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 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

scholarly journals Cortical and subcortical gray matter bases of cognitive deficits in REM sleep behavior disorder

Neurology ◽  
2018 ◽  
Vol 90 (20) ◽  
pp. e1759-e1770 ◽  
Author(s):  
Shady Rahayel ◽  
Ronald B. Postuma ◽  
Jacques Montplaisir ◽  
Daphné Génier Marchand ◽  
Frédérique Escudier ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Gray Matter ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Color Discrimination ◽  
Cognitive Status ◽  
Sleep Behavior ◽  
Cognitive Domains ◽  
Cortical Thinning

ObjectiveTo investigate cortical and subcortical gray matter abnormalities underlying cognitive impairment in patients with REM sleep behavior disorder (RBD) with or without mild cognitive impairment (MCI).MethodsFifty-two patients with RBD, including 17 patients with MCI, were recruited and compared to 41 controls. All participants underwent extensive clinical assessments, neuropsychological examination, and 3-tesla MRI acquisition of T1 anatomical images. Vertex-based cortical analyses of volume, thickness, and surface area were performed to investigate cortical abnormalities between groups, whereas vertex-based shape analysis was performed to investigate subcortical structure surfaces. Correlations were performed to investigate associations between cortical and subcortical metrics, cognitive domains, and other markers of neurodegeneration (color discrimination, olfaction, and autonomic measures).ResultsPatients with MCI had cortical thinning in the frontal, cingulate, temporal, and occipital cortices, and abnormal surface contraction in the lenticular nucleus and thalamus. Patients without MCI had cortical thinning restricted to the frontal cortex. Lower patient performance in cognitive domains was associated with cortical and subcortical abnormalities. Moreover, impaired performance on olfaction, color discrimination, and autonomic measures was associated with thinning in the occipital lobe.ConclusionsCortical and subcortical gray matter abnormalities are associated with cognitive status in patients with RBD, with more extensive patterns in patients with MCI. Our results highlight the importance of distinguishing between subgroups of patients with RBD according to cognitive status in order to better understand the neurodegenerative process in this population.

Acting out Dreams: REM Sleep Behavior Disorder

2013 ◽  
Author(s):  
J. Eric Ahlskog
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Rem Sleep ◽  
Sleep Stage ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Alpha Synuclein ◽  
Sleep Behavior ◽  
The Brain

Normal dreaming occurs during the deepest sleep states. Obviously, if experiencing a frightening dream, sleeping people could be injured if they jumped out of bed and started to run. Fortunately, the brain has a natural protective mechanism during dreaming: body paralysis. During the primary sleep stage in which dreaming occurs, the body’s muscle tone is shut off and muscles become limp. Only the eye muscles are spared, still able to move during a dream. This state in which dreaming takes place is rapid eye movement (REM) sleep. Restated, during REM sleep, a switch is thrown in the brain stem that shuts off body movement during dreaming. People with Lewy disorders of all types often lose this switch function. In other words, they can still move during the dreams of REM sleep. In the midst of a dream, they may act out by yelling, kicking, or hitting the air. This behavior is termed dream enactment behavior. When it is a recurring event it is termed REM sleep behavior disorder. REM sleep behavior disorder occurs in people with Lewy disorders—Parkinson’s disease, DLB, or PDD. It also occurs in another disorder in which alpha-synuclein is abnormally deposited in the nervous system, multiple system atrophy (MSA). Recall from Chapter 2 that alpha-synuclein is present in Lewy bodies and is thought to be a causative factor in all of these conditions. REM sleep behavior disorder may be present years or even decades before the occurrence of DLB, PDD, Parkinson’s disease, or multiple system atrophy. It is often one of the first signs of these disorders, predating most other manifestations. That does not mean that everyone who acts out their dreams will eventually develop Parkinson’s disease, DLB, or MSA. However, it does confer an increased risk. It should be noted that certain medications may provoke REM sleep behavior disorder, such as the commonly used antidepressants. Also, sleepwalking in children should not be confused with this disorder. Sleepwalking occurs in a different sleep stage and is not thought to be a forerunner of Lewy body conditions.

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.

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