The prospective memory of patients with idiopathic REM sleep behavior disorder

BackgroundIdiopathic rapid eye movement sleep behavior disorder (iRBD) likely represents the prodromal stage of synucleinopathy. The present study was to investigate if there was prospective memory (PM) impairment and the relationship between different PM tasks and traditional cognitive tests in patients with iRBD.MethodsA total of 28 patients with iRBD, 25 with Parkinson's disease (PD) and 21 healthy controls were included. The Cambridge Prospective Memory Test (CAMPROMPT) was used to measure the PM including time-based (TBPM) and event-based PM (EBPM). Standard cognitive tests were administered to all participants.ResultsEBPM scores were lower only in patients with iRBD, while the obvious PM abnormalities were found in patients with PD. The patients with iRBD and PD performed worse on delayed recall of the Rey Auditory Verbal Learning Test (RAVLT) and copy of the Rey–Osterrieth complex figure (ROCF). The EBPM correlated with attention, executive function, and immediate memory besides working memory in patients with iRBD. The PM tasks involved in more memory functions in PD patients.ConclusionsThe patients with iRBD were impaired on both episodic memory and EBPM tasks that correlated with attention, executive function, and immediate memory. The PM abnormality was an early cognitive change in iRBD to which more attention should be paid more attention.     

The Montreal Cognitive Assessment: A screening tool for mild cognitive impairment in REM sleep behavior disorder

Mild cognitive impairment (MCI) is a frequent feature in idiopathic REM sleep behavior disorder (RBD), a sleep disturbance that can be a preclinical stage of Parkinson's disease or Lewy body dementia. We evaluated the sensitivity and specificity of two brief screening tools, the Montreal Cognitive Assessment (MoCA) and the Mini‐Mental State Examination (MMSE), in detecting MCI in idiopathic RBD. Thirty‐eight idiopathic RBD patients underwent a comprehensive neuropsychological assessment, including the MoCA and the MMSE. Receiver operating characteristic curves were created for the MoCA and the MMSE to assess their ability to identify MCI in idiopathic RBD patients, with neuropsychological assessment as the gold standard. For the MoCA, a normality cutoff of 26 yielded the best balance between sensitivity (76%) and specificity (85%) with a correct classification of 79%. For the MMSE, the optimal normality cutoff was 30, with a sensitivity of 84% and a specificity of 54% and a correct classification of 74%. The MoCA is superior to the MMSE in detecting MCI in idiopathic RBD patients, showing good sensitivity and very good specificity. © 2010 Movement Disorder Society     

REM sleep behavior disorder, hallucinations, and cognitive impairment in Parkinson's disease.

The objective of this study was to evaluate the relationship between REM sleep behavior disorder (RBD), hallucinations, and cognitive impairment in Parkinson's disease (PD). One hundred and ten PD patients, divided into three groups (without RBD or hallucinations; with RBD but no hallucinations; with RBD and hallucinations), were submitted to neuropsychological evaluation. The group without RBD and hallucinations showed normal neuropsychological tests when compared to normal controls. The group with hallucinations was characterized by a more severe cognitive impairment affecting both short- and long-term memory, logical abilities, and frontal functions, while the RBD-only group presented frontal impairment. The hypothesis that RBD in PD can be considered a risk factor not only of the hallucinations but also of more severe and diffuse cognitive abnormalities needs to be strengthened through a longitudinal evaluation.     

