will be positioned in community-facing platforms for data sharing (for example AMP-PD, https://amp-pd.org/). | singleta@mail.nih.gov |
| Data and Material | Dr. Aarnoud van der Spoel | Dr. Aarnoud van der Spoel | Dalhousie University | Measuring a Parkinson’s biomarker in white blood cells | The enzyme glucocerebrosidase (GBA) is a biomarker for Parkinson's disease. Individuals with low GBA activity are overrepresented among Parkinson’s patients. Measuring GBA activity can help diagnose Parkinson's patients, and possibly forecast how fast their disease will progress. In addition, measuring GBA activity can identify which Parkinson’s patients may benefit from new, GBA-enhancing therapies, and can establish the efficacy of such therapies. To measure GBA activity, various methods are being used, but these methods are not consistent or accurate. We have developed a method to measure GBA activity more accurately and have tested this method in cells grown in our laboratory. We now want to evaluate our new method for measuring GBA activity in white blood cells (peripheral blood mononuclear cells, PBMCs) from healthy individuals (to be obtained from STEMCELL Technologies) and from patients with Parkinson's disease (from C-OPN). Our new method may be more accurate in establishing the GBA status of Parkinson’s patients, allowing for better forecasts of disease progression. In addition, our new method may improve the ability to establish the efficacy of GBA-enhancing therapies. | spoela@dal.ca |
| Data and Material | Meron Teferra | Dr. Ziv Gan-Or | McGill University | The genetics of REM sleep behavior disorder, Parkinson’s disease and other synucleinopathies | In this project we will continue the work we have been doing with QPN, by performing targeted sequencing of ~50 genes that are known or suspected to be involved in PD and similar disorders, including GBA1, LRRK2, SNCA, PRKN and others. Just like with QPN, the genetic data will be shared back with C-OPN, and C-OPN can decide to share it further with anyone who applies to get it and approved by C-OPN. We will use the data to perform association studies between variants in these genes and risk for PD and different PD phenotypes such as age at onset, symptoms etc. Together with the samples, we request simple demographic data including age at onset of PD, age at diagnosis of PD, age at enrollment to the study and sex. | ziv.gan-or@mcgill.ca |
| Data and Material | Catherine Dery | Dr. Nicolas Dupré and Dr. Manon Bouchard | CHU de Québec - Université Laval Research Centre | Association between levodopa-carbidopa dose, plasma vitamin B6 deficiency and polyneuropathy in patients with a parkinsonian syndrome: data from the Canadian Open Parkinson Network | Recently, researchers have observed an association between levodopa-carbidopa dose and plasma vitamin B6 levels in Parkinson's disease patients. B6 deficiency could be induced by the catabolism of levodopa, which requires this vitamin as a cofactor. Vitamin B6 deficiency in the blood could potentially lead to polyneuropathy (i.e. simultaneous dysfunction of numerous peripheral nerves). Our team is planning to analyze data of participants from the Canadian Open Parkinson Network to better understand the potential relationship between levodopa-carbidopa, plasma vitamin B6 deficiency and polyneuropathy. Through this project, we hope to direct the attention of the scientific and medical community toward this poorly studied subject. Our results will contribute to improving the treatment of Parkinson's disease patients through a better understanding of clinical manifestations potentially associated with levodopa-carbidopa intake. | nicolas.dupre@chudequebec.ca |
| Data | Aurélie de Rus Jacquet; C-OPN Team | Dr. Francesca Cicchetti | CHUQ | Clinical perception and management of Parkinson's disease during the COVID-19 pandemic: A Canadian experience | The COVID-19 pandemic has necessitated the social isolation of the population and the rapid implementation of remote care for patients with neurodegenerative diseases. The objective of this study was to explore the perceived impact of confinement in patients with Parkinson's disease and document the effects of gender and living environment. We recruited two cohorts from the Canadian provinces of Québec and Alberta, which differed in the dynamics of COVID-19 spreading at the time of the study, and administered a questionnaire on the perceived effects of confinement on daily living and disease management.
