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Cortical atrophy on group analysis. A) The AD group showed bilateral parieto-temporal cortex and bilateral frontal cortex atrophy compared to controls (FWE p < 0.05). B) The IPD group had bilateral frontal cortical atrophic changes compared to controls (uncorrected p < 0.001). AD, Alzheimer's disease; IPD, idiopathic Parkinson's disease; RBD, REM sleep behavior disorder; FWE, family-wise error.
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Background:
Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy.
Objective:
We investigated that dementia with RBD might show distinctive cortical atrophic patterns.
Methods:
A total of 31 patients with idiopathic Parkinson's disease (IPD),...
Citations
... We found that the functional connection between the left VLPFC and right inferior temporal was weakened, and the zFC value was significantly positively correlated with the RBDSQ score. To date, the most consistent finding of gray matter in relation to RBD in PD was volume decrease in the temporal lobes (Ford et al., 2013;García-lorenzo et al., 2013;Kim et al., 2015;Lim et al., 2016;Shady et al., 2019), which supports our findings of functional abnormalities in the inferior temporal region. But we did not find loss of temporal lobe volume in the VBM study, which may be due to the quantitative limitation of statistical ability of the subjects. ...
Rapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson’s disease (PD), however, the exact pathophysiological mechanism is not clear. The prefrontal cortex (PFC), especially ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), and inferior frontal gyrus (IFG) which may play roles by regulating cognitive control processes. The purpose of this study was to investigate whether there is abnormal functional connectivity (FC) maps and volume changes in PD with RBD(PD-RBD). We recruited 20 PD-RBD, 20 PD without RBD (PD-nRBD), and 20 normal controls (NC). We utilized resting-state functional Magnetic Resonance Imaging (rs-MRI) to explore FC changes based on regions of interest (VLPFC, DLPFC, and IFG), and used voxel-based morphology technology to analyze whole-brain volumes by 3D-T1 structural MRI. Except the REM sleep behavioral disorders questionnaire (RBDSQ), the PD-RBD showed lower visuospatial/executive and attention scores than the NC group. The RBDSQ scores were significantly positively correlated with zFC of right DLPFC to bilateral posterior cingulate cortex (PCC) (P = 0.0362, R = 0.4708, AlphaSim corrected) and also significantly positively correlated with zFC of left VLPFC to right inferior temporal (P = 0.0157, R = 0.5323, AlphaSim corrected) in PD-RBD group. Furthermore, abnormal correlations with zFC values were also found in some cognitive subdomains in PD-RBD group. The study may suggest that in PD-RBD patients, the presence of RBD may be related to the abnormal FC of VLPFC and DLPFC, meanwhile, the abnormal FC of DLPFC and IFG may be related to the mechanisms of cognitive impairment.
... RBD in early PD seems to be related to presynaptic dopaminergic denervation in the ventral striatum and the anterior caudate nucleus [171]. A decrease in the volume of temporal lobes in PD patients with RBD has been shown in many studies [132,172,173]. Furthermore, there is a neural loss in the pontomesencephalic tegmentum (PMT) in RBD [174]. ...
... [171] A decrease in the volume of temporal lobes. [132,172,173] Loss of neurons in the region of the PMT. [174] Loss of orexin neurons in the hypothalamus. ...
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. There is a wide range of sleep disturbances in patients with PD, such as insomnia and rapid eye movement (REM) sleep behavior disorder (or REM behavior disorder (RBD)). RBD is a sleep disorder in which a patient acts out his/her dreams and includes abnormal behaviors during the REM phase of sleep. On the other hand, melatonin is the principal hormone that is secreted by the pineal gland and significantly modulates the circadian clock and mood state. Furthermore, melatonin has a wide range of regulatory effects and is a safe treatment for sleep disturbances such as RBD in PD. However, the molecular mechanisms of melatonin involved in the treatment or control of RBD are unknown. In this study, we reviewed the pathophysiology of PD and sleep disturbances, including RBD. We also discussed the potential molecular mechanisms of melatonin involved in its therapeutic effect. It was concluded that disruption of crucial neurotransmitter systems that mediate sleep, including norepinephrine, serotonin, dopamine, and GABA, and important neurotransmitter systems that mediate the REM phase, including acetylcholine, serotonin, and norepinephrine, are significantly involved in the induction of sleep disturbances, including RBD in PD. It was also concluded that accumulation of α-synuclein in sleep-related brain regions can disrupt sleep processes and the circadian rhythm. We suggested that new treatment strategies for sleep disturbances in PD may focus on the modulation of α-synuclein aggregation or expression.
