Probable Rapid Eye Movement Sleep Research Articles

Cortical Macro- and Microstructural Changes in Parkinson's Disease with Probable Rapid Eye Movement Sleep Behavior Disorder.

Evidence regarding cortical atrophy patterns in Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-pRBD) remains scarce. Cortical mean diffusivity (cMD), as a novel imaging biomarker highly sensitive to detecting cortical microstructural changes in different neurodegenerative diseases, has not been investigated in PD-pRBD yet. The aim was to investigate cMD as a sensitive measure to identify subtle cortical microstructural changes in PD-pRBD and its relationship with cortical thickness (CTh). Twenty-two PD-pRBD, 31 PD without probable RBD (PD-nonpRBD), and 28 healthy controls (HC) were assessed using 3D T1-weighted and diffusion-weighted magnetic resonance imaging on a 3-T scanner and neuropsychological testing. Measures of cortical brain changes were obtained through cMD and CTh. Two-class group comparisons of a general linear model were performed (P < 0.05). Cohen's d effect size for both approaches was computed. PD-pRBD patients showed higher cMD than PD-nonpRBD patients in the left superior temporal, superior frontal, and precentral gyri, precuneus cortex, as well as in the right middle frontal and postcentral gyri and paracentral lobule (d > 0.8), whereas CTh did not detect significant differences. PD-pRBD patients also showed increased bilateral posterior cMD in comparison with HCs (d > 0.8). These results partially overlapped with CTh results (0.5 < d < 0.8). PD-nonpRBD patients showed no differences in cMD when compared with HCs but showed cortical thinning in the left fusiform gyrus and lateral occipital cortex bilaterally (d > 0.5). cMD may be more sensitive than CTh displaying significant cortico-structural differences between PD subgroups, indicating this imaging biomarker's utility in studying early cortical changes in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Minor hallucinations in Parkinson's disease with probable rapid eye movement sleep behavior disorder.

Rapid eye movement sleep behavior disorder (RBD) and minor hallucinations (MHs) are prevalent nonmotor symptoms in Parkinson's disease (PD). The purpose of this study was to explore the association of MHs in PD patients with probable RBD (pRBD). This cross-sectional study included 291 patients diagnosed with PD. Patients who scored 6 or higher on the Rapid Eye Movement Behavior Disorder (RBD) Screening Questionnaire were defined as pRBD. A comprehensive evaluation was performed for all patients, including the collection of demographic information, clinical assessment, and MH features. Among the 291 PD patients, 69 (23.7%) had pRBD. MHs were observed in 35 (50.7%) patients with pRBD, significantly higher than 29.7% in patients without RBD (p = 0.015). The main type of MHs in pRBD was presence hallucinations with variable content. Patients with pRBD and MHs tended to be older, had a longer disease duration, and were more likely to take levodopa or dopamine-receptor agonists. Besides, the pRBD with MHs group had higher scores on the Nonmotor Symptoms Questionnaire (NMS-Quest) and Hamilton Anxiety Scale (HAMA). Binary logistic regression analysis revealed that longer disease duration and higher NMS-Quest scores were associated with MHs in PD patients with pRBD. A high prevalence of MHs was observed in PD patients with pRBD. The main type of MHs in pRBD was presence hallucinations. MHs in PD with RBD are mainly associated with disease duration and severity of nonmotor symptoms. These findings provide new insights into the interaction between MHs and RBD.

Comparison of different risk scores for Parkinson disease in a population-based 10-year study.

