Non-invasive Markers of Neurodegeneration in Movement Disorders (R01)

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Other movement disorders that commonly mimic symptoms of PD include the Parkinsonian variant of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and essential tremor (ET). Taken together, these movement disorders affect over 10 million people in the United States alone. Current diagnostic approaches for PD, MSA, PSP, and ET are based on behavioral signs and clinical judgment, and this can often lead to the incorrect diagnosis, especially early in the course of the disease. In fact, it is estimated that 15% of patients in disease modifying drug trials for early PD do not have PD. Objective, valid, noninvasive, and biologically relevant markers of PD, MSA, PSP, and ET are pivotal for early and accurate diagnosis (trait), and for tracking disease progression (state). Our group has recently shown that diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) can be used to identify mechanisms for basal ganglia dysfunction in individuals with Parkinson's disease. Our preliminary data indicate that DTI and fMRI measures from the basal ganglia and cerebellum show excellent promise for differentiating PD, MSA, PSP, and ET, and for tracking longitudinal disease-specific changes in neurodegeneration. We will recruit 150 individuals for the study: 30 patients with PD, 30 patients with MSA, 30 patients with PSP, 30 patients with ET, and 30 control subjects. In Aim 1, we will use DTI and fMRI of the basal ganglia and cerebellum to focus on the development of a sensitive and specific trait marker for each movement disorder. In Aim 2, we will test the same individuals following 2 years using DTI and fMRI of the basal ganglia and cerebellum to develop state markers of neurodegeneration for each movement disorder. With the large and carefully diagnosed patient population at the Center for Movement Disorders and Neurorestoration and the state-of-the-art MRI facility at the McKnight Brain Institute, our group is uniquely positioned to complete the proposed study. The proposed research is innovative because it will utilize structural and functional imaging modalities with a 32-channel head coil performed on a state-of-the-art 3 Tesla MRI unit. The proposed research is significant because it will be the first study to develop non-invasive trait and state markers for four debilitating movement disorders that affect over 10 million people in the United States.

Goals of Project

• Discovery: Establish neural signatures that differentiate MSA, PSP, ET and PD using diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). Using DTI this study will test the hypothesis that changes in the structural integrity in the basal ganglia and cerebellum differentiate PD, MSA, PSP, ET and healthy controls. Motor fMRI will be used to test the hypothesis that functional changes in the basal ganglia and cerebellum will differentiate PD, MSA, PSP, ET and healthy controls. Advanced statistical methods will be used to combine DTI and fMRI measures to achieve maximum sensitivity and specificity.
• Discovery: Demonstrate that changes in structural integrity and/or functional activity over a 2 year time period are specific for each movement disorder.

Enrollment Goals

• 30 Parkinson's diseases participants
• 30 Multisystem Atrophy particpants
• 30 Progressive Supranuclear Palsy participants
• 30 Essential Tremor participants
• 30 Healthy participants (various ages)

Congratulations, to the University of Florida for enrolling 205 participants (100% of target enrollment) in their PD biomarkers program as of June 3, 2016, and completing, through the PDBP Data Management Resource, electronic documentation of 202 baseline visits and 95 twelve month visits!