Mild cognitive impairment and abnormal brain metabolic expression in idiopathic REM sleep behavior disorder

BackgroundMild cognitive impairment (MCI) is a common feature of isolated rapid-eye-movement sleep behavior disorder (iRBD). Here, we assessed cognitive functions and MCI in a prospective iRBD cohort and investigated their association with disease-specific brain metabolic patterns.MethodsForty-four patients with polysomnography-confirmed iRBD performed a standardized battery of neuropsychological examinations every two years. We used previously established spatial covariance patterns from de novo drug-naïve Parkinson's disease with concomitant RBD (_denovoPDRBD-RP) and iRBD (iRBD-RP) using ¹⁸F-fluorodeoxyglucose PET scan. We compared those expressions between iRBD with normal cognition (iRBD-NC) and with mild cognitive impairment (iRBD-MCI), and evaluated whether they predict progressive cognitive deterioration.ResultsTwenty iRBD patients (45 %) had MCI at baseline and 12 patients (27 %, about 7 % per year) had clinically significant cognitive deterioration after 4 years. The iRBD-MCI and iRBD-NC groups showed similar rates of cognitive change, but iRBD-MCI consistently performed worse in the domains of verbal memory and executive function. Elevated _denovoPDRBD-RP expression predicted cognitive deterioration (hazard ratio = 5.98 [1.70–21.06]), whereas iRBD-RP did not.ConclusionsIncreased disease-specific brain metabolic patterns are associated with iRBD-MCI and impending cognitive deterioration with the risk of progression to Lewy body dementia.     

The fate of patients with REM sleep behavior disorder and mild cognitive impairment

ObjectiveTo investigate clinical and dopaminergic pre-synaptic brain imaging characteristics of subjects with idiopathic rapid eye movement (REM) behavior disorder (iRBD) and mild cognitive impairment (MCI), and to evaluate the combined predictive value of risk factors for short-term conversion to synucleinopathy.MethodIn sum, 44 polysomnography (PSG)-confirmed iRBD patients (68.5 ± 7.2 years; 38 males) underwent ¹²³I-FP-CIT-SPECT, comprehensive neuropsychological evaluation, clinical examination and clinical follow-up every six months (30.6 ± 21.5 months). Step-wise logistic regression was applied to identify those features discriminating iRBD patients with (iRBD-MCI; n = 14) and without MCI (normal cognition [NC], iRBD-NC; n = 30). The risk of neurodegeneration was estimated with Kaplan–Meier analysis. Predictors of phenoconversion were assessed with Cox proportional-hazards analysis, adjusting for age, gender and education. A generalized linear model (GLM) was applied to define the best combination of risk factors predicting conversion at follow-up.ResultsAt baseline, patients with iRBD-MCI showed reduced striatal dopamine transporter (DAT) specific to non-displaceable binding ratio (SBR) and more constipation compared with iRBD-NC patients (p < 0.0001). During the follow-up, 10 patients (22.7%) develop an overt synucleinopathy. GLM analysis showed that patients with orthostatic hypotension, non-motor experiences of daily living, reduced putaminal DAT-SPECT SBR, and cognitive impairment in verbal memory/visuoconstruction abilities were at higher risk of phenoconversion (Hazard Ratio [HR] 26.05; Sensitivity 90%; Specificity 100%; Accuracy 97.73%; Positive Predictive Value 100%; Negative Predictive Value 97.14%).ConclusionsiRBD-MCI patients showed a more severe dopaminergic neuroimaging and clinical phenotype. Combining clinical and neuroimaging markers allowed to achieve excellent ability in identifying iRBD patients at high risk of developing a synucleinopathy within about three years from diagnosis.     

Observations on muscle activity in REM sleep behavior disorder assessed with a semi-automated scoring algorithm

Objectives

Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by dream enactment due to a failure of normal muscle atonia. Visual assessment of this muscle activity is time consuming and rater-dependent.

Electroencephalogram slowing in rapid eye movement sleep behavior disorder is associated with mild cognitive impairment

Background

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a well-documented risk factor for synucleinopathies such as Parkinson disease (PD) and dementia with Lewy bodies (DLB). Moreover, approximately 50% of iRBD patients have mild cognitive impairment (MCI). The purpose of our study was to investigate waking electroencephalogram (EEG) abnormalities specific to iRBD patients with MCI.

