Olfactory function is longitudinally associated with semantic fluency in Parkinson's disease: a cohort study

Olfactory dysfunction is an early, common, and progressive symptom in Parkinson's disease (PD). Whether the decline in olfactory function is longitudinally associated with a deterioration of (non-)motor symptoms remains debated.

This study aimed to investigate the longitudinal relationship between olfactory function and (non-)motor symptoms, particularly cognitive decline, in PD patients over a ten-year follow-up period.

Ninety patients were assessed at baseline and after approximately ten years. Olfactory function was measured using the 40-item University of Pennsylvania Smell Identification Test (UPSIT®). (non-)Motor symptoms were evaluated using various scales and questionnaires, including the MMSE to assess global cognitive function. Linear regression was used to analyze the change in olfactory function over time in relation to changes in (non-)motor function, and to determine whether baseline olfactory test scores would be associated with (non-)motor function at follow-up. In a subset of 62 patients, in whom comprehensive cognitive testing was performed, we analyzed the longitudinal relationship between olfactory function and performance on specific cognitive tests.

Statistically significant associations were found between a decrease in UPSIT® scores and decline in MMSE, and between baseline UPSIT® scores and MMSE performance at follow-up. In the subgroup with comprehensive cognitive testing, a decrease in UPSIT® scores was associated with worsening semantic fluency. Furthermore, an association was found between baseline UPSIT® score and semantic fluency at follow-up.

Decline in olfactory function in PD is longitudinally associated with worsening global cognitive function, particularly a deterioration in semantic fluency. Baseline olfactory function may be predictive of later cognitive decline, especially in the semantic domain.