Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder

Abstract

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.

Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease

“…44) MDS-UPDRS-III scores (Postuma et al, 2019) and have shown that motor examination signs have a faster progression 1-2 years before phenoconversion (Fereshtehnejad et al, 2019). Moreover, a study stratifying iRBD patients based on the outcome of DAT-SPECT has reported that, in iRBD with or without dopaminergic denervation, MDS-UPDRS-III scores were equal to 10.5 ± 7.5 (indicative of prodromal Parkinson's disease) and 6.0 ± 4.8, respectively, whereas in healthy control subjects the score was equal to 3.2 ± 3.2 (Dusek et al, 2019). Thus, in our iRBD cohort, the relatively high MDS-UPDRS-III score could result from most patients being close to phenoconversion.…”

The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson’s disease

“… 74 Moreover, a study stratifying iRBD patients based on the outcome of DaTScan TM has reported that, iRBD with or without dopaminergic denervation, had MDS-UPDRS-III scores respectively equal to 10.5 ± 7.5 (indicative of prodromal Parkinson’s disease) and 6.0 ± 4.8, whereas healthy control subjects had a score equal to 3.2 ± 3.2. 75 …”

Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

“…Hyposmia is recognised as one of the earliest prodromal signs of Parkinson's disease and is present in many patients with isolated RBD. 27,28 In a multicentre study of more than 600 patients with isolated RBD, hyposmia was present in 67%, 1 and back-extrapolation of disease (to estimate the time at which olfaction crossed normal control values) has identified evidence of hyposmia more than 20 years before phenoconversion. 13 The Sniffin' Sticks test (Burghardt, Wedel, Germany), 29 comprising multi-use felt-tip style pens, and the University of Pennsylvania Smell Identification Test (UPSIT), 30 which uses single-use scratch cards, are the most frequently used instruments to assess olfaction, with similar discrimination accuracy.…”