Different algorithms aiming to identify individuals at risk of Parkinson disease (PD) have been proposed. Comparative studies of these scores and their recent updates in the general elder population are needed. We have previously applied the "basic" PREDICT-PD algorithm, designed for remote screening, and the original and updated Movement Disorder Society (MDS) criteria for prodromal PD to the longitudinal population-based Bruneck study cohort. We have now additionally employed the "enhanced" PREDICT-PD algorithm (which includes motor assessment, olfaction, probable rapid eye movement sleep behaviour disorder status, pesticide exposure, and diabetes as additional factors). Risk scores were calculated based on comprehensive baseline assessments (2005) in 574 subjects aged 55-94 years (290 females), and cases of incident PD were identified at 5-year (n = 11) and 10-year follow-up (n = 9). We analysed the association of the different log-transformed risk scores with incident PD at follow-up (calculated per 1-SD unit change). The enhanced PREDICT-PD algorithm was associated with incident PD over 10-years of follow-up, yielding higher odds for incident PD (odds ratio [OR] = 4.61, 95% confidence interval [CI] = 2.68-7.93, p < 0.001) compared with the basic PREDICT-PD score (OR = 2.38, 95% CI = 1.49-3.79, p < 0.001). The updated MDS prodromal criteria yielded a numerically higher OR of 7.13 (95% CI = 3.49-14.54, p < 0.001) in comparison with the original criteria as well as the enhanced PREDICT-PD algorithm, with overlapping 95% CIs. The enhanced PREDICT-PD algorithm was significantly associated with incident PD. The consistent performance of both the enhanced PREDICT-PD algorithm and the updated MDS prodromal criteria compared to their original versions supports their use in PD risk screening.

Subjective Cognitive Decline in Women with Features Suggestive of Prodromal Parkinson's Disease.

Cognitive deficits can be present in the prodromal phase of Parkinson's disease (PD). Subjective cognitive decline (SCD) may contribute to identifying individuals with prodromal PD. The objective of this study was to examine whether SCD is more likely to be present in women with features suggestive of prodromal PD compared with women without these features. The study population comprised 12,427 women from the Nurses' Health Study selected to investigate prodromal PD. Prodromal and risk markers of PD were assessed via self-administered questionnaires. We evaluated the association of hyposmia, constipation, and probable rapid eye movement sleep behavior disorder, three major features of prodromal PD, with SCD, adjusting for age, education, body mass index, physical activity, smoking, alcohol, caffeine intake, and depression. We also explored whether SCD was associated with the probability of prodromal PD and conducted additional analyses using data from neurocognitive tests. Women experiencing the three examined nonmotor features had the worst mean SCD score and the highest odds of poor subjective cognition (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.29-2.47). This association persisted when women with objective cognitive deficits were excluded from analyses. SCD was also more common in women with a probability of prodromal PD ≥0.80, particularly among those aged younger than 75 years (OR of poor subjective cognition = 6.57 [95% CI, 2.43-17.77]). These observations were consistent with the results from analyses using neurocognitive tests, where a worse global cognitive performance was observed among women with three features. Our study suggests that self-perceived cognitive decline can be present during the prodromal phase of PD. © 2023 International Parkinson and Movement Disorder Society.

Fall Risk, Sleep Behavior, and Sleep-Related Movement Disorders in Young Urbanites Exposed to Air Pollution.

Quadruple aberrant hyperphosphorylated tau, amyloid-β, α-synuclein, and TDP-43 pathology had been documented in 202/203 forensic autopsies in Metropolitan Mexico City ≤40-year-olds with high exposures to ultrafine particulate matter and engineered nanoparticles. Cognition deficits, gait, equilibrium abnormalities, and MRI frontal, temporal, caudate, and cerebellar atrophy are documented in young adults. This study aimed to identify an association between falls, probable Rapid Eye Movement Sleep Behavior Disorder (pRBD), restless leg syndrome (RLS), and insomnia in 2,466 Mexican, college-educated volunteers (32.5±12.4 years). The anonymous, online study applied the pRBD and RLS Single-Questions and self-reported night-time sleep duration, excessive daytime sleepiness, insomnia, and falls. Fall risk was strongly associated with pRBD and RLS. Subjects who fell at least once in the last year have an OR = 1.8137 [1.5352, 2.1426] of answering yes to pRBD and/or RLS questions, documented in 29% and 24% of volunteers, respectively. Subjects fell mostly outdoors (12:01 pm to 6:00 pm), 43% complained of early wake up hours, and 35% complained of sleep onset insomnia (EOI). EOI individuals have an OR of 2.5971 [2.1408, 3.1506] of answering yes to the RLS question. There is a robust association between falls, pRBD, and RLS, strongly suggesting misfolded proteinopathies involving critical brainstem arousal and motor hubs might play a crucial role. Nanoparticles are likely a significant risk for falls, sleep disorders, insomnia, and neurodegenerative lethal diseases, thus characterizing air particulate pollutants' chemical composition, emission sources, and cumulative exposure concentrations are strongly recommended.