Link to publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407944/
| aurelie.jacquet@crchudequebec.ulaval.ca |
| Registry | Dr. Chrystalina Antoniades | Dr. Chrystalina Antoniades | Oxford University | Online population study on time perception in Parkinson's disease and aged population | Parkinson’s disease is known to affect parts of the brain that are thought to be involved in perceiving the passage of time, but the nature and degree of any actual time perception problems that result is not well understood. The aim of this research is to determine whether time perception is altered in Parkinson’s disease (PD) and whether this can be accurately quantified. If so, measures of changes in time perception could potentially be used in future as a test that could help diagnose PD. | Promoted May 2021 |
| Registry | Dr. Pierre-Yves Therriault | Dr. Pierre-Yves Therriault | Université du Québec à Trois-Rivières | L’utilisation de la domotique en ergothérapie : perception d’utilisateurs atteints de la maladie de Parkinson | Le projet concerne la perception d’utilisateurs atteints de la maladie de Parkinson de l’utilisation de la domotique au quotidien. La domotique se définit par l’ensemble des technologies d’un habitat qui apporte un soutien dans la réalisation de tâches et d’activités ou qui favorise un sentiment de sécurité, de confort ou d’autonomie. Nous nous intéressons à savoir quels aspects de ce type de technologie favorise votre soutien à domicile. Nous souhaitons également savoir comment celle-ci vous aide à réaliser vos activités de la vie quotidienne. Nous aimerions en savoir davantage sur les difficultés qui sont perçues lorsque vous utilisez la domotique. | pierre-yves.therriault@uqtr.ca |
| Registry | Dr. Silke Cresswell | Dr. Silke Cresswell | University of British Columbia | Treating anxiety in Parkinson’s disease with a multi-strain probiotic – a randomized, placebo-controlled trial | Parkinson's disease (PD) is a complex condition that carries a high burden of neuropsychiatric comorbidities. About a third of individuals living with Parkinson's disease have one or more anxiety disorders, resulting in lower quality of life, greater care dependency, and increased caregiver burden. Gastrointestinal dysfunction is very common in Parkinson's. Constipation is experienced by the vast majority of patients and often manifests years before onset of motor symptoms, symptoms suggestive of irritable bowel syndrome are also commonly found in PD. Increased intestinal permeability has been demonstrated in PD. Impaired intestinal barrier function can lead to chronic systemic low-grade inflammation, which has been strongly associated with mood disorders. Several lines of evidence suggest a link between the gut microbiome and Parkinson's disease. In summary, given the high rate of anxiety in PD, the growing evidence that probiotics may improve anxiety and mood disorders in non-PD populations, and the strong links between the gut microbiome and PD, we will carry out a randomized, blinded, placebo-controlled study into the use of a multi-strain probiotic to improve anxiety and Parkinson's disease. | silkec@mail.ubc.ca |
| Registry | Dr. Madeleine Sharp | Dr. Madeleine Sharp | McGill Univeristy | Deep cognitive endophenotyping of Parkinson’s disease: A platform development and pilot study. | The purpose of this study is to use computer tests of cognitive function, inspired by the tests used in laboratory animals, to arrive at a better understanding of the mechanisms underlying cognitive symptoms in Parkinson’s disease. | madeleine.sharp@mcgill.ca |
| Registry | Dr. Ryan D'Arcy | Dr. Ryan D'Arcy | University of British Columbia | Multimodal neuromodulation in individuals with Parkinson's Disease | The purpose of the study is to support the development of evidence-based treatments for Parkinson’s disease (PD) by exploring the effect of multimodal non-invasive neurostimulation paired with intensive physical therapy on motor function, cognition, and quality of life in individuals with PD. The results of this preliminary clinical study will inform the development of a larger scale trial investigating this novel multimodal neurostimulation intervention. This neurostimulation study includes translingual neurostimulation delivered using the PoNSTM device and galvanic vestibular stimulation (GVS), combined with a physical therapy program. The study will compare physical therapy alone to physical therapy + neurostimulation. | rdarcy@sfu.ca |
