Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss in the substantia nigra (SN) and dopaminergic deafferentation in the striatal nuclei. Diffusion tensor tractography (DTT) has been used to document cross-sectional changes in the nigrostriatal pathway (NSP) in PD. Our prospective longitudinal study using DTT revealed significant interval NSP degeneration over a two-year period compared to controls, besides cross-sectional changes in the NSP congruent with current literature. Our results suggested that demyelination may be the dominant factor in NSP degeneration in PD. DTT may be a useful objective biomarker of disease progression in the early stages of PD.