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

Neurology ◽  
2020 ◽  
Vol 95 (23) ◽  
pp. e3081-e3092 ◽  
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.

Post-Illumination Pupil Response as a Biomarker for Cognition in α-Synucleinopathies

2021 ◽  
pp. 1-6
Author(s):  
Oliver Steiner ◽  
Jan de Zeeuw ◽  
Sophia Stotz ◽  
Frederik Bes ◽  
Dieter Kunz
Keyword(s):  
Executive Functioning ◽  
Dopamine Transporter ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Cognitive State ◽  
Neurocognitive Disorder ◽  
Sleep Behavior ◽  
Cognitive Domains ◽  
The Brain

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.

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

2019 ◽  
Vol 9 (1) ◽  
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.

scholarly journals Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease

2021 ◽  
Author(s):  
Mario Meloni ◽  
Michela Figorilli ◽  
Manolo Carta ◽  
Ludovica Tamburrino ◽  
Antonino Cannas ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rem Sleep ◽  
Rating Scale ◽  
Sleep Onset ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Double Blind ◽  
Sleep Behavior ◽  
Double Blind Placebo

Abstract Purpose Altered serotonergic neurotransmission may contribute to the non-motor features commonly associated with Parkinson’s disease (PD) such as sleep disorders. The 5-hydroxytryptophan (5-HTP) is the intermediate metabolite of l-tryptophan in the production of serotonin and melatonin. The purpose of this study was to compare the effects of 5-HTP to placebo on REM sleep behavior disorder (RBD) status in patients with PD. Methods A single-center, randomized, double-blind placebo-controlled crossover trial was performed in a selected population of 18 patients with PD and RBD. The patients received a placebo and 50 mg of 5-HTP daily in a crossover design over a period of 4 weeks. Results 5-HTP produced an increase in the total percentage of stage REM sleep without a related increase of RBD episodes, as well as a marginal, non-significant reduction in both arousal index and wake after sleep onset. The self-reported RBD frequency and clinical global impression (CGI) were improved during 5-HTP and placebo treatment in comparison to baseline. 5-HTP significantly improved our patients’ motor experiences of daily living as rated by the Unified Parkinson’s Disease Rating Scale (UPDRS) part II. Conclusions This study provides evidence that 5-HTP is safe and effective in improving sleep stability in PD, contributing to ameliorate patients’ global sleep quality. Larger studies with higher doses and longer treatment duration are needed to corroborate these preliminary findings.

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

2019 ◽  
Vol 12 (2) ◽  
pp. 103-112 ◽  
Author(s):  
Jee-Young Lee ◽  
Eun Jin Yoon ◽  
Yu Kyeong Kim ◽  
Chae Won Shin ◽  
Hyunwoo Nam ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Sleep Behavior ◽  
Olfactory Impairment

Characterization of patients with longstanding idiopathic REM sleep behavior disorder

Neurology ◽  
2017 ◽  
Vol 89 (3) ◽  
pp. 242-248 ◽  
Author(s):  
Alex Iranzo ◽  
Ambra Stefani ◽  
Monica Serradell ◽  
Maria Jose Martí ◽  
Francisco Lomeña ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Rating Scale ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Transcranial Sonography ◽  
Sleep Behavior ◽  
Neurodegenerative Process ◽  
Small Subgroup ◽  
Long Term Follow Up

Objective:To evaluate the presence of prodromal markers of Parkinson disease (PD) in patients with longstanding idiopathic REM sleep behavior disorder (IRBD), a small subgroup of individuals with IRBD with long-term follow-up thought not to be at risk of developing PD.Methods:Demographic, clinical, and neuroimaging markers of PD were evaluated in 20 patients with polysomnographic-confirmed longstanding IRBD and in 32 matched controls.Results:Patients were 16 men and 4 women with mean age of 72.9 ± 8.6 years and mean follow-up from IRBD diagnosis of 12.1 ± 2.6 years. Patients more often had objective smell loss (35% vs 3.4%, p = 0.003), constipation (50% vs 15.6%, p = 0.008), and mild parkinsonian signs (45% vs 18.8%, p = 0.042) than controls. Unified Parkinson's Disease Rating Scale motor score was higher in patients than in controls (5.6 ± 3.5 vs 2.0 ± 2.1, p < 0.0001). Dopamine transporter imaging showed decreased striatal uptake in 82.4% of the patients and transcranial sonography found substantia nigra hyperechogenicity in 35.3%. α-Synuclein aggregates were found in 3 of 6 patients who underwent colon or submandibular gland biopsies. All 20 patients showed clinical, neuroimaging, or histologic markers of PD. Probability of prodromal PD (according to recent Movement Disorders Society research criteria) was higher in patients than in controls (<0.0001), and 45% of patients surpassed 80% probability.Conclusions:Prodromal PD markers are common in individuals with longstanding IRBD, suggesting that they are affected by an underlying neurodegenerative process. This observation may be useful for the design of disease-modifying trials to prevent PD onset in IRBD.

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