Association of Olfactory Loss With Cognition Is Mediated by Striatal Dopamine Loss and Cerebral Perfusion in Parkinson's Disease

PURPOSE: Hyposmia is a common early non-motor symptom of Parkinson disease (PD) and has been linked to cognitive decline. This study investigated whether striatal dopaminergic degeneration and cerebral perfusion deficits mediate the relationship between hyposmia and cognition in PD. PATIENTS AND METHODS: We retrospectively analyzed 343 newly diagnosed PD patients who underwent the Cross-Cultural Smell Identification Test (CCSIT) and dual-phase 18 F-FP-CIT PET. Early-phase PET was used as a surrogate of regional cerebral blood perfusion, and late-phase PET measured dopamine transporter (DAT) availability in 6 striatal subregions. A subset of 219 patients completed baseline neuropsychological testing and were followed for a mean of 4.2 years to assess dementia conversion. RESULTS: Baseline CCSIT scores were positively correlated with DAT availability across striatal regions, strongest in the posterior putamen (β=0.21, P