... 20 Among PD-diagnosed individuals, sleep disturbances were more frequent among women than men, with evidence for sex differences in terms of difficulty maintaining sleep, excessive dreaming, but not difficulty initiating sleep. 3 Whereas the bulk of evidence linking sleep disturbance to PD has originated from small clinical studies that often measured sleep disturbance and PD simultaneously while emphasizing the role played by RBD, 3,[15][16][17][18][19][21][22][23][24] epidemiologic studies linking other sleep disturbances to PD are scarce. To date, few of these studies have capitalized on large, prospective cohort studies to examine multiple indicators of sleep disturbance as predictors of future PD diagnosis among postmenopausal women. ...
Objective:
To examine the association of sleep disturbance with Parkinson disease (PD) during 10+ years of follow-up among postmenopausal women, 50 to 79 years of age at baseline.
Methods:
Longitudinal data on 130,502 study-eligible women (mean ± standard deviation baseline age = 63.16 ± 7.20 y) from the Women's Health Initiative Clinical Trials and Women's Health Initiative Observational Study were analyzed. The cohort was followed for 15.88 ± 6.50 years, yielding 2,829 (2.17%) PD cases. Sleep disturbance (habitual sleep duration, insomnia symptoms, obstructive sleep apnea risk factors, sleep aids among those with WHI Insomnia Rating Scale scores (WHIIRS) > 9) was measured at baseline and one follow-up time by September 12, 2005. Cox proportional hazards models evaluated relationships controlling for sociodemographic, lifestyle, and health characteristics.
Results:
PD was significantly associated with long sleep duration (≥9 h) versus a benchmark of 7 to 8 hours (hazard ratio [HR] = 1.296, 95% confidence interval [CI]: 1.153-1.456), WHIIRS (>9 vs ≤9) (HR = 1.114, 95% CI:1.023-1.214), and use of sleep aids (yes vs no) (HR = 1.332, 95% CI:1.153-1.539) among those with WHIIRS > 9. Compared with 7 to 8 hours, short (<7 h) sleep duration was unrelated to PD. Finally, the presence of obstructive sleep apnea risk factors was not associated with PD.
Conclusions:
Among postmenopausal women, sleep disturbance was associated with approximately 10% to 30% increased PD risk after ∼16 years follow-up. Prospective cohort studies with objective exposures and adjudicated outcomes that include men and women of diverse backgrounds are required to confirm and extend these findings.
... The questionnaire reflects severity of RBD clinically by calculating mean scores of 10 RBD-related symptoms, which has been validated in many different languages worldwide including Korean version [32]. In addition, previous studies demonstrated that the clinical severity of RBD based on RBDQ was correlated between sigma band (12)(13)(14)(15) desynchronization of scalp EEG in the central brain region in iRBD [32], or to severity of brain atrophy in RBD with neurodegenerative disorder [50]. A more objective index based on video analysis of PSG has been proposed in recent studies [51,52], which could be another way to examine the clinical severity more objectively that can be considered in the following studies. ...
REM sleep behavior disorder (RBD) could be a predictor of Parkinsonism even before development of typical motor symptoms. This study aims to characterize clinical features and corticomuscular and corticocortical coherence (CMC and CCC, respectively) during sleep in RBD patients with or without Parkinsonism. We enrolled a total of 105 subjects, including 20 controls, 54 iRBD, and 31 RBD+P patients, patients who were diagnosed as idiopathic RBD (iRBD) and RBD with Parkinsonism (RBD+P) in our neurology department. We analyzed muscle atonia index (MAI) and CMC between EEG and chin/limb muscle electromyography (EMG) and CCC during different sleep stages. Although differences in the CMC of iRBD group were observed only during REM sleep, MAI differences between groups were noted during both REM and NREM N2 stage sleep. During REM sleep, CMC was higher and MAI was reduced in iRBD patients compared to controls (p = 0.001, p < 0.001, respectively). Interestingly, MAI was more reduced in RBD+P compared to iRBD patients. In comparison, CCC was higher in iRBD patients compared to controls whereas CCC was lower in RBD+P groups compared to control and iRBD groups in various frequency bands during both NREM N2 and REM sleep stages. Among them, increased CMC during REM sleep revealed correlation between clinical severities of RBD symptoms. Our findings indicate that MAI, CMC, and CCC showed distinctive features in iRBD and RBD+P patients compared to controls, suggesting potential usefulness to understand possible links between these diseases.
