Olfactory dysfunction in Parkinson disease and REM sleep behavior disorder

Olfactory dysfunction is an appealing biomarker for Parkinson disease (PD) because of the high prevalence (>90%) among PD patients and the relative ease of testing, as compared to other putative biomarkers such as neuroimaging of the dopamine system. Hyposmia develops during the early stages of PD and, therefore, may be one of the most sensitive markers for the early diagnosis of PD. Sniffin' Sticks, the University of Pennsylvania Smell Identification Test, and the Odor Stick Identification test for the Japanese, a short and simple nonlexical, olfactory identification test, can be useful for diagnosing PD and for discriminating between PD and other parkinsonian syndromes. REM sleep behavior disorder (RBD) is indicative of the development of neurodegenerative diseases involving synuclein pathology, including PD, multiple system atrophy, and dementia with Lewy bodies (DLB). Reduced odor identification was comparable in patients with PD, DLB, and RBD, but distinct from that in healthy subjects. Further, insights obtained from a deeper understanding of the pathophysiology of olfactory dysfunction in PD and RBD may lead to a deeper understanding of the mechanism underlying Lewy neurodegenerative diseases.     

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     

REM sleep behavior disorder in Parkinson disease: Association with abnormal ocular motor findings

BackgroundThe anatomical substrates associated with generalized muscle atonia during REM sleep are located on the pontine tegmentum and medial medulla oblongata. We examined whether patients with REM sleep behavior disorder (RBD) have abnormal ocular movements suggesting brainstem or cerebellar dysfunction in Parkinson's disease (PD).MethodsCross-sectional survey for the existence of RBD and abnormal ocular movements. Ocular movements were examined by video-oculography (VOG).ResultsA total of 202 patients were included in this study. One hundred and sixteen (57.4%) of the 202 patients have clinically probable RBD, and 28 (24.1%) of the 116 with clinically probable RBD patients had abnormal VOG findings suggesting brainstem or cerebellar dysfunction; whereas 86 of the 202 patients did not have clinically probable RBD, and only 7 (8.1%) of the 86 patients had abnormal VOG findings suggesting brainstem or cerebellar dysfunction (P = 0.001).ConclusionThis study suggests that the presence of RBD is associated with more severe or extensive brainstem pathology or different distribution of pathology in PD.     

Heart rate variability in Parkinson disease and idiopathic REM sleep behavior disorder

Purpose

Heart rate variability, a marker of autonomic function modulation, is known to be blunted in Parkinson disease, although data remains conflicting and a putative modifying role of REM sleep behavior disorder persists unclarified.

Methods

We assessed ten patients with idiopathic REM sleep behavior disorder patients, 18 patients with Parkinson disease and REM behavior disorder and eight patients with Parkinson disease without REM sleep behavior disorder. Heart rate variability analysis was performed in 5-min epochs selected from wake, Non-REM and REM polysomnography records. We compared heart rate variability measures by stage between two sets of groups: Parkinson disease vs. idiopathic RBD and patients with vs. without RBD, by using repeated measures ANOVA.

Results

There were no heart rate variability differences between Parkinson disease and idiopathic REM sleep behavior disorder groups. There were significant stage vs. group interactions (p?=?0.045) regarding the high frequencies components when comparing patients with and without REM sleep behavior disorder, with the former presenting lower values and attenuation of sleep stage variations.

Conclusion

Our study suggests that RBD is related with reduction in parasympathetic modulation of heart rate variability and blunting of sleep stage related variations.

     

Subtle gait changes in patients with REM sleep behavior disorder

Many people with rapid eye movement (REM) sleep behavior disorder (RBD) have an underlying synucleinopathy, the most common of which is Lewy body disease. Identifying additional abnormal clinical features may help in identifying those at greater risk of evolving to a more severe syndrome. Because gait disorders are common in the synucleinopathies, early abnormalities in gait in those with RBD could help in identifying those at increased risk of developing overt parkinsonism and/or cognitive impairment. We identified 42 probable RBD subjects and 492 controls using the Mayo Sleep Questionnaire and assessed gait velocity, cadence, and stride dynamics with an automated gait analysis system. Cases and controls were similar in age (79.9 ± 4.7 and 80.1 ± 4.7, P = 0.74), Unified Parkinson's Disease Rating Scale Part III (UPDRS) score (3.3 ± 5.5 and 1.9 ± 4.1, P = 0.21) and Mini–Mental State Examination scores (27.2 ± 1.9 and 27.7 ± 1.6, P = 0.10). A diagnosis of probable RBD was associated with decreased velocity (?7.9 cm/s; 95% confidence interval [CI], ?13.8 to ?2.0; P < 0.01), cadence (?4.4 steps/min; 95% CI, ?7.6 to ?1.3; P < 0.01), significantly increased double limb support variability (30%; 95% CI, 6–60; P = 0.01), and greater stride time variability (29%; 95% CI, 2–63; P = 0.03) and swing time variability (46%; 95% CI, 15–84; P < 0.01). Probable RBD is associated with subtle gait changes prior to overt clinical parkinsonism. Diagnosis of probable RBD supplemented by gait analysis may help as a screening tool for disorders of α‐synuclein. © 2013 International Parkinson and Movement Disorder Society     