The associations of cerebrospinal fluid biomarkers with cognition, and rapid eye movement sleep behavior disorder in early Parkinson's disease.

In Parkinson's disease (PD), levels of cerebrospinal fluid (CSF) biomarkers and progression of non-motor symptoms are associated, but the specifics are not yet clear. The aim of this study was to investigate the associations of non-motor symptoms with CSF biomarkers in PD. We assessed 487 individuals from the Parkinson's Progression Markers Initiative (PPMI), consisting of 155 healthy controls (HCs) and 332 individuals with PD. Patients with PD were grouped according to non-motor symptoms and compared CSF α-synuclein (α-syn), amyloid-beta 1-42 (Aβ1-42), and total tau (t-tau) levels. Multiple linear regressions were used in baseline analysis and linear mixed-effects models in longitudinal analysis. Analyses of mediating effects between cognition and CSF biomarkers were also performed. At baseline, PD patients with cognitive impairment (PDCI) exhibited significantly lower CSF α-syn (β = -0.1244; P = 0.0469), Aβ (β = -0.1302; P = 0.0447), and t-tau (β = -0.1260; P = 0.0131) levels than PD patients without cognitive impairment (PDCU). Moreover, a faster decline of α-syn (β = -0.2152; P = 0.0374) and Aβ (β = -0.3114; P = 0.0023) and a faster rise of t-tau (β = -0.1534; P = 0.0274) have been found in longitudinal analysis. The Aβ positive group showed an earlier decline in cognitive performance (β = -0.5341; P = 0.0180) compared with the negative Aβ group in both analyses. In addition, we found that PD patients with probable rapid eye movement sleep behavior disorder (pRBD) showed decreased CSF α-syn (β = -0.1343; P = 0.0033) levels. Finally, mediation analysis demonstrated that olfactory function partially mediated the relationship between cognition and CSF biomarkers levels. Our study shows that CSF biomarkers are associated with cognition at baseline and longitudinally. Cognitive impairment is more severe in patients with a heavier Aβ burden. CSF α-syn decreased in PD patients with pRBD. This study suggests that early recognition of the increased risk of non-motor symptoms is important for disease surveillance and may be associated with the pathological progression of CSF markers.

Different patterns of exosomal α-synuclein between Parkinson's disease and probable rapid eye movement sleep behavior disorder.

The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p &lt; 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p &lt; 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes. Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.

Diet Quality is Associated with Prodromal Parkinson's Disease Features in Chinese Adults.

The prodromal phase of Parkinson's disease (PD) is a critical window for prevention by modifying lifestyle factors. However, there is limited knowledge on how diet quality is associated with prodromal PD symptoms in Asian populations. To examine the association between overall diet quality and prodromal PD features. A total of 71,640 Chinese participants who were free of PD were included in this cross-sectional study. Diet quality was assessed using the modified Alternative Healthy Eating Index (mAHEI) and alternate Mediterranean Diet (aMED). Five prodromal features including probable rapid eye movement sleep behavior disorder (pRBD), hyposmia, excessive daytime sleepiness, constipation, and depressive symptom were measured using validated questionnaires. Logistic regression was used to calculate the odds ratio (OR) for having a combination of prodromal PD symptoms (1 and 2+ symptoms vs. 0 symptoms), adjusting for age, sex, lifestyle factors, total energy intake, and other potential confounders. In the multivariable-adjusted model, the OR for having 2+ versus 0 prodromal PD features was 0.64 (95% confidence interval [CI]: 0.49, 0.85) comparing the highest versus the lowest mAHEI diet quality quartiles with a significant inverse trend (P-trend=0.003). For individual prodromal PD features, better diet quality, as assessed by the mAHEI, was associated with lower odds of having excessive daytime sleepiness and constipation (P-trend < 0.05 for both). We observed a marginally significant association between aMED and prodromal PD features (adjusted OR comparing the extreme quartiles=0.74; 95% CI: 0.55, 0.98; P-trend=0.09). Better diet quality, as assessed by the mAHEI and the aMED, was associated with lower probability of having prodromal PD features in Chinese adults. © 2022 International Parkinson and Movement Disorder Society.

