Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson's disease

Olfactory dysfunction is a frequent and early feature of Parkinson's disease (PD), often preceding the motor symptoms by several years. Assessment of olfactory deficits may be used in the diagnostic assessment of PD. In this study we investigated the relationship between selective deficits in smell identification and nigrostriatal dopaminergic denervation in patients with PD. Twenty-seven PD patients (Hoehn and Yahr stages I-III) and 27 healthy controls matched for gender and age underwent olfactory testing using the 40-odor University of Pennsylvania Smell Identification Test (UPSIT). PD patients underwent ¹¹C-β-CFT dopamine transporter (DAT) positron emission tomography (PET) imaging and clinical motor examination. We found that total UPSIT scores were significantly lower in the PD than in the control subjects (z = 4.7, p < 0.0001). Analysis of the individual smell scores identified 3 odors with an accuracy of >0.75 for the diagnosis of PD. These odors were banana, licorice, and dill pickle. A PD-specific smell identification score (UPSIT-3) was calculated for these 3 odors. Analysis of the patient PET data demonstrated significant correlations between dorsal striatal DAT activity and the UPSIT-3 (R_S = 0.53, p = 0.0027) and total UPSIT (R_S = 0.44, p = 0.023) scores. UPSIT-3 (R_S = 0.43, p = 0.027) but not total UPSIT (R_S = 0.20, ns) correlated with nigral DAT activity. We conclude that patients with PD have selective hyposmia. A simplified UPSIT smell identification test consisting of 3 PD-selective odors had more robust correlation with nigral and dorsal striatial dopaminergic activity compared with the full UPSIT scores in patients with PD. Assessment of selective olfactory deficits may be used as a simplified olfactory screening test in the evaluation of subjects with possible PD.