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To verify whether white matter microstructural changes are predictors of declining motor impairment in Parkinson's disease (PD).

A total of 123 patients with early PD were enrolled along with 49 controls. Participants underwent clinical, motor (Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III) and 3T MRI DTI investigations at baseline and 18 month evaluation. Baseline and longitudinal fractional anisotropy (FA) and mean diffusivity (MD) changes were analysed voxelwise using Tract Based Spatial Statistics in generalised linear models. Imaging parameters were analysed using Tract Based Spatial Statistics. The relationships between fractional anisotropy (FA) and mean diffusivity (MD) with motor function were investigated using multiple linear regression. All analyses were controlled for age, sex, disease duration, levodopa dose and visit intervals.

At baseline, patients with PD had significantly higher widespread MD than controls. At follow-up, both groups showed a further significant FA decrease and MD increase. Baseline MD was a significant predictor of worsening of motor impairment in PD (Β (95%CI) 61.07 (15.75; 106.40), p 0.009), whereas FA was not a significant predictor (Β (95%CI) -76.55 (-158.42; 5.32), p 0.067).

MD represents an important correlate and predictor of motor impairment in PD: DTI is potentially a useful tool in stratification of patients into clinical trials and to monitor the impact of treatment on motor function.

This prospective longitudinal large cohort, demonstrated that mean diffusivity is a predictor of future worsening of motor function in early Parkinson's disease. Diffusion tensor imaging is potentially a useful tool in stratification of patients into clinical trials to monitor the impact of treatment on motor function.