Brain Metabolic Correlates of Dopaminergic Denervation in Prodromal and Early Parkinson's Disease.

It remains unclear how brain metabolic activities transform in response to dopamine deficiency in the prodromal and early phases of Parkinson's disease (PD). To investigate the relationship between nigrostriatal dopaminergic denervation and brain glucose metabolism in patients with isolated rapid eye movement sleep behavior disorder (iRBD) and early PD. This cohort study included 28 patients with polysomnography-confirmed iRBD, 24 patients with de novo PD with probable rapid eye movement sleep behavior disorder (denovo PD), and 28 healthy controls (HCs) who underwent two positron emission tomography scans with 18 F-fluorodeoxyglucose (all participants) and 18 F-N-3-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)-nortropane (except for one denovo PD patient and 15 HCs). We analyzed striatal and voxel-wise whole-brain glucose metabolism in relation to nigrostriatal dopaminergic integrity and comparatively investigated the whole-brain metabolic connectivity among the groups. We also assessed longitudinal metabolic changes against progressive dopaminergic denervation over 4 years in the iRBD group. From HCs to iRBD and finally to the denovo PD, dopaminergic integrity positively correlated with metabolic activity in the caudate, whereas a negative correlation was observed in the posterior putamen. In the iRBD group, there was a metabolic increase in the inferior orbitofrontal cortex against putaminal dopaminergic denervation at baseline, but negative correlations were newly observed in the superior orbitofrontal cortex and superior frontal gyrus at the 4-year follow-up. The denovo PD group showed negative correlations in the cerebellum and fusiform gyrus. Intra- and inter-regional metabolic connectivities in the parieto-occipital cortices were enhanced in the iRBD group compared with the denovo PD and HC groups. In the iRBD group, overall metabolic connectivity was strengthened along with enhanced basal ganglia-frontal connection by advancing dopaminergic denervation. Our findings suggest diverse trajectories of metabolic responses associated with dopaminergic denervation between individual brain areas in the prodromal and early PD stages. © 2022 International Parkinson and Movement Disorder Society.

Association of Concurrent Olfactory Dysfunction and Probable Rapid Eye Movement Sleep Behavior Disorder with Early Parkinson's Disease Progression.

ABSTRACTBackgroundParkinson's disease (PD), with either rapid eye movement sleep behavior disorder (RBD) or olfactory dysfunction (OD), has been associated with disease progression. However, there is currently heterogeneity in predicting prognosis.ObjectivesTo identify whether the concurrent presence of OD and probable RBD (pRBD) in PD (Dual hit in PD, PD‐DH) is associated with disease progression.MethodsWe included 420 patients with de novo PD from the Parkinson's Progression Markers Initiative: 180 PD only (PD), 82 PD with OD (PD‐OD), 94 PD with pRBD (PD‐pRBD), and 64 PD with both OD and pRBD (PD‐DH). Participants underwent motor and nonmotor evaluations, dopamine transporter imaging, and cerebrospinal fluid (CSF) assessment. Data were analyzed with generalized estimating equations and Cox proportional hazards analysis.ResultsThe PD‐DH subtype was associated with higher scores and faster progression rates in Movement Disorder Society–Unified PD Rating Scale (MDS‐UPDRS) Parts II and III. Also, patients in PD‐DH group had faster deterioration in nonmotor symptoms, including MDS‐UPDRS Part I score, Montreal Cognitive Assessment, Hopkins Verbal Learning Test–Revised, Wechsler Memory Scale‐Third edition (WMS‐III) Letter Number Sequencing score, Symbol Digit Modalities Test, and Scales for Outcomes in PD–Autonomic scores, with all P values <0.002. Moreover, the PD‐DH subtype had a higher mild cognitive impairment risk (hazard ratio = 1.756, 95% confidence interval [CI] = 1.132–2.722; P = 0.012), faster decline in caudate standard uptake values (β = −0.03, 95% CI = −0.06 to −0.008, P = 0.012), and CSF α‐synuclein levels (β = −77, 95% CI = −149 to −5, P = 0.034) than the PD group.ConclusionCoexisting pRBD and OD in patients with PD may be associated with faster progressions in motor measurements and in cognitive and autonomic symptoms, indicating PD‐DH as a more aggressive subtype for PD.

