How Cerebral Plasticity Shapes Symptom Progression in Parkinson's Disease: a Longitudinal Neuroimaging Study
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Parkinson Disease
- Sponsor
- Radboud University Medical Center
- Enrollment
- 115
- Locations
- 1
- Primary Endpoint
- Mid-term disease progression in terms of overall motor symptoms
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Motor symptom progression in early-stage Parkinson's disease varies substantially between individual patients. This progression correlates poorly with striatal dopamine depletion, which is largely complete four years post-diagnosis. Identification of alternative mechanisms, such as cortical compensatory processes, may enable more accurate predictions of individual motor progression.
Detailed Description
Striatal dopamine depletion leads to dysfunction in the cortico-striatal motor circuit and is an important contributor to motor symptoms in Parkinson's disease (PD). However, dopamine depletion in striatal motor regions is already severe at symptom onset and tends to correlate poorly with progressive worsening. This indicates that the severity of motor symptoms in PD may not be solely dependent on basal ganglia dysfunction. In PD, the deleterious effect of basal ganglia dysfunction on motor control may be partially counteracted by neuroplasticity and the compensatory recruitment of parieto-premotor areas of cortex that drive movement based on sensory cueing and goal-directed cognitive control. The efficacy of cortical compensation could therefore be a core determinant of motor impairment in PD. This study utilizes longitudinal clinical and brain imaging data from early-stage PD patients included in the Personalized Parkinson Project (ClinicalTrials.gov Identifier: NCT03364894) to test whether motor symptom severity and progression can be predicted by action selection-related brain activity in parieto-premotor cortex, basal ganglia, or a combination of both. Additional control analyses will be performed to investigate the effects of disease and medication on action selection-related brain activity. Action selection-related brain activity will be compared between PD patients and a cohort of healthy controls to assess the effect of disease (PD vs Healthy). Effects of medication (on vs. off) on action selection-related brain activity will be investigated through within-subject comparisons in subset of PD patients who underwent functional brain imaging in both on- and off-medicated states.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Mid-term disease progression in terms of overall motor symptoms
Time Frame: Baseline and 2 years
Change in Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, measured in off state. This scale assesses 18 motor symptoms (33 items) that are specific for Parkinson's disease. Item scores range from 0 to 4 and are summed, resulting in a total score ranging from 0 to 132, with higher scores representing worse outcomes.
Mid-term disease progression in terms of bradykinesia and rigidity
Time Frame: Baseline and 2 years
Change in Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, measured in off state. This scale assesses 18 motor symptoms (33 items) that are specific for Parkinson's disease. Item scores range from 0 to 4. 17 items assessing bradykinesia and rigidity and are summed, resulting in a total score ranging from 0 to 68, with higher scores representing worse outcomes.