Investigating idiopathic anosmia as a prodromal state of Parkinson's disease

Abstract Background: Loss of smell commonly predates the diagnosis of Parkinsons disease (PD). However, smell loss has multiple causes, and the relationship between idiopathic anosmia (IA) and PD remains incompletely understood. Objectives: To assess the presence of prodromal features of PD in individuals with IA and to examine the relationship between anosmia duration and prodromal features. Methods: Within the PREDICT-PD study, patients with IA investigated at specialist smell clinics were compared with healthy controls at low risk of PD (HC) and patients with PD. In person assessments included MDS-UPDRS I-III, functional motor tasks, cognitive tasks, autonomic symptoms, orthostatic hypotension, pain, sleep and mood. We compared these features and PD risk according to the PREDICT-PD algorithm between the groups and examined the relationship between the duration of anosmia and severity of prodromal features using linear regression models. Results: We recruited 42 IA, 28 HC and 22 PD participants, matched for age and gender. Overall motor scores were not different between IA and HC. IA had worse cognition, sleep, pain, depressive and some symptoms of dysautonomia than HC, with trends towards worse anxiety scores and higher PD risk scores. Shorter duration of anosmia was negatively correlated with MDS-UPDRS II scores but no other prodromal feature. Conclusions: Some individuals with IA exhibit non-motor features suggestive of prodromal PD. This supports the known association of olfactory dysfunction with subsequent PD but suggests that, even after excluding secondary causes of anosmia, other conditions may underlie anosmia or smell loss may be temporally remote from PD.