Increased blood pressure variability is associated with probable rapid eye movement sleep behaviour disorder in elderly hypertensive patients

Purpose An increased blood pressure variability (BPV) has been reported to be associated with older age and cognitive dysfunction; however, associations between increased BPV and rapid eye movement sleep behaviour disorder (RBD) has not been thoroughly investigated in patients without clinical Lewy body diseases. Materials and methods In frailty outpatient clinic, we evaluated ambulatory BP, RBD screening questionnaire (RBDSQ), and beat-to-beat heart rate variability during positional change from sitting to standing in 112 elderly hypertensive patients. Results The mean age was 81.2 ± 6.3 years (68% male). There were 15 patients who had probable RBD (RBDSQ scores ≥ 5). Patients with RBD had a greater body mass index, coefficient of variation (CV) in 24-h diastolic BP (23.5 ± 6.1 versus 18.7 ± 5.8, p = 0.005), awake diastolic BP (23.0 ± 7.7 versus 18.6 ± 6.2, p = 0.017), and nocturnal systolic BP (14.9 ± 5.5 versus 12.0 ± 4.4, p = 0.025) compared with those without RBD, while systolic BP, diastolic BP, and cognitive function did not differ significantly between patients with and without RBD. Patients with RBD exhibited larger orthostatic BP fall compared with patients without RBD (−4.9 ± 11.0 versus 7.5 ± 11.8, p = 0.009) and lower CV of R–R intervals while standing (1.3 ± 0.6 versus 2.4 ± 1.5, p = 0.039). Multiple regression analysis revealed that patients with RBD had significantly greater CV of nocturnal systolic BP independent of age, sex, BMI, history of diabetes and dyslipidaemia, and use of antihypertensive drugs (p = 0.008). Conclusion An increased BPV in ambulatory BP, associated with autonomic dysfunction, can be observed in patients with probable RBD even in elderly patients without clinical presentation of Lewy body diseases.

Prediction of Quality of Life in Patients With Parkinson’s Disease With and Without Excessive Daytime Sleepiness: A Longitudinal Study

ObjectiveThere is a lack of longitudinal studies that directly compare the quality of life (QoL) and investigate the impact of clinical factors on QoL across different excessive daytime sleepiness (EDS) statuses in Parkinson’s disease (PD); therefore, we aimed to compare QoL and reveal the potential heterogeneous predictors of QoL between patients with PD with and without EDS.MethodsWe collected clinical data among 306 patients with PD over 2 years. EDS was assessed by the Epworth Sleepiness Scale and QoL was measured with the 39-item Parkinson’s Disease Questionnaire.ResultsWe found that at both baseline and follow-up, patients with PD with EDS had poorer QoL and suffered more non-motor symptoms including depression and clinical probable rapid eye movement sleep behavior disorder (cpRBD). The generalized linear mixed model analysis indicated that the major predictors of QoL in PD with EDS were the akinetic-rigid type, disease duration, and total levodopa equivalent dose, while in PD without EDS, the primary determinants of QoL were Hoehn and Yahr, Mini-Mental State Examination (MMSE), and cpRBD.ConclusionPatients with PD with EDS presented with poorer QoL. Besides, the baseline predictors of future QoL differed between patients with PD with and without EDS. These findings remind clinicians to target specific clinical factors when attempting to improve QoL among patients with PD.

Sleep and Autonomic Manifestations in Parkinson's Disease Complicated With Probable Rapid Eye Movement Sleep Behavior Disorder.