Methods

Forty-two polysomnographically confirmed iRBD patients, including 23 iRBD [+]MCI patients 19 patients without MCI (iRBD [−]MCI), and 37 healthy subjects participated in the study. All participants underwent a complete neuropsychologic assessment for MCI diagnosis and a waking quantitative EEG recording.

Results

iRBD [+]MCI patients had a higher slow-to-fast frequency ratio than iRBD [−]MCI patients and controls in the parietal, temporal, and occipital regions. iRBD [+]MCI patients also had higher relative θ power in the parietal, temporal, and occipital regions and lower relative α power in the occipital region compared to iRBD [−]MCI patients and controls. Moreover, iRBD [+]MCI patients had higher relative θ power in the frontal and central areas and lower relative β power in the central, parietal, and temporal regions compared to controls. The dominant occipital frequency also was slower in iRBD [+]MCI patients compared to controls. No between-group differences were observed between iRBD [−]MCI patients and controls.

Conclusion

In iRBD patients, only those with concomitant MCI showed waking EEG slowing in the posterior cortical regions, providing a potential marker for an increased risk for developing DLB or PD.     

Cardiac autonomic dysfunction in idiopathic REM sleep behavior disorder

More than 50% of persons with idiopathic REM sleep behavior disorder (RBD) will develop Parkinson's disease or Lewy body dementia. Symptom screens and metaiodobenzylguanine (MIBG)‐scintigraphy suggest autonomic abnormalities in idiopathic RBD, but it is unclear whether autonomic abnormalities can predict neurodegenerative disease. From a cohort of 99 patients with idiopathic RBD, we selected those who developed parkinsonism or dementia. These were matched by age, sex, and follow‐up duration to patients with RBD who remained disease free and to matched controls. From the polysomnographic trace performed at baseline evaluation, measures of beat‐to‐beat RR variability including time domains (mean RR‐interval and RR‐standard deviation) and frequency domains (low and high frequency components) were retrospectively assessed. Twenty‐one patients with idiopathic RBD who developed neurodegenerative disease were included (Parkinson's disease‐11, multiple system atrophy‐1, and dementia‐9). Age at PSG was 66 years, and 86% were male. PSG was performed on average 6.7 years before defined neurodegenerative disease. Comparing all patients with idiopathic RBD to controls, there were significant reductions in RR‐standard deviation (24.6 ± 2.2 ms vs. 35.2 ± 3.5 ms, P = 0.006), very low frequency components (238.6 ± 99.6 ms² vs. 840.1 ± 188.3 ms², P < 0.001), and low frequency components (127.8 ± 26.3 ms² vs. 288.7 ± 66.2 ms², P = 0.032). However, despite clear differences between patients with idiopathic RBD and controls, there were no differences in any measure between those who did or did not develop disease. RR‐variability analysis demonstrates substantial autonomic dysfunction in idiopathic RBD. However, this dysfunction is identical in patients who will or will not develop defined neurodegenerative disease. This suggests that autonomic dysfunction is linked with RBD independent of associated Parkinson's disease or Lewy body dementia. © 2010 Movement Disorder Society     

帕金森病患者快速眼球运动睡眠行为障碍的回顾分析及前瞻性研究

目的 临床回顾分析帕金森病(PD)患者快速眼球运动(REM)睡眠行为障碍(RBD)的发生率及其危险因素,前瞻性研究RBD对PD进展的影响.方法 根据国际睡眠障碍分型修订版(ICSD-R)关于RBD的最低诊断标准,对符合临床疑似RBD(cpRBD)的患者进行统一PD评估量表(UPDRS)、MMSE、蒙特利尔认知功能评估量表(MoCA)等测定与随访观察,随访时间为2.5年.结果 基线时cpRBD的发生率为35.6%(47/132),随访末的发生率为41.7%(55/132),脱落率为11.4%(15/132).RBD的独立危险因素为MoCA分值低(OR=0.817,P=0.004),而震颤型起病形式为RBD的保护因素(OR=0.247,P=0.020).cpRBD患者病情进展较非cpRBD患者快[UPDRSⅢ终点与基线差值:(9.86±4.96)分与(6.76±4.26)分,t=2.909,P=0.005;H-Y分期终点与基线差值:(0.77±0.54)期与(0.33±0.49)期,t=3.664,P=0.000].结论 RBD的发生可能预测PD病情的快速进展、认知功能损害、精神症状的出现.     

