Nonmotor and Dopamine Transporter Change in REM Sleep Behavior Disorder by Olfactory Impairment

Neurodegenerative processes in the brain are reflected by structural retinal changes. As a possible biomarker of cognitive state in prodromal α-synucleinopathies, we compared melanopsin-mediated post-illumination pupil responses (PIPR) with cognition (CERAD-plus) in 69 patients with isolated REM-sleep behavior disorder. PIPR was significantly correlated with cognitive domains, especially executive functioning (r = 0.417, p < 0.001), which was more pronounced in patients with lower dopamine-transporter density, suggesting advanced neurodegenerative state (n = 26; r = 0.575, p = 0.002). Patients with mild neurocognitive disorder (n = 10) had significantly reduced PIPR (smaller melanopsin-mediated response) compared to those without (p = 0.001). Thus, PIPR may be a functional—possibly monitoring—marker for impaired cognitive state in (prodromal) α-synucleinopathies.

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

Scientific Reports ◽

10.1038/s41598-019-51710-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Petr Dušek ◽

Veronika Lorenzo y Losada Ibarburu ◽

Ondrej Bezdicek ◽

Irene Dall’antonia ◽

Simona Dostálová ◽

...

Keyword(s):

Dopamine Transporter ◽

Rem Sleep ◽

Muscle Activity ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Motor Symptoms ◽

Sleep Behavior ◽

Binding Ratio ◽

Dat Spect ◽

Non Motor Symptoms

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.

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Twenty Years After: Another Case Report of Melatonin Effects on REM Sleep Behavior Disorder, Using Serial Dopamine Transporter Imaging

Neuropsychobiology ◽

10.1159/000488893 ◽

2017 ◽

Vol 76 (2) ◽

pp. 100-104 ◽

Cited By ~ 9

Author(s):

Dieter Kunz ◽

Frederik Bes

Keyword(s):

Case Report ◽

Dopamine Transporter ◽

Rem Sleep ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Sleep Behavior ◽

Dopamine Transporter Imaging

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Dopamine transporter imaging predicts clinically‐defined α ‐synucleinopathy in REM sleep behavior disorder

Annals of Clinical and Translational Neurology ◽

10.1002/acn3.51269 ◽

2020 ◽

Author(s):

Lana M. Chahine ◽

Michael C. Brumm ◽

Chelsea Caspell‐Garcia ◽

Wolfgang Oertel ◽

Brit Mollenhauer ◽

...

Keyword(s):

Dopamine Transporter ◽

Rem Sleep ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Sleep Behavior ◽

Dopamine Transporter Imaging

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Longitudinal change in dopamine transporter availability in idiopathic REM sleep behavior disorder

Neurology ◽

10.1212/wnl.0000000000010942 ◽

2020 ◽

Vol 95 (23) ◽

pp. e3081-e3092 ◽

Cited By ~ 2

Author(s):

Jung Hwan Shin ◽

Jee-Young Lee ◽

Yu-Kyeong Kim ◽

Sung-A Shin ◽

Heejung Kim ◽

...

Keyword(s):

Confidence Interval ◽

Dopamine Transporter ◽

Rem Sleep ◽

Rating Scale ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Hazard Ratio ◽

Longitudinal Change ◽

Study Cohort ◽

Sleep Behavior

ObjectiveTo elucidate longitudinal changes in the dopamine transporter (DAT) availability in association with the prodromal markers in idiopathic REM sleep behavior disorder (iRBD), we analyzed a longitudinal prospective iRBD cohort data.MethodThe study cohort consisted of patients with iRBD, individuals with Parkinson disease (PD), and healthy controls. All participants were evaluated for olfaction, neuropsychological tests, and the Movement Disorders Society–Unified Parkinson's Disease Rating Scale and underwent 18F-FP-CIT PET scans every 2 years. We calculated the DAT pattern by performing the principal component analysis of tracer uptakes in 6 striatal regions.ResultDAT patterns in patients with iRBD with baseline hyposmia, constipation, and mild parkinsonian signs distributed toward the PD pattern and clearly distinguished from the healthy control pattern. The DAT pattern moved toward the PD pattern over time in some patients with iRBD during the follow-up, and baseline hyposmia was the only biomarker significantly associated with this change. Baseline PD pattern of DAT predicted 58% of disease converters (hazard ratio 4.95 [95% confidence interval 1.16–21.08]). The combination of hyposmia and baseline PD pattern of DAT predicted 67% of the conversion (hazard ratio 7.89 [confidence interval 1.85–33.69]). The estimated sample size required for a simulated neuroprotective clinical trial was 63 per group when the annual change of DAT pattern was used as an outcome in the subgroup with baseline DAT PD pattern and hyposmia, which is the smallest number reported so far.ConclusionBaseline and longitudinal monitoring of the DAT pattern can be a useful biomarker in identifying individuals with a high risk of disease conversion and in selecting the potential population for clinical trials in iRBD.

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