Parkinson's disease: before the motor symptoms and beyond.

The understanding of the biology of Parkinson's disease (PD) has advanced rapidly over the past 3 decades. In particular, the early pathological changes described by Braak et al. and the awareness of extensive and clinically relevant premotor manifestations are of diagnostic and therapeutic importance. We review those manifestations and their contribution to the clarification of the pathophysiologic processes of PD, and discuss the implications for treatment of the disease.