| Registry | Dr. Tejas Sankar | Dr. Tejas Sankar | University of Alberta | Changes in spinal reflexes used post-operatively as a biomarker for optimized treatment from deep brain stimulation in Parkinson's disease | We want to find a potential biomarker helpful for early PD detection, confirming the diagnosis, measuring disease progression, or serving as outcome measures in clinical trials. We will measure the activity of a muscle or group of leg muscles with electrode stickers placed on the skin over the muscle. These surface stickers have many recording contacts to measure the activity from all over the muscle. We want to characterize abnormalities identifiable in the recorded muscle activities by comparing the muscle activities from PD participants with collected data (similar condition) from healthy participants of the same age and sex. We also want to know how the muscle activity changes after clinical PD treatments, including medication and deep brain stimulation (DBS). In addition, our method for muscle activity recording can also tell us how the motor neurons in the spinal cord that activate the muscles are affected by PD. | tsankar@ualberta.ca |
| Registry | Dr. Richard Camicioli and Dr. Kelvin Jones | Dr. Richard Camicioli and Dr. Kelvin Jones | University of Alberta | Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3 | SPARX3 is an NIH-funded, phase 3, multi-site, randomized, evaluator-masked, study of endurance treadmill exercise on changes in the MDS-UPDRS Part III score at 12 months. 370 participants will be randomly assigned to 2 groups: 1)60-65% HRmax or 2)80-85% HRmax 4 times per week. Secondary objectives will test hypotheses related to striatal specific binding ratio (SSBR) at 12 months, MDS-UPDRS Part III score, ambulatory mobility (6-minute walk), daily walking activity (steps), cognition, quality of life, cardiorespiratory fitness, blood-derived biomarkers of inflammation and neurotrophic factors at 12 and 18 months. Exploratory objectives will test hypotheses related to the effects of removing the study support that was provided over 18 months on the sustainability and durability of the exercise effects at 24 months. | rcamicio@ualberta.ca; k.e.jones@ualberta.ca |
| Registry | Dr. Ayse Kuspinar | Dr. Ayse Kuspinar | McMaster University | Development of a new health-related quality of life measure for Parkinson’s disease | Evaluating health-related quality of life is important when measuring the costs and effects of a disease and its treatment. However, a limitation with existing quality of life questionnaires used to measure cost-effectiveness is that they are generic and do not reflect health concerns important to people with Parkinson's Disease (PD). Our research team has developed a new health-related quality of life questionnaire for people with PD, the Preference-Based PD Index (PB-PDI). The PB-PDI, which was developed through quantitative methods and cognitive debriefing with people with PD, includes 7 items with 4 response options each. The aim of this project is to generate preference weights for each item in the PB-PDI and develop a scoring algorithm. The Discrete Choice Experiment methodology, which involves presenting respondents two scenarios and asking them to choose the one they prefer, will be used to determine how important each item is from the perspective of people with PD. This information will help generate preference weights and a scoring algorithm for the PB-PDI. | kuspinaa@mcmaster.ca |
| Registry | Dr. Penny MacDonald | Dr. Penny MacDonald | University of Western | Establishing definitive MRI diagnostic testing of Parkinson's disease | No difinitive diagnostic test of PD currently exists. This imaging biomarker will be tested in PD, atypical PD (such as MSA, PSP, CBS, ET) as well as matched controls. Positive results will enable research to evaluate true disease-modifying therapies more precisely and quickly, and empower physicians to start medications in PD more promptly and manager earlier stages of disease. | penny.macdonald@gmail.com |
| Registry | Dr. Martin McKeown | Dr. Martin McKeown | University of British Columbia | Development of a new health-related quality of life measure for Parkinson’s disease | The long-term goal of this research program is to create privacy-compliant automated assessment of Parkinson’s Disease (PD) based on machine learning algorithms applied to video recordings. Development of such a tool will:
• Facilitate the remote assessment of people with PD
• allow for quantification of disease severity for clinical trials
• empower people with PD to be able to track their own disease.
• Streamline visits in the clinic, allowing for the clinician to focus on other factors that may affect quality of life (e.g. non-motor symptoms);
• allow for non-expert clinicians to automatically assess disease severity
To accomplish this long-term goal, a large-scale, multi-centered, high-quality movement video dataset from patients with PD needs to be established. Crucially, we are developing novel “labelling functions” that allow for automated labelling of most of the videos, with manual labels by clinical experts only reserved for “difficult” cases.
