Investigators/Authors: Martin McKeown,MD., Silke Appel-Cresswell,MD, University of British Columbia
Objectives: Investigate whether changes in the shape rather than the overall volume of basal ganglia structures represent an early and sensitive marker for the development of motor and non-motor symptoms in PD.
Investigate if iron deposition in the Substantia Nigra pars compacta (SNpc) assessed with the novel MRI method of susceptibility-weighted imaging (SWI) corresponds with disease severity and falls risk.
Background: Functional neuroimaging, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) have been suggested as biomarkers in PD. While they have proved valuable in examining some aspects of the rate of progression of the disease, their use as sensitive biomarkers has not been definitively established. Microglial activation assessed with 11C-(R)-PK95111 is a potential candidate as a biomarker, but two published studies show discrepancies between activation seen in the midbrain and striatum. Impaired cardiac uptake of 123I-MIBG, suggesting sympathetic involvement in PD, has been suggested as an early biomarker in PD. Metabolomic profiling, where many (>1,000) metabolites are probed for characteristics of disease are promising, but it is difficult to separate the core features of the disease with other changes in metabolites due to inter-subject variation and the effects of treatment. Thus unfortunately, for a variety of reasons, ranging from poor sensitivity and specificity, to difficulty in widely disseminating the technology, all biomarkers proposed thus far have not yet developed into clinically useful tools for a broad range of patients. Accurate and widely available biomarkers for early disease remain an elusive goal. While investigators pilot data give them reason to believe that the proposed methods have the potential to predict, in prospective fashion, upcoming deficits, and that these measurements are more sensitive than currently employed techniques such as diffusion tensor imaging and cortical thickness measurements, the purpose of this proposal is the initial validation of these MRI biomarker(s), a necessary first step of the “cascade of processes, each adding confidence to the initial candidate biomarker” necessary for full biomarker validation.
Methods/Design: Investigators will recruit 70 mild-moderate PD subjects, and 30 age and gender-matched healthy controls. Subjects will undergo: clinical assessment consisting of motor evaluation (UPDRS), a battery of neuropsychiatric scales, diagnostic interview and cognitive assessment, as well as balance assessment with a trained physiotherapist, and MRI scanning with a 3T scanner. Using a specialized multidisciplinary team, investigators will compare the MRI results with UPDRS motor scores and clinical measures.
Relevance to Diagnosis/Treatment of Parkinson’s disease: This study will lay the groundwork for further studies that could longitudinally assess the predictive value of the proposed MRI measurements for the development of clinical deficits.
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Investigators/Authors: Anat Mirelman, PhD, Nir Giladi, MD, Tel-Aviv Medical Center, Israel
Objectives: To identify risk factors as well as biological markers of early disease and revel information on the mode of conversion from asymptomatic to PD.
Background: About one third of the Ashkenazi Jewish patients with Parkinson's disease (PD) carry disease associated mutations in the LRRK2 gene. Recent studies from North African countries like Tunisia, Algeria and Morocco have reported that this mutation has been found also in the Arab population in a very high percentage. The age of the founder mutation (G2019S) in the LRRK2 gene among the Arabs of North Africa has been dated to about 5000 years ago while the age of the same mutation among the Ashkenazi Jews population is about 1300 years. The frequency of the G2019S mutation in the LRRK2 gene among Non-Ashkenazi Jews is unknown and neither are the clinical PD features of mutation carriers among those Sephardic Jews. Healthy, first degree relatives of patients with PD are at higher risk to develop PD. The exact risk is unknown but within the Ashkenazi population this risk ranges between 2-20 times higher than those healthy subjects with no family history of PD. With the current understanding that the pathological process in PD, within the brain and peripheral autonomic nervous system, begins 10-20 years prior to the appearance of motor symptoms, and with the increased interest in the development of sensitive biological markers for pre-motor diseased state in PD, there is a special interest in first degree relatives of PD patients as a population at risk which might develop the disease during their lives.
Methods/Design: One hundred PD patients who originated from countries around the Mediterranean Sea will be screened for the G2019S mutation in the LRRK2 gene. Patients with PD will be asked for permission to contact their families by mail. 100 healthy 1st degree relatives of those Sephardic PD patients and 50 healthy subjects with no history of PD in the family, who are over the age 35, will be invited to participate in a 5 years prospective clinical and genetic follow up study. Subjects interested in participation in the study will be invited to the MDU at TASMC for a yearly assessment
Relevance to Diagnosis/Treatment of Parkinson’s disease: Information on risk factors and biological markers of early disease might lead to better clinical counseling to subjects at risk about potential disease modifying measures as well as to the future development of protective therapeutic strategies in order to delay the appearance of motor symptoms
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Investigators/Authors: Chairmen, John Nutt, MD; Medical Director, NPF Center of Excellence at Oregon Health and Science University in Portland, OR, Mark Guttman, MD; Medical Director, NPF Center of Excellence at The Center for Movement Disorders in Markham, Ontario, Tanya Simuni, MD; Medical Director, NPF Center of Excellence at Northwestern University in Chicago, IL, NPF Quality Improvement Initiative Steering Committee
Objectives: Identify correlations between therapeutic choices and improved outcomes; Establish an evidence base as a foundation for future innovation; Improve the body of research to support evidence-based medicine decisions
Background: With an eye toward dramatically changing the quality of care in Parkinson’s disease, NPF launched the Quality Improvement Initiative (“NPF-QII”) in 2009. Committed to an evidence-based approach to quality improvement in care, NPF initiated this project to capture clinical interventions and patient-reported outcomes over time and from multiple centers across the U.S, Canada and internationally. Led by a steering committee of renowned movement disorders neurologists, NPF-QII is unique in its scope, in its capacity to leverage wide clinician participation and in its longitudinal data collection strategy. NPF-QII promises to accelerate clinical discovery, promote collaborative science and drive advancements in clinical practice toward true patient-centered care. Now in its third year, NPF-QII includes over 5,000 patients from 20 centers, with second-year data on 3,000 patients and third year data on almost 500. Over 12 abstracts have been presented at international scientific conferences and more than four papers have been published in specialized peer review journals. The scope and scale of this project is unprecedented in Parkinson’s disease, where no study of patients with a confirmed diagnosis of Parkinson’s disease has ever before been larger than 2,000 patients and no multi-year clinical study has included more than 1,000.
Methods: NPF-QII collects demographic data, information about the patient's Parkinson's disease and other comorbid illness, patient assessments of Parkinson's related physical, emotional and cognitive disability and clinician tests of mobility, memory and cognition. It also collects data on the burden of the disease on caregivers. Any person who receives medical care for the diagnosis of idiopathic Parkinson's disease at any of the participating Centers is eligible to participate in the Registry. There are no limitations for participation based on age, disease severity or presence of cognitive impairments. Registry data will be used to study the relationship between treatment and clinical symptoms of patients with Parkinson's.
Relevance to the diagnosis/treatment of PD: NPF’s Quality Improvement Initiative is building a body of evidence-based knowledge which will be used to drive improvements in the quality and consistency of care for all individuals diagnosed with Parkinson’s disease. In addition, data captured as part of this initiative will support comparative effectiveness research to identify the most effective and cost-effective ways to treat PD patients; identify positive health outcomes associated with various treatment approaches; encourage exploratory data analyses for the development of novel hypotheses for prospective clinical research; enable clinicians to track performance, and ultimately establish targeted metrics for excellent care, and most important, provide an unmatched framework to evaluate new treatments in real-world clinical settings.
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