Patients with Parkinson’s disease (PD) complicated with rapid eye movement sleep behavior disorder (RBD) present with distinct clinical features. The purpose of this study was to determine the clinical features of sleep and autonomic symptoms in PD patients with probable RBD (pRBD). The study included 126 patients with PD. pRBD was defined as having a history of dream-enacting behavior with a total score of 5 or greater on the Japanese version of the RBD Screening Questionnaire (RBDSQ-J). The Parkinson’s Disease Sleep Scale-2 (PDSS-2) was used to evaluate sleep disturbances. Scales for Outcomes in Parkinson’s Disease-Autonomic dysfunction (SCOPA-AUT) were used to evaluate autonomic symptoms. Clinical assessments included disease severity, motor symptoms, olfaction, depression, cognitive function, levodopa equivalent dose (LED), and cardiac metaiodobenzylguanidine (MIBG) scintigraphy. Correlations between RBDSQ-J total scores and clinical variables were analyzed. Compared to PD patients without pRBD, PD patients with pRBD showed severe hyposmia, severe sleep-related symptoms, severe dysautonomia, and more reduced cardiac MIBG scintigraphy. Within the PDSS-2, the “PD symptoms at night” domain was significantly more severe in PD patients with pRBD. Within the SCOPA-AUT, the “urinary” and “cardiovascular” domains were significantly higher in PD patients with pRBD. In correlation analyses, RBDSQ-J total scores were positively correlated with PDSS-2 total scores, “PD symptoms at night” and “disturbed sleep” domains, Epworth Sleepiness Scale scores, SCOPA-AUT total scores, “urinary,” “cardiovascular,” and “thermo” domain scores, and LED. RBDSQ-J total scores were negatively correlated with cardiac MIBG scintigraphy uptake. Binary logistic regression analysis showed that PDSS-2 subitem 7 (distressing hallucinations) and SCOPA-AUT subitem 11 (weak stream of urine) were significant determinants for pRBD. Our study showed that PD patients with pRBD had characteristic sleep and autonomic symptoms.

Diffusion Tensor Imaging Reveals Deep Brain Structure Changes in Early Parkinson's Disease Patients with Various Sleep Disorders.

Parkinson’s disease (PD) is a progressive age-related movement disorder caused by dopaminergic neuron loss in the substantia nigra. Diffusion-based magnetic resonance imaging (MRI) studies—namely, diffusion tensor imaging (DTI)—have been performed in the context of PD, either with or without the involvement of sleep disorders (SDs), to deepen our understanding of cerebral microstructural alterations. Analyzing the clinical characteristics and neuroimaging features of SDs in early PD patients is beneficial for early diagnosis and timely invention. In our present study, we enrolled 36 early PD patients (31 patients with SDs and 5 patients without) and 22 healthy controls. Different types of SDs were assessed using the Rapid Eye Movement Sleep Behavior Disorder Questionnaire—Hong Kong, Epworth Sleepiness Scale, International Restless Legs Scale and PD Sleep Scale-2. Brain MRI examinations were carried out in all the participants, and a region-of-interest (ROI) analysis was used to determine the DTI-based fractional anisotropy (FA) values in the substantia nigra (SN), thalamus (Thal) and hypothalamus (HT). The results illustrate that SDs showed a higher prevalence in the early PD patients than in the healthy controls (86.11% vs. 27.27%). Early PD patients with nighttime problems (NPs) had longer courses of PD than those without (5.097 ± 2.925 vs. 2.200 ± 1.095; p < 0.05), and these patients with excessive daytime sleepiness (EDS) or restless legs syndrome (RLS) had more advanced Hoehn and Yahr stages (HY stage) than those without (1.522 ± 0.511 and 1.526 ± 0.513, respectively; both p < 0.05). Compared with the early PD patients without probable rapid eye movement sleep behavior disorder (pRBD), those with pRBD had longer courses, more advanced HY stages and worse motor and non-motor symptoms of PD (course(years), 3.385 ± 1.895 vs. 5.435 ± 3.160; HY stages, 1.462 ± 0.477 vs. 1.848 ± 0.553; UPDRS, 13.538 ± 7.333 vs. 21.783 ± 10.766; UPDRS, 6.538 ± 1.898 vs. 7.957 ± 2.345; all p < 0.05). In addition, the different number of SD types in early PD patients was significantly inversely associated with the severity of damage in the SN and HT. All of the early PD patients with various SDs had injuries in the SN, in whom the damage was more pronounced in patients with NP than those without. Moreover, early PD patients with NP, RLS or pRBD had worse degrees of HT damage than those without. The current study demonstrated the pathophysiological features and neuroimaging changes in early PD patients with various types of sleep disorders, which will help in early diagnosis and therapy.

