Premotor Parkinson's disease: clinical features, detection, and prospects for treatment

The period immediately before the onset of motor symptoms of Parkinson's disease (PD) often has a recognizable phenotype with features including autonomic dysfunction and impaired olfaction. Subclinical dopaminergic cell loss can also be detected at this time using molecular imaging techniques. A greater recognition of the features of premotor PD and improvements in screening technologies have opened the possibility of predictive testing for PD. In addition to molecular imaging of the dopamine system, screening tests that can potentially be used to identify the physiological abnormalities in premotor PD include olfactory testing, imaging of the sympathetic innervation of the heart, transcranial ultrasound, and genetic testing for mutations known to cause hereditary PD. All of these technologies have trade-offs as screening tests for accuracy, availability, and costs. Using these tests in combination may produce a more favorable combination of reasonable cost and accuracy than using any single test alone. Ultimately, the value of screening for PD depends on development of neuroprotective treatments for PD that would create an imperative for early identification and treatment.