Among patients with synucleinopathies, severities of putamen dopaminergic denervation, assessed by putamen:occipital cortex ratios of 6-18Ffluorodopa-derived radioactivity, were independent of cardiac noradrenergic denervation, assessed by interventricular septal concentrations of 6-18Ffluorodopamine-derived radioactivity. Scores on the University of Pennsylvania Smell Identification Test (UPSIT) were positively correlated with cardiac 6-18Ffluorodopamine-derived radioactivity, whereas they were unrelated to putamen:occipital cortex ratios of 6-18Ffluorodopa-derived radioactivity, signifying independence of anosmia from putamen dopaminergic denervation in synucleinopathies. In PD, anosmia was associated with physiological evidence of low baroreflex-cardiovagal gain, neurochemical evidence of low baroreflex-sympathoneural gain, and neuroimaging evidence of both cardiac and renal noradrenergic denervation, indicating that in PD anosmia is associated with indices of central and peripheral autonomic failure. Therefore, in alpha-synucleinopathies anosmia, baroreflex failure, and peripheral noradrenergic denervation are related to each other, independently of striatal dopaminergic denervation, and might serve as biomarkers of pre-symptomatic PD. Under a new clinical research protocol (09-N-0010, Biomarkers of Risk of Parkinson Disease) we are addressing whether positive biomarkers of central and peripheral catecholaminergic denervation identify pre-symptomatic PD in people with multiple statistical risk factors.
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