Longitudinal changes in cognition in early Parkinson's disease patients with REM sleep behavior disorder

IntroductionCognitive decline is common in Parkinson's disease (PD), and identifying patients at highest risk for it is essential. We aimed to examine the effect of possible REM sleep behavior disorder (pRBD) on rate of cognitive decline in early PD, for both global cognition and in specific cognitive domains.MethodsParkinson's Progression Markers Initiative (PPMI) is a multi-site, international study of PD patients untreated at enrollment. pRBD was assessed with the REM sleep behavior disorder questionnaire (RBDSQ). Global cognition was assessed at baseline and annually using the Montreal Cognitive Assessment (MoCA) and a cognitive battery. Linear mixed effects models were used to examine the relationship between pRBD (RBDSQ ≥ 6) and rate of change in cognitive variables. Age, sex, years of education, and baseline motor and cognitive scores were included as covariates.ResultsThe baseline sample consisted of 423 individuals with PD, mean age 61.7 years and 65.5% male. Data was available on 389, 366, and 196 participants at 1-year, 2-year, and 3-year follow-up respectively. Possible RBD occurred in 108 (25.5%) at baseline. In multivariate analyses, baseline RBD was associated with greater annual rate of decline in MoCA score (β = −0.34, 95%CI −0.54, −0.13, p < 0.001), Symbol Digit Modalities Test (β = −0.69, 95%CI −1.3, −0.09, p = 0.024), and Hopkins Verbal Learning Test-Revised, delayed free recall (β = −0.21, 95%CI −0.41, −0.013, p = 0.037).ConclusionsPossible RBD is common in early PD and predicts future cognitive decline, particularly in attention and memory domains.     

Factors related to clinically probable REM sleep behavior disorder in Parkinson disease

Rapid eye movement sleep behavior disorder (RBD) is commonly accompanied in Parkinson disease (PD). However, the underlying mechanism linking RBD to PD remains unclear. We interviewed and examined 447 consecutive patients with PD to investigate factors associated with the presence of RBD in PD patients. Using the minimal diagnostic criteria for parasomnias provided in the International Classification of Sleep Disorders-Revised (ICSD-R), 164 patients (36.5%) were diagnosed with clinically probable RBD (cpRBD). PD patients with cpRBD were older, had a longer duration of PD, a more severe level of disability, a longer duration of antiparkinsonian medication, and a lower proportion of their Unified Parkinson Disease Rating Scale (UPDRS) scores accounted for by tremor than those without RBD. Multivariate and univariate logistic regression analyses revealed that patient age, PD symptom duration (and, accordingly, more severe motor disability), tremor score, and proportion of the UPDRS score accounted for by tremor were significant factors associated with the presence of RBD in PD patients. The results of the present study support previous observations that PD with RBD may result from a different underlying pattern of neurodegeneration than PD without RBD.     

REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease

OBJECTIVE: To determine the frequency of REM sleep behavior disorder (RBD) among patients with PD using both history and polysomnography (PSG) recordings and to further study REM sleep muscle atonia in PD. BACKGROUND: The reported occurrence of RBD in PD varies from 15 to 47%. However, no study has estimated the frequency of RBD using PSG recordings or analyzed in detail the characteristics of REM sleep muscle atonia in a large group of unselected patients with PD. METHODS: Consecutive patients with PD (n = 33) and healthy control subjects (n = 16) were studied. Each subject underwent a structured clinical interview and PSG recording. REM sleep was scored using a method that allows the scoring of REM sleep without atonia. RESULTS: One third of patients with PD met the diagnostic criteria of RBD based on PSG recordings. Only one half of these cases would have been detected by history. Nineteen (58%) of 33 patients with PD but only 1 of 16 control subjects had REM sleep without atonia. Of these 19 patients with PD, 8 (42%) did not present with behavioral manifestations of RBD, and their cases may represent preclinical forms of RBD associated with PD. Moreover, the percentage of time spent with muscle atonia during REM sleep was lower among patients with PD than among healthy control subjects (60.1% vs 93.2%; p = 0.003). CONCLUSIONS: RBD and REM sleep without atonia are frequent in PD as shown by PSG recordings.     

