Introduction Clinical, neuroimaging and pathological studies suggest that there is a lengthy pre-motor phase of Parkinson disease (PD) during which nigral and extra-nigral neu-rodegeneration precedes the onset of motor symptoms (Gonera, Van't Hof et al. 1997; Abbott, Ross et al. 2003; Ross, Abbott et al. 2006; Haehner, Hummel et al. 2007). The recognition of this pre-motor phase has revolutionized our understanding of the early stages of PD and provides the opportunity to predict who may be at increased risk for developing PD. During the pre-motor period of PD, biomarkers targeted at the non-motor PD symptoms may play an especially critical role. Recent postmortem studies have provided evidence that synuclein pathology in PD begins in the lower brainstem and ascends to the basal ganglia and eventually affecting cortical regions (Braak, Del Tredici et al. 2003)). The anterior olfactory region represents one of the earliest sites for neurodegeneration in PD and available data from clinical studies suggest that olfactory loss starts between 2 and 7 years before the diagnosis of PD (Markopoulou, Larsen et al. 1997; Berendse, Booij et al. 2001; Ponsen, Stofers et al. 2004; Ross, Abbott et al. 2006). Olfactory deficits are well documented in early PD and olfactory loss in asymptomatic relatives of PD patients has been associated with a 20% risk of DAT deficit and a 10% risk of developing clinical PD within 2 years ((Ponsen, Stofers et al. 2004). Identifying markers of disease that are detectable in this pre-motor period, estimated to be 5-10 years in duration, offers the offers the opportunity to identify individuals at-risk for PD and ultimately initiate disease-modifying therapies with a goal to delay or prevent the onset of motor symptoms.
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