We are using a UBC-sanctioned privacy-compliant means to capture the remote video data (Qualtrics Survey). (Note: while we are using Qualtrics Survey as an online vehicle to remotely capture data, the “survey” here is not a set of questions, but actually a sequence of video instructions and a means to capture video of people performing simple tasks such as finger tapping, providing different facial expressions, etc.) | martin.mckeown@ubc.ca |
| Registry | Dr. Kathryn Lambert | Dr. Ada Leung | University of Alberta | Examining the contribution of executive functions to motor imagery ability in people with Parkinson's disease and healthy older adults | This research project is a part of my doctoral thesis. I will be examining the relationship between executive function in Parkinson’s Disease and the ability to imagine movements. Participants will be asked to meet with the researcher twice in person to complete a battery of tests that assess mood, cognition, motor function, and motor imagery ability. The purpose of the project is two fold. First, understanding the relationship between these two domains may provide further insight into how executive function affects motor planning/control in Parkinson’s Disease, as motor imagery is highly intertwined with the execution of physical movements. Second, motor imagery training is of increasing interest as a rehabilitation tool. The results of this study will indicate whether individuals with executive dysfunction are appropriate for such training (as imagery ability can determine training benefits). | kjlamber@ualberta.ca |
| Data | Lorraine Kalia | Dr Kalia Lorraine | Toronto Western Hospital: University Health Network (UHN) | Cultural Considerations in Daily Levodopa Equivalent Dosage: A Study of Global Population | Levodopa equivalence dosage (LED) is a concept used in the field of Parkinson's disease (PD) to standardize the comparison of different dopamine replacement therapies. Levodopa, the most effective medication for PD, is often combined with other drugs to manage symptoms and improve quality of life. However, the potency of these medications can vary, making it challenging to determine the appropriate dosage.
The concept of LED provides a measure that allows for comparing the efficacy of various medications in terms of their levodopa-like effect. By calculating the LED, healthcare professionals can assess the total daily dose of levodopa that would produce similar clinical benefits as the combination of different drugs.
Currently, LED calculation methods such as the Tomlinson et al. and the Ferreira et al. formulas are widely used. These formulas consider the dosage of levodopa, as well as other medications such as dopamine agonists and monoamine oxidase-B inhibitors. By standardizing the LED, healthcare providers can optimize treatment plans, adjust dosages, and minimize potential side effects. Further recently new proposal by Jost ST (2023), has been published to include all the therapies in use as on date.
While the concept of LED has been extensively studied and implemented in various populations, there is a paucity of data specifically focused on South Asian populations. Understanding the LED requirements in this group is crucial due to potential variations in genetics, lifestyle, and other factors. Further research in this area will enhance personalized treatment strategies and improve the management of Parkinson's disease. | lorraine.kalia@utoronto.ca |
| Data and Material | PhD Nikhil Parag Bhagwat | PhD Nikhil Parag Bhagwat | McGill University | Quebec Parkinson Network cohort: A standardized and preprocessed neuroimaging and clinical dataset for PD biomarker discovery | | nikhil.bhagwat@mcgill.ca |
| Data | Dr Aurélie de Rus Jacquet | Dr Aurélie de Rus Jacquet | Centre de recherche du CHU de Québec-Université Laval | Postal code results for the requested cohort. | | aurelie.jacquet@crchudequebec.ulaval.ca |
| Data and Material | Mathieu Blais | Dr Nicolas Dupré | CHU de Québec – Université Laval | Étude épidémiologique et génétique de la maladie de Parkinson au Québec | The study aims to determine how environmental factors, lifestyle habits, medical factors and genetic variations can lead to the onset of the neurodegenerative disease Parkinson's. Studying these factors could clarify the understanding of this disease and lead to the development of better diagnostic tests and even new treatments. The requested data will be used precisely in the context of the above-mentioned objectives in order to generate new hypotheses. This will be done in collaboration with Prof. Aurélie de Rus Jacquet at Université Laval. | mathieu.blais@crchudequebec.ulaval.ca |
| Data | Gabriel David Pinilla | Dr Oury Monchi | Centre de recherche de l'IUGM
Université de Montréal (Quebec) | | | gabriel.david.pinilla.monsalve@umontreal.ca |
| Data and Material | Cristiane Ribeiro Chaves | | Laboratoire de recherche en audition et vieillissement - CRIUGM | | | cristiane.ribeiro.chaves@umontreal.ca |
| Data | Alavash Mohshen | Prof. Dr. med. Thomas Münte | University of Lübeck | Studying brain resting-state neural dynamics in Parkinson disease using MEG and their relation to clinical outcomes | Studying brain resting-state neural dynamics in Parkinson disease using MEG and their relation to clinical outcomes | mohsen.alavash@uni-luebeck.de |
| Data | Nicolas Ferry | Dr Aurélie de Rus Jacquet | McGill University | | PBMCs and plasma from 10 PD and 10 healthy donors | nicolas.ferry@mcgill.ca |
| Data and Material | Aymeric Lanore | Dr Jean-Christophe Corvol | Paris Brain Institute | ICDs result from an interaction between genetic susceptibility, suggested by previous studies, risk factors such as young age and family history of drug addiction, and environmental circumstances, which in PD would be mainly represented by exposure to DA. We aim to perform a survival GWAS to associate the presence of ICD adjusted for sex and age at diagnosis, the results will be meta-analysed with other cohorts using METAL. The final aim of the study is to clarify the mechanisms involved in the pathophysiology of ICDs.