Regional cerebral blood flow changes in patients with idiopathic REM sleep behavior disorder

Background: Recent studies have shown an association between rapid eye movement sleep behavior disorder (RBD) and neurodegenerative disorders, especially alpha‐synucleinopathies. Objective: We investigated regional cerebral blood flow (rCBF) changes using single photon emission computed tomography (SPECT) in patients with idiopathic RBD (iRBD), to determine functional brain alterations associated with the disorder. Methods: The SPECT data of 24 patients with iRBD were compared with those of 18 age‐matched normal controls using statistical parametric mapping 2. Results: We found decreased rCBF in the parietooccipital lobe (precuneus), limbic lobe, and cerebellar hemispheres in patients with iRBD, which is commonly seen in patients with Lewy body disease (Parkinson’s disease and dementia with Lewy bodies) or multiple system atrophy. Conclusion: Our SPECT study suggests that iRBD can be a presymptomatic stage of alpha‐synucleinopathies.     

The relation between abnormal behaviors and REM sleep microstructure in patients with REM sleep behavior disorder

ObjectiveTo investigate the temporal relation between rapid eye movement (REM) sleep microstructure (REMs, EMG activity) and motor events in REM sleep behavior disorder (RBD).MethodsPolysomnographic records of eight patients with RBD were analyzed and compared with those of eight sex- and age-matched controls. We examined sleep microstructure for REM sleep with and without REMs and phasic chin EMG activity and their temporal relation to motor events on video.ResultsAll types of motor events were either more frequent in RBD patients than in controls (P ? 0.007) or present solely in RBD patients. In RBD, major motor events were significantly more frequent during REM sleep with REMs than during REM sleep without REMs (violent, 84.0% vs. 16.0%, P < 0.001; complex/scenic behavior, 78.1% vs. 23.2%, P < 0.001; major jerks, 77.5% vs. 20.3%, P < 0.001), whereas minor motor activity was evenly distributed (54.1% vs. 45.9%, P = 0.889). Controls showed predominantly minor motor activity with rare myoclonic body jerks. The distribution of motor events did not differ between REM sleep with and without REMs (40.9% vs. 59.1%, P = 0.262).ConclusionsIn RBD, major motor activity is closely associated with REM sleep with REMs, whereas minor jerks occur throughout REM sleep. This finding further supports the concept of a dual nature of REM sleep with REMs and REM sleep without REMs and implies a potential gate control mechanism of REM sleep with REMs for the manifestation of elaborate or violent behaviors in RBD.     

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.     

帕金森病患者快速眼动期睡眠行为障碍的多项睡眠图分析

目的:客观地分析帕金森病(PD)患者快速眼动期睡眠行为障碍(RBD)的多项睡眠图(PSG)表现.方法:采用UPDRS -Ⅲ评分、Hoehn -Yahr评分及用药调查表分别对28例PD患者的疾病严重程度、病程、多巴胺能药物应用等情况进行评定和计算,并结合全夜可移动的同步视频多项睡眠图(V-PSG)监测进行分析比较各项睡眠结构、睡眠进程以及睡眠相关事件.结果:利用同步V-PSG并结合临床病史,发现28例PD患者中有14例(占50%)伴有RBD.PD伴RBD组的病程[(6.76±3.44)年]较PD不伴RBD组病程[(2.96±1.99)年]长,其Hoehn -Yahr评分为(3.21±0.89)、非快速眼动(NREM)睡眠1期(N1)百分比[(23.56%±13.64)%]、醒觉指数[(54.41±36.45)次/h]、睡眠期周期性腿动指数(5.9次/h)较PD不伴RBD组的相应值[(2.21±0.80)、(11.47%±7.34)%、(26.55±17.25)次/h、1.5次/h]明显升高(P<0.05);而两组患者间的UPDRS -Ⅲ评分、左旋多巴等效剂量、睡眠效率、N2、N3、REM睡眠期百分比及呼吸暂停低通气指数等比较差异无统计学意义.14例PD伴RBD患者中有3例(占21%)出现相关睡眠致伤.结论:同步V-PSG结合临床病史可以提高RBD诊断的准确性.PD伴RBD患者可影响部分睡眠结构,还可能存在相关睡眠致伤的风险.     

REM sleep behavior disorder in Parkinson's disease and dementia with Lewy bodies

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. Patients appear to "act out their dreams," in which the exhibited behaviors mirror the content of the dreams. Management of RBD involves counseling about safety measures in the sleep environment; in those at risk for injury, clonazepam and/or melatonin is usually effective. In this article, the authors present a detailed review of the clinical and polysomnographic features, differential diagnosis, diagnostic criteria, management strategies, and pathophysiologic mechanisms of RBD. They then review the literature and their institutional experience of RBD associated with neurodegenerative disease, particularly Parkinson's disease and dementia with Lewy bodies. The evolving data suggests that RBD may have clinical diagnostic and pathophysiologic significance in isolation and when associated with neurodegenerative disease.