Effects of safinamide on REM sleep behavior disorder in Parkinson disease: A randomized,longitudinal, cross-over pilot study

BackgroundRapid Eye Movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during REM-sleep. RBD as a premotor feature occurred souvent in patients who develop Parkinson’s disease. The glutamatergic, glycinergic, and GABA-ergic systems appear to play a crucial role in the pathogenesis of RBD.MethodsThe present exploratory longitudinal cross-over study aimed to observe the effect of safinamide on RBD symptoms. Thirty patients with PD and RBD were randomized into two groups (15 subjects each), those that received for a period of 3-months safinamide (50 mg/die) in addition (Group A + ) or in absence (Group B − ) to the usual antiparkinsonian therapy. Patients exploring the clinical and video-polysomnographic changes occurred during this pharmacological therapy.ResultsTwenty-two of 30 patients reported clear improvement in symptoms during safinamide treatment, and 16 were absolutely free from clinical RBD-symptoms at the end of the treatment. Eight patients reported slight improvement in RBD-symptoms. In 6/30 patients no substantial improvement was recorded about clinical RBD-symptoms had frightening dreams or from the bed after 1-week of treatment. In addition, after safinamide, the mean UPDRS-II and III scores decreased, while PDSS-2 score indicating an improvement in both motor symptoms and nocturnal sleep features. A significant reduction of sleep behavior disorder by questionnaire-Hong Kong-score (RBDQ-HS), mainly for two individual RBDQ-HK-items (dream related movements and failing out of bed) was registered.ConclusionsThis pilot study indicated that safinamide is well tolerated and improves RBD-symptom in parkinsonian.     

Testosterone not associated with violent dreams or REM sleep behavior disorder in men with Parkinson's.

We examined the relationship between testosterone levels, violent dreams, and REM sleep behavior disorder (RBD) in 31 men with Parkinson's disease (PD): 12 with clinical RBD and 19 without. All PD patients with clinical RBD experienced violent dreams, but none of the 19 non-RBD patients reported violent dreams. While dream content appears to be more aggressive in PD patients with clinical RBD, the presence of violent dreams or clinical RBD is not associated with testosterone levels in men with PD.     

Video analysis of motor events in REM sleep behavior disorder.

In REM sleep behavior disorder (RBD), several studies focused on electromyographic characterization of motor activity, whereas video analysis has remained more general. The aim of this study was to undertake a detailed and systematic video analysis. Nine polysomnographic records from 5 Parkinson patients with RBD were analyzed and compared with sex- and age-matched controls. Each motor event in the video during REM sleep was classified according to duration, type of movement, and topographical distribution. In RBD, a mean of 54 +/- 23.2 events/10 minutes of REM sleep (total 1392) were identified and visually analyzed. Seventy-five percent of all motor events lasted <2 seconds. Of these events, 1,155 (83.0%) were classified as elementary, 188 (13.5%) as complex behaviors, 50 (3.6%) as violent, and 146 (10.5%) as vocalizations. In the control group, 3.6 +/- 2.3 events/10 minutes (total 264) of predominantly elementary simple character (n = 240, 90.9%) were identified. Number and types of motor events differed significantly between patients and controls (P < 0.05). This study shows a very high number and great variety of motor events during REM sleep in symptomatic RBD. However, most motor events are minor, and violent episodes represent only a small fraction.     