... In addition, in a prior report by our group, among PD patients with depressive symptoms, RBD + patients showed lower microstructural integrity compared with RBD − patients [61]. Hippocampal gray matter atrophy is also found in PD-RBD patients [62]. Also, 18F-fluorodeoxyglucose positron emission tomography (18F-PET) and SPECT techniques indicate that hippocampus is part of the RBD-related metabolic network in iRBD patients with impending PD [63][64][65][66]. ...
Background
According to epidemiological studies, Parkinson's disease (PD) patients with probable REM sleep behavior disorder (pRBD) are more prone to develop impulse control disorders (ICDs), which is shown to be present in drug-naïve PD patients, and vice versa.
Objectives
To investigate white-matter integrity differences, with and without comorbid pRBD and ICDs.
Methods
149 de-novo PD patients and 30 age- and gender-matched controls from the Parkinson's Progression Markers Initiative were studied. PD subjects were categorized into four groups with and without these comorbidities. We investigated the white matter integrity differences between these groups.
Results
PDs with only ICDs manifested greater fractional anisotropy (FA) and lower mean diffusivity (MD) in ipsilateral cerebellar connections when compared to controls and to Parkinson's with both comorbid disorders. In contrast, significantly lower FA and higher MD in the ipsilateral fornix-stria-terminalis was observed in PDs with only pRBD compared to controls and to PDs without either comorbid disorder. Also, PDs with only pRBD manifested greater FA in contralateral putamen when compared to controls.
Conclusions
Our results suggest the presence of an underlying neural network in PDs with ICDs, particularly involving cerebellar connections, which makes the subjects susceptible to pRBD. Lower white-matter integrity in the fornix of PDs with only pRBD suggests a neuropathological pathway specific to sleep behavior disorder, independent of impulse control disorders. Greater white-matter integrity observed in PDs without comorbid ICDs, regardless of their comorbid pRBD status, might reflect compensatory mechanisms. Targeted therapies for this particular neuropathology may help prevent these comorbidities.
... Regarding subcortical volumes, probable RBD was associated with volume decrease in the left caudate nucleus, pallidum and There are only a few cross-sectional studies of gray matter volume changes associated with RBD symptoms in PD. Previous voxel-based morphometry (VBM) studies have consistently reported smaller volumes in the posterior part of the brain, including temporal and parietal lobe in PD patients with polysomnography (PSG) confirmed RBD 18,22,27 or those with pRBD 17 compared with PD patients without RBD. One recent study of surface-based cortical thickness changes found significant cortical thinning in the inferior and superior temporal cortex in PD patients with RBD compared with those without RBD 22 . ...
REM sleep behavior disorder (RBD) has a poor prognostic implication in both motor and non-motor functions in Parkinson’s disease (PD) patients. However, to the best of our knowledge no study to date investigated the longitudinal cerebral changes underlying RBD symptoms in PD. We performed the longitudinal study to investigate the association between probable RBD and cortical and subcortical changes in early, de novo PD patients. We studied 78 participants from the Parkinson’s Progression Marker Initiative who underwent structural MRI at baseline and after 2 years. The presence of probable RBD (pRBD) was evaluated using the RBD screening questionnaire. We compared the cross-sectional and longitudinal cortical thickness and subcortical volume changes, between PD patients with and without pRBD. At baseline, we found bilateral inferior temporal cortex thinning in the PD-pRBD group compared with the PD-noRBD group. Longitudinally, the PD-pRBD group revealed a significant increase in the rate of thinning in the left insula compared with the PD-noRBD group, and the increased thinning correlated with decreased cognitive performance. In subcortical volume analyses, the presence of pRBD was linked with volume decrease over time in the left caudate nucleus, pallidum and amygdala. The volume changes in the left caudate nucleus revealed correlations with global cognition. These results support the idea that RBD is an important marker of rapid progression in PD motor and non-motor symptoms and suggest that the atrophy in the left insula and caudate nucleus might be the underlying neurobiological mechanisms of the poorer prognosis in PD patients with RBD.
