Decline of olfactory function in Parkinson’s disease: A ten-year longitudinal study

Background: Olfactory dysfunction is a prodromal sign of Parkinson’s disease (PD) present in up to 90% of patients. However, it is unclear whether or not olfactory function worsens over the course of the disease. Objective: In this study we examined whether the rate of decline of olfactory function in PD patients exceeds the expected age-related decline. Methods: Olfactory function was tested in 90 PD patients at baseline (age at baseline 58.3 years, 68.9% males) and an average 10 years later using the 40-item University of Pennsylvania Smell Identification Test (UPSIT). To screen for concomitant cognitive deficits as a potential confounder, the Mini-Mental State Examination (MMSE) was used. Results: At baseline, the mean UPSIT score was 22 points. Over the average 10-year follow-up period olfactory function decreased in 81.1% of PD patients, even in the youngest patients in whom no age-related decline was expected. The mean decrease was six UPSIT points (p < 0.001), which exceeds the expected age-related decline derived from a previous study. When excluding patients with an MMSE score below 24, reflecting cognitive deficits that might interfere with olfactory test performance, UPSIT score still decreased by almost 7 points over the follow-up period. Conclusions: Olfactory function in PD declines more rapidly with increasing disease duration than can be explained by aging or cognitive decline alone. As such, olfactory function appears to be a clinical marker of disease progression in PD that can be measured non-invasively and deserves consideration as part of multimodal phenotyping to monitor disease progression.