Follow-up study of cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder

Background: Cardiac ¹²³I‐metaiodobenzylguanidine (¹²³I‐MIBG) uptake in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is markedly reduced, as in Parkinson’s disease (PD). Methods: We performed ¹²³I‐MIBG scintigrams on patients with iRBD and PD. After the initial ¹²³I‐MIBG scintigram, we retested subjects after a mean of 2.8 years. Results: The delayed heart‐to‐mediastinum (H/M) ratio of cardiac ¹²³I‐MIBG uptake was not significantly reduced between the first and second study in either group (P = 0.050, P = 0.091, respectively) . Follow‐up imaging revealed a mean decline of 4.21 ± 9.06% or 6.40 ± 19.02% in the delayed H/M ratio in those with iRBD or PD, respectively. Conclusions: The ¹²³I‐MIBG uptake findings might indicate progression early in the course of iRBD or PD, but the progression is heterogeneous and independent of development of motor symptoms.     

Relationship between visual hallucinations and REM sleep behavior disorder in patients with Parkinson's disease

OBJECTIVES: REM sleep behavior disorder (RBD) has been documented to precede or to co-occur with Parkinson's disease (PD). Parkinson's disease is one of the most common neurological conditions associated with visual hallucinations. Cognitive dysfunction is present in PD, even at the early stages of these diseases. In this study we aimed to investigate the relationship between visual hallucinations and RBD in patients with idiopathic Parkinson's disease (IPD). Additionally, we evaluated the association of the cognition and the pattern of cognitive impairment with VHs and RBD, effects of factors like duration and severity of the disease and duration of levodopa usage. PATIENTS AND METHODS: Seventy-nine patients, diagnosed as PD, were included the study and then, patients were divided into four groups; with RBD and VHs (group 1), with RBD but no VHs (group 2), with VHs but no RBD (group 3), without RBD and VHs (group 4). We compared each group with the others according to demographic characteristics and neuropsychological test scores. RESULTS: Of all patients, in 46% (n=36) RBD and in 48% (n=38) VHs were observed. Our study established VHs in 58% of patients with RBD, and RBD in 55% of patients with VHs. However, due to a 40% incidence of VHs in patients without RBD, RBD and VHs were not found to be correlated. All of the neuropsychometric test scores did not reveal significant difference between groups. CONCLUSION: Although it seems like there is a small association between RBD and VHs in our patients, it was not significant. Group 1 presented with significantly worse scores in UPDRS total scores and I, II subscores.     

Manifestations of Parkinson disease differ in association with REM sleep behavior disorder

REM sleep behavior disorder (RBD) is commonly associated with Parkinson disease (PD), but it is unclear whether this association has implications for disease manifestations. We evaluated 36 PD patients for the presence of RBD by polysomnography. Patients underwent an extensive evaluation by a movement disorders specialist blinded to polysomnography results. Severity of motor manifestations, autonomic, visual, psychiatric, and olfactory dysfunctions and quality of life (QOL) were assessed, and compared using regression analysis that adjusted for disease duration, age and sex. Severity of motor manifestations did not differ between groups. However, the presence of RBD in PD was strongly associated with symptoms and signs of orthostatic hypotension (systolic blood pressure lying to standing = ?25.7 ± 13.0 mmHg vs. ?4.9 ±14.1, P < 0.001); and orthostatic symptom prevalence = 71% vs. 27%, P = 0.0076). There was no association between RBD and other autonomic symptoms. Color vision was worse in patients with RBD, but olfactory dysfunction did not differ between groups. The prevalence of depression, hallucinations, paranoia, and impulse disorders did not differ between groups. Emotional functioning and general health QOL measures were lower in those with RBD, but there were no differences between groups on disease‐specific indices or on measures of overall physical QOL. These findings suggest that the pathophysiology of RBD and nonmotor manifestations of PD, particularly autonomic dysfunction, are linked. © 2008 Movement Disorder Society