... II When ANOVA showed significant between-group differences we performed a Hochberg's GT2 post-hoc analysis to clarify which groups were significantly different: *significant effect of group; **although HC and PD patients show significant differences, no difference was found between PD RBD+ and PD RBD-. Post-hoc p-values represented: (1) The negative correlation between RBD symptom severity and hippocampal volume in PD patients is in line with preceding VBM studies (Kim et al. 2016;Lim et al. 2016). In contrast, Scherfler et al. showed a higher density of the bilateral hippocampus in iRBD patients, suggesting neuronal reorganization (Scherfler et al. 2011). ...
Parkinson disease (PD) patients with rapid eye movement (REM) sleep behavior disorder (RBD) have worse motor symptoms and non-motor symptoms than patients without RBD. The aim of this study was to examine underlying differences in brain structure from a network perspective. Baseline data were obtained from Parkinson’s Progression Markers Initiative (PPMI) participants. We divided PD patients and healthy controls (HC) into RBD positive and RBD negative using a cutoff score of ≥5 on the RBD screening questionnaire. HC with probable RBD were excluded. We first carried out a region-of-interest analysis of structural MRIs using voxel-based morphometry to study volumetric differences for the putamen, thalamus and hippocampus in a cross-sectional design. Additionally, an exploratory whole-brain analysis was performed. To study group differences from a network perspective, we then performed a ‘seed-based’ analysis of structural covariance, using the bilateral dorsal-caudal putamen, mediodorsal thalamus and anterior hippocampus as seed regions. The volume of the right putamen was smaller in PD patients with RBD. RBD symptom severity correlated negatively with volume of the right putamen, left hippocampus and left thalamus. We did not find any differences in structural covariance between PD patients with and without RBD. Presence of RBD and severity of RBD symptoms in PD are associated with smaller volumes of the putamen, thalamus and hippocampus.
... The majority of studies (n = 24, 80.0%) examining neuronal injury focused on quantitative assessment of volumes or cortical thickness measures, obtained through volumetric MRI (Auning et al., 2015;Berlow et al., 2010;Bruen et al., 2008;Chung, et al., 2016b;Donovan, Wadsworth, et al., 2014b;Elcombe et al., 2015;Enache et al., 2015;Fujishima et al., 2014;Guercio et al., 2015;Hayata et al., 2015;Huey et al., 2017;Kim et al., 2016;Lebedeva et al., 2014;Mah et al., 2015;Moon et al., 2017;Mori et al., 2014;Reijs et al., 2017;Serra et al., 2010;Son et al., 2013;Starkstein et al., 2009;Sturm et al., 2013;Trzepacz et al., 2013;Tunnard et al., 2011). Segmentation strategies varied between studies. ...
... Night-time behaviour disturbances were not associated with Aβ deposition (18F-AV-45 PET in MCI and AD dementia (Bensamoun et al., 2016)), CSF Aβ 42 (in AD dementia, CN/MCI/AD dementia, and SCD/ MCI, respectively (Engelborghs et al., 2006;Kuo et al., 2015;Reijs et al., 2017)), CSF p-tau in AD dementia (Engelborghs et al., 2006) or CSF t-tau (in AD dementia, and SCD/MCI respectively (Engelborghs et al., 2006;Reijs et al., 2017)) across the diagnostic spectrum. Utilizing whole-brain volume approaches, one study reported more atrophy in posterior and inferior (bilateral temporal and occipital cortices) parts of the brain in patients with AD dementia and rapid eye movement sleep behaviour disorder (Kim et al., 2016), contrasting others who reported no association with night-time behaviour disturbances measured with the Neuropsychiatric Inventory (NPI) (Berlow et al., 2010;Bruen et al., 2008;Huey et al., 2017;Serra et al., 2010). Hippocampal volumes were not associated with night-time behaviour disturbances in SCD/MCI (Reijs et al., 2017) and AD (Berlow et al., 2010). ...
Introduction:
Alzheimer's disease (AD) biomarkers such as amyloid, p-tau and neuronal injury markers have been associated with affective symptoms in cognitively impaired individuals, but results are conflicting.
Methods:
CINAHL, Embase, PsycINFO and PubMed were searched for studies evaluating AD biomarkers with affective symptoms in mild cognitive impairment and AD dementia. Studies were classified according to AT(N) research criteria.
