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Treatment challenges in Parkinson's disease.

PD continues to be identified clinically2 by its classic motor features: resting tremor, rigidity, and bradykinesia. Such features all represent dopaminergic dysfunction —more specifically, the progressive loss of nigral dopaminergic affer en tation of the striatum. However, nonmotor symptoms3 such as depression, fatigue, sleep disorders, and impaired cognition are increas ingly recognized as important contributors to the overall healthrelated3-5 and economic5-7 burdens imposed on patients and caregivers.8 Meanwhile, among researchers, descriptions of PD now extend to—and even beyond—a long premotor phase with non-nigral clinical features such as anosmia and dys autonomia.9 In that sense, patients presenting with PD motor symptoms are not truly “early” in the disease.9