Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson's disease

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson's disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended ¹⁸Fluorodopa PET scanning protocol to measure ¹⁸Fluorodopa uptake (K_occ) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the "Sniffin' Sticks" test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson's correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and K_occ and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal ¹⁸Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.