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© 2009 American Academy of Neurology Can we image premotor Parkinson disease?From the Institute for Neurodegenerative Disorders, New Haven, Connecticut. Address correspondence and reprint requests to Kenneth Marek, MD, Institute for Neurodegenerative Disorders, New Haven, CT kmarek{at}indd.org
Pathology and imaging studies have shown that patients with Parkinson disease (PD) have a prolonged period of uncertain duration when vulnerable neuronal populations are degenerating, but typical motor symptoms have not yet developed. This provides both an opportunity—it may be best to test new medications and, ultimately, treat PD patients during this early phase of disease—and a challenge—how to find these premotor PD subjects? Imaging biomarkers targeting the premotor period are critical to elucidate both the onset and progression of premotor PD. Widespread data have demonstrated that dopaminergic imaging can detect PD subjects at the motor symptom threshold. Novel strategies combining dopaminergic imaging with known genetic mutations for PD or early clinical signs and PD-associated symptoms, such as olfactory loss and sleep disturbances like REM behavior disorder, have begun to be used to identify individuals at risk for PD before motor symptoms become manifest. Early studies also have used imaging targeting norepinephrine, serotonin, cholinergic, or other neuronal systems to focus on early cardiac, cognitive, and behavioral symptoms. Imaging of nondopaminergic targets such as inflammation or
Disclosure: Dr Marek has been a consultant for Pfizer, Boehringer Ingelheim, Novartis, GE Health, Alseres, Merck Serono, Lilly, Bayer Schering Pharma, Teva, Elan and has an equity interest in Molecular NeuroImaging, LLC. Dr Jennings has been a consultant for Boehringer Ingelheim and Teva, and is an employee of Molecular NeuroImaging. This article has been cited by other articles:
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-synuclein deposition may provide further insight into the etiology of PD. Given the multiple genetic etiologies for PD already identified, the marked variability in the loss of dopaminergic markers measured by imaging at motor symptom onset, and the clear heterogeneity of clinical symptoms at PD onset, it is certain that many imaging biomarkers with a focus ranging from clinical symptoms to PD pathobiology to molecular genetic mechanisms, will be necessary to fully map PD risk. 