The impact of probable rapid eye movement sleep behavior disorder on Parkinson's disease: A dual-tracer PET imaging study

ObjectiveWith a dual-tracer PET study design, this study aimed to identify the differences between PD patients with and without probable RBD (PD+RBD+/PD+RBD-) and the influence of timing of RBD onset [probable RBD anterior to PD onset (PD+RBDa)/probable RBD posterior to PD onset (PD+RBDp)]. MethodsSeventy-four PD+RBD+ patients, sixty-three PD+RBD-patients and twenty healthy controls were enrolled. Clinical variates, striatal DAT tracer uptake, voxel-wise glucose metabolism and Parkinson's disease-related pattern (PDRP) expressions were compared among groups. ResultsNo significant difference were found on clinical characteristics between PD+RBD+ and PD+RBD-groups. Compared with PD+RBD-group, PD+RBD+ group had more severe dopaminergic dysfunction (p<0.05) except for posterior putamen in the more affected hemisphere (MAH) (p = 0.350). Meanwhile, it showed relative hypermetabolism in anterior putamen in the less affected hemisphere (LAH), bilateral anterior pallidum with wider involvement in the LAH, hippocampus and para-hippocampus in the LAH and bilateral olfactory gyrus, together with relative hypometabolism in limited bilateral posterio-parietal area (p<0.001). Significantly elevated PDRP expression was also seen in PD+RBD+ group (p < 0.01). For the timing of RBD onset, PD+RBDa patients harbored greater progression rate than PD+RBDp patients (p<0.01), greater DAT declining rates of striatal subregions and greater increasing rate of PDRP expressions than both PD+RBDp and PD+RBD-patients (p<0.05). ConclusionOur study found that PD patients with probable RBD have worse striatal dopaminergic dysfunction and higher PDRP network activity, supporting the assumption that PD with RBD may be a specific phenotype of PD. Additionally, RBD preceding PD onset may indicate a steeper disease decline.

Imaging of the nigrostriatal system for evaluating the preclinical phase of Parkinson's disease development: the utility of neuromelanin, diffusion MRI, and DAT-SPECT.

To assess the utility of examining the nigrostriatal system with MRI and dopamine transporter (DAT) imaging for evaluating the preclinical phase of Parkinson's disease (PD). The subjects were 32 patients with early PD and a history of probable rapid eye movement sleep behavior disorder (RBD; PD group), 15 patients with idiopathic RBD (RBD group), and 24 age-matched healthy controls (HC group) who underwent neuromelanin and diffusion tensor MRI for analysis of the substantia nigra pars compacta (SNpc). The RBD and PD groups underwent DAT imaging. In the RBD group, totals of 39 MRI and 27 DAT imaging examinations were obtained longitudinally. For each value, intergroup differences and receiver operating characteristic analysis for diagnostic performance were examined statistically. The neuromelanin value was significantly lower and the diffusion tensor values except fractional anisotropy were significantly higher in the RBD and PD groups than in the HC group. The DAT specific binding ratio (SBR) was significantly lower in the PD group than in the RBD group. The areas under the receiver operating characteristic curves (AUCs) for neuromelanin/mean diffusivity value in the SNpc were 0.76/0.82 for diagnosing RBD and 0.83/0.80 for diagnosing PD. The area under the receiver operating characteristic curves for the SBR for discriminating PD from RBD was 0.87. MRI and DAT imaging may be useful for evaluating sequential nigrostriatal changes during the preclinical phase of PD. MRI detects nigrostriatal changes in both RBD and early PD, and DAT imaging detects nigrostriatal changes during the transition to PD in RBD.

The influence of probable rapid eye movement sleep behavior disorder and sleep insufficiency on fall risk in a community-dwelling elderly population