Clinical characteristics will be used according to their availability in the different cohorts involved in the study, among the following: cohort, sex, age at diagnosis of PD and ICD. ICDs must be assessed by QUIP, QUIP-RS or item 1.6 of the MDS-UPDRS, but other scales will also be taken into account if available).Genotyping of cohorts with genotypic imputation if available. | In Parkinson’s disease (PD), the therapeutic strategy is based on the dopamine replacement therapy. Although available since the 1960s’, it is only relatively recently that behavioral disorders associated with these drugs have been described.
Gathered under the term of “behavioral addiction”, they include impulse control disorders (ICDs), dopamine dysregulation syndrome (DDS), and punding. Interestingly, whereas addiction to L-dopa itself occurs quasi exclusively with L-dopa, ICDs appear electively under dopamine agonist (DA) therapy.
In PD, the prevalence of these disorders ranges from 10 to 17%, far more than in the general population, in which there are estimated at 2-3%. ICDs in PD represent an important Public Health problem because of their familial, social, economic or legal impact.
If very few data are available on the genetic risks for DA associated ICDs, heritability of the trait is known to be higher than 50% in both the general population and PD patients: clinical risk factors do not explain the high variability of the occurrence of ICDs in PD, and genetic factors may explain a substantial part of it.
The main objective of this proposal is to elucidate the genetic basis of DA induced ICDs in PD patients from several international cohorts. The specifics aims are to identify genetic variants, genes or pathways associated with DA induced ICDs and dissect their effects and interaction with drugs, using a genome-wide approach.
We will aggregate phenotypic and genetic data from different pre-existing cohort of PD patients, to test for association between genetic variants, genes or pathways, and the occurrence of ICDs. For clinical data we will use gender, age at onset of PD, age at diagnostic of PD and presence of ICD at visit (ICDs should be evaluated by QUIP, QUIP-RS or item 1.6 of MDS-UPDRS).
For genetic data, Considering 25% of ICD events and genetic risks between 1.6 and 2 for a critical alpha of 5x10-8 and a log-additive model, a sample size respectively between 3200 and 7500 would be needed to reach 70% power to uncover association of variants with 5% minor allele frequency (MAF).
For joint testing of genes and pathways, critical alpha would reduce to approximately 2.5x10-6 and 2.5x10-5, allowing to detect genes using sample sizes between 2400 and 5700 samples and pathways using sample sizes between 1000 and 4700 samples, considering the same characteristics as mentioned for SNVs.
By analyzing the association of both genetic variants and biologic entities with DA induced ICDs, our project will bring important insights on the genetic determinants and mechanisms of ICDs in PD patients.
This may help prevent the occurrence of such disorders not only by predicting the risk of developing ICDs, but also by identifying potential new therapeutic targets. | aymeric.lanore@icm-institute.org |
| Data | Gail Dimapilis | Dr Fang Ba | University of Alberta | Ethnic and Gender Disparities in Access to Deep Brain Stimulation Surgery for Movement Disorders. | We requested for patients who received DBS implants, their demographics and socio-economic data. We also want to exclude the Alberta data, as we have collected data in our center. | gdimapil@ualberta.ca |
| Data | Dr Aurélie de Rus Jacquet | Dr Aurélie de Rus Jacquet | Centre de recherche du CHU de Québec-Université Laval | | Control with psychatric diagnostic | aurelie.jacquet@crchudequebec.ulaval.ca |
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