Hyposmia as a marker of (non-)motor disease severity in Parkinson\u2019s disease

Dareia S Roos,Jos W R Twisk,Pieter G H M Raijmakers,Richard L Doty,Henk W Berendse

doi:10.1007/s00702-019-02074-0

Abstract

The aim of this study was to evaluate the relationship of hyposmia in Parkinson’s disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression.

Highlights

Hyposmia is one of the most common non-motor symptoms in Parkinson’s disease (PD), with a reported prevalence of up to 90% (Doty et al 1988; Haehner et al 2009; Hawkes et al 1997), that may precede the first motor symptoms by several years (Ponsen et al 2004; Ross et al 2008)
Motor function as measured with UPDRS III was significantly associated with olfaction, in the models in which we adjusted for sex and age (Table 2; Fig. 1)
For each of the non-motor symptoms we assessed, test scores were significantly associated with University of Pennsylvania Smell Identification Test (UPSIT) scores

Summary

Introduction

Hyposmia is one of the most common non-motor symptoms in Parkinson’s disease (PD), with a reported prevalence of up to 90% (Doty et al 1988; Haehner et al 2009; Hawkes et al 1997), that may precede the first motor symptoms by several years (Ponsen et al 2004; Ross et al 2008). Some studies showed a correlation between disease duration and olfactory function (Deeb et al 2010; Ramjit et al 2010), most studies have failed to find this correlation (Cavaco et al 2015; Haehner et al 2009; Hawkes et al 1997; Herting et al 2008; Lee et al 2015; Masala et al 2018). While in some studies hyposmia was associated with disease severity as measured with the Unified PD Rating Scale motor subscale (UPDRS III)

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