Result:
Forty-five abstracts fulfilled eligibility criteria, including in total 8,293 patients (41 cross-sectional studies and 7 longitudinal studies). Depression and night-time behaviour disturbances were not related to AT(N) markers. Apathy was associated with A markers (PET, not CSF). Mixed findings were reported for the association between apathy and T(N) markers; anxiety and AT(N) markers; and between agitation and irritability and A markers. Agitation and irritability were not associated with T(N) markers.
Discussion:
Whereas some AD biomarkers showed to be associated with affective symptoms in AD, most evidence was inconsistent. This is likely due to differences in study design or heterogeneity in affective symptoms. Directions for future research are given.
... Few studies have used voxel-based morphometry (VBM) to investigate RBD-related gray matter abnormalities in PD, with the most consistent finding being volume loss in the temporal lobes but with other findings including change in the cingulate cortex, posterior regions, and thalamus. [7][8][9][10][11] Another study used deformation-based morphometry (DBM), a technique shown to detect volume changes occurring in PD with better accuracy, 12 and found abnormal volume in several cortical (anterior cingulate, olfactory areas) and ...
... To date, only a few VBM studies have investigated gray matter in relation to RBD in PD, with varying results. [7][8][9][10][11] The most consistent finding was volume decrease in the temporal lobes in PD-RBD compared to PD-nRBD patients, 8,10,11 which we also found. Elsewhere, either local volume changes were found in the cingulate and posterior regions 10, 11 and in the thalamus 7 in PD-RBD compared to PD-nRBD patients, or else no between-group differences were obtained. ...
We aimed to investigate cortical and subcortical brain alterations in Parkinson’s disease patients with polysomnography-confirmed REM sleep behavior disorder (RBD). Thirty Parkinson’s disease patients, including 15 patients with RBD, were recruited and compared to 41 healthy controls. Surface-based cortical and subcortical analyses were performed on T1-weighted images to investigate thickness and shape abnormalities between groups, and voxel-based and deformation-based morphometry were performed to investigate local volume. Correlations were performed in patients to investigate the structural correlates of motor activity during REM sleep. Patients with RBD showed cortical thinning in the right perisylvian and inferior temporal cortices and shape contraction in the putamen compared to patients without RBD. Compared to controls, patients with RBD had extensive cortical thinning and volume loss, brainstem volume was reduced, and shape contraction was found in the basal ganglia and hippocampus. In comparison to controls, patients without RBD showed more restricted thinning in the sensorimotor, parietal, and occipital cortices, reduced volume in the brainstem, temporal and more posterior areas, and shape contraction in the pallidum and hippocampus. In Parkinson’s disease, higher tonic and phasic REM sleep motor activity was associated with contraction of the thalamic surface, extensive cortical thinning, and subtle volume reduction in the middle temporal gyrus. In Parkinson’s disease, the presence of RBD is associated with extensive cortical and subcortical abnormalities, suggesting more severe neurodegeneration in patients with RBD. This provides potential neuroanatomical correlates for the more severe clinical phenotype reported in Parkinson’s disease patients with RBD.
... For instance, rapid eye movement sleep behavior disorder (RBD) has been proven to be an early manifestation of-and to predict the pro- gression of-neurodegenerative diseases with synucleinopa- thy. 6 architecture such as increased wake as well as decreased non- rapid eye movement (NREM) and REM sleep. RBD can also occur in AD but is relatively rare. ...
Study objectives:
The aim of this study is to detect the features of sleep disorder via polysomnography (PSG) based on Chinese pedigree of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17).
Methods:
Five members (two symptomatic patients and three patients with a presymptomatic mutation) from the FTDP-17 pedigree were enrolled, in comparison with 9 patients with Parkinson disease (PD) and 11 control patients. Each patient underwent standard PSG and hypnogram analysis.
Results:
Sleep architecture is affected in the presymptomatic stage of FTDP-17, including total sleep time and sleep efficiency. However, rapid eye movement sleep behavior disorder seems to be exempt from FTDP-17. In hypnogram analysis, five individuals with FTDP-17 exhibited decreased sleep efficiency and disruption of the normal cyclic sleep organization.
Conclusions:
In FTDP-17, striatum and brainstem are the pathological lesions, which may be involved in the pathophysiology of the alterations in sleep architecture. The concrete mechanisms need further investigation.
