Olfactory testing combined with dopamine transporter imaging as a method to detect prodromal Parkinson's disease

Objective Olfactory dysfunction is an early and common symptom in Parkinson disease (PD). Previously, the authors demonstrated that idiopathic olfactory dysfunction in first-degree relatives of PD patients is associated with an increased risk of developing PD within 2 years. The aim of the present study was to determine the value of combined olfactory testing and SPECT scanning in predicting future PD in the same population of relatives over a 5-year period. Methods In a cohort of 361 non-parkinsonian, non-demented first-degree relatives of PD patients, a combination of olfactory processing tasks was used to select groups of hyposmic (n=40) and normosmic (n=38) individuals for a 5-year clinical follow-up evaluation and sequential SPECT scanning, using a dopamine transporter ligand to assess nigrostriatal dopaminergic function at baseline and 5 years from baseline. A validated questionnaire, sensitive to the presence of parkinsonism, was used in the follow-up of the remaining 283 relatives. Results Five years from baseline, five out of the 40 hyposmic relatives fulfilled clinical diagnostic criteria for PD. None of the other 349 relatives available for follow-up developed PD. All hyposmic individuals developing PD had an abnormal baseline SPECT scan. Discussion In conclusion, idiopathic hyposmia in first-degree relatives of PD patients is associated with an increased risk of developing clinical PD of 12.5% over a 5-year period. The present data suggest that a two-step approach using olfactory testing followed by SPECT scanning in hyposmic individuals has a very high sensitivity and specificity in detecting PD. The usefulness of this two-step approach needs to be confirmed in larger populations.