BackgroundThe objective was to investigate the individual effect and potential interactions of probable rapid eye movement sleep behavior disorder (pRBD) and sleep insufficiency on fall risk among a Chinese elderly population.MethodsCommunity-dwelling population aged 55 years or above were recruited from the Beijing Longitudinal Study on Aging II cohort from 2010 to 2011. Odds ratio (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression models. Multiplicative and additive interactions between pRBD and sleep insufficiency were examined using likelihood ratio tests and relative excess risk due to interaction (RERI), respectively.ResultsAmong 6891 included participants, 479 experienced at least once fall. pRBD and sleep insufficiency were both independently associated with elevated fall risk. Compared to the elderly without pRBD or sleep insufficiency, pRBD and sleep insufficiency was each associated with a 2.57-fold (OR = 2.57, 95%CI: 1.46–4.31) and 1.45-fold (OR = 1.45, 95%CI: 1.11–1.88) risk of falls individually, while their coexistence was associated with a less-than-additive 17% (OR = 1.17, 95%CI: 0.43–2.63) increased risk of falls. The combination of these two factors demonstrated evidence of a negative interaction on both multiplicative (ratio of ORs = 0.31, 95%CI: 0.10, 0.86) and additive (RERI = − 1.85, 95%CI: − 3.61, − 0.09) scale.ConclusionsOur study has provided robust evidence for the adverse effect of pRBD and sleep insufficiency, as well as their negative interaction on increasing fall risk in a Chinese elderly population.

Peripheral Clock System Abnormalities in Patients With Parkinson's Disease.

Objective: To evaluate the altered expression of peripheral clock genes, circulating melatonin levels, and their correlations with sleep-wake phenotypes including probable rapid eye movement sleep behavior disorder (pRBD) symptoms in a relatively large population of Parkinson’s disease (PD) patients.Methods: We determined the expression profiles of five principal clock genes, BMAL1, CLOCK, CRY1, PER1, and PER2, in the peripheral blood mononuclear cells (PBMCs) of PD patients (n = 326), and healthy controls (HC, n = 314) using quantitative real-time PCR. Melatonin concentration in the plasma of two groups was evaluated by enzyme-linked immunosorbent assay. Then we performed comprehensive association analyses on the PBMCs clock gene expression, plasma melatonin levels and sleep characteristics.Results: Our data showed that the expression levels of BMAL1, CLOCK, CRY1, PER1, and PER2 were significantly decreased in the PBMCs of PD as compared with that of HC (P < 0.05). PD patients had reduced plasma melatonin levels compared with HC (P < 0.0001). pRBD and excessive daytime sleepiness are common in these PD patients and are associated with the expression levels of all five clock genes (r = −0.344∼−0.789, P < 0.01) and melatonin concentration (r = −0.509∼−0.753, P < 0.01). Statistical analyses also revealed that a combination of five clock genes and melatonin could reach a high diagnostic performance (areas under the curves, 97%) for PD comorbid pRBD.Conclusion: This case-control study demonstrates that peripheral BMAL1, CLOCK, CRY1, PER1, PER2, and melatonin levels are altered in PD patients and may serve as endogenous markers for sleep and wakefulness disturbances of PD.

Sex differences in brain atrophy and cognitive impairment in Parkinson\u2019s disease patients with and without probable rapid eye movement sleep behavior disorder

BackgroundThe presence of rapid eye movement sleep behavior disorder (RBD) contributes to increase cognitive impairment and brain atrophy in Parkinson’s disease (PD), but the impact of sex is unclear. We aimed to investigate sex differences in cognition and brain atrophy in PD patients with and without probable RBD (pRBD).MethodsMagnetic resonance imaging and cognition data were obtained for 274 participants from the Parkinson's Progression Marker Initiative database: 79 PD with pRBD (PD-pRBD; male/female, 54/25), 126 PD without pRBD (PD-non pRBD; male/female, 73/53), and 69 healthy controls (male/female, 40/29). FreeSurfer was used to obtain volumetric and cortical thickness data.ResultsMales showed greater global cortical and subcortical gray matter atrophy than females in the PD-pRBD group. Significant group-by-sex interactions were found in the pallidum. Structures showing a within-group sex effect in the deep gray matter differed, with significant volume reductions for males in one structure in in PD-non pRBD (brainstem), and three in PD-pRBD (caudate, pallidum and brainstem). Significant group-by-sex interactions were found in Montreal Cognitive Assessment (MoCA) and Symbol Digits Modalities Test (SDMT). Males performed worse than females in MoCA, phonemic fluency and SDMT in the PD-pRBD group.ConclusionMale sex is related to increased cognitive impairment and subcortical atrophy in de novo PD-pRBD. Accordingly, we suggest that sex differences are relevant and should be considered in future clinical and translational research.

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.