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Proposal

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with common symptoms including rigidity, tremors, and bradykinesia. While current medication can alleviate symptoms, no treatment exists to stop or slow neuronal cell death and disease progression. There is an unmet need for a biomarker associated with progression that could aide in development of treatments by monitoring disease progression. Since Magnetic Resonance Imaging (MRI) allows for the measure of gray matter (GM) density in the human brain noninvasively, this study was designed to investigate the association between brain atrophy, measured by MRI, and motor dysfunction in PD subjects, as a biomarker.

MRI and voxel-based morphometry methods were used to investigate GM atrophy and the association with motor impairment in 43 PD and 59 control subjects. T1-weighted whole-brain MRI images were acquired in collaborative studies in Germany and at Indiana University on 3T MRI scanners. Group differences in GM density between PD and control subjects were examined voxel by voxel with SPM12 using cluster-corrected two-sample t-tests. Among PD subjects, associations of GM density with motor dysfunction (measured by UPDRS- III) were analyzed by multiple regression.

Compared to controls, PD subjects show significant GM atrophy in the supplementary motor cortex (p < 0.005). This is a critical brain region, linking cognition to action. Among PD subjects, there is a significant association (p < 0.001) of GM atrophy with motor dysfunction (high UPDRS-III) bilaterally in the superior parietal lobules of the motor cortex. These findings agree with the hypothesis that motor dysfunction is associated with GM atrophy in the motor cortex, and that imaging GM density by MRI is a good display of neurodegenerative progression in PD.

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