Characteristics of sleep disturbances in Japanese patients with Parkinson's disease. A study using Parkinson's disease sleep scale

The present multicenter cross‐sectional study was performed using semistructured questionnaires to determine the contributing factors of sleep disturbances in Japanese patients with Parkinson's disease (PD). We used the Parkinson's disease sleep scale (PDSS, Japanese version). All data were obtained by means of interviewed questionnaire and physical examination by neurologists. The study was carried out between April 2005 and December 2005 at eight university hospitals and affiliated facilities in the Kanto area of Japan. A total of 188 (85 men and 103 women) PD patients and 144 controls (64 men and 80 women) were included. Stepwise regression analysis identified complications of treatment, depression, age, and disease duration as significant risk factors of sleep disturbances in PD. Significant differences in total PDSS score were observed between Hoehn & Yahr (H&Y) Stages 1 and 4, between H&Y Stages 2 and 4, and between H&Y stages 3 and 4 (Bonferroni test). The results of this survey suggested that complications due to treatment (dyskinesia, wearing off, on–off), depressive state, and disease stage are significant determinants of sleep disorders in Japanese patients with PD. We speculate that the reduction of neurotransmitters involved in the sleep–wakefulness mechanism and degeneration of neurons progress together in parallel with deterioration of motor function. © 2006 Movement Disorder Society     

Melatonin for sleep disturbances in Parkinson's disease

BACKGROUND AND PURPOSE: Many patients with Parkinson's disease (PD) experience sleep-related symptoms. Studies in other populations indicate that melatonin can increase sleep efficiency, decrease nighttime activity, and shorten sleep latency, but there has been little research on the use of melatonin in PD. The purpose of this study was to compare the effects of two doses of melatonin to placebo on sleep, daytime sleepiness, and level of function in patients with PD who complained of sleep disturbances. PATIENTS AND METHODS: A multi-site double-blind placebo-controlled cross-over trial was employed; 40 subjects completed the 10-week protocol. There was a 2-week screening period, 2-week treatment periods, and 1-week washouts between treatments. Nocturnal sleep was assessed by actigraphy and diaries, whereas daytime sleepiness and function were assessed by the Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS), and General Sleep Disturbance Scale (GSDS). RESULTS: Repeated measures analysis of variance revealed a significant improvement in total nighttime sleep time during the 50 mg melatonin treatment compared to placebo. There was significant improvement in subjective sleep disturbance, sleep quantity, and daytime sleepiness during the 5 mg melatonin treatment compared to placebo as assessed by the GSDS. CONCLUSIONS: Although we found a statistically significant improvement in actigraphically measured total sleep time on 50 mg melatonin compared to 5 mg or placebo, this small improvement (10 min) may not be clinically significant. However, the significant improvement found in subjective sleep disturbance suggests that these modest effects may be clinically relevant in this patient population.     

Tef polymorphism is associated with sleep disturbances in patients with Parkinson's disease

ObjectiveCircadian mechanisms play an important role in the regulation of sleep. A circadian clock-controlled gene, Tef, has been suggested to be associated with depressive symptoms, restless legs syndrome, and slow wave sleep in patients with sleep disorders. The present study sought to explore the association between Tef and sleep disturbances in patients with Parkinson’s disease (PD).MethodsThree hundred and ninety-two unrelated patients with PD were recruited for this study. All of them completed the PD Sleep Scale (PDSS) and other clinical and demographic assessments. rs738499, a single nucleotide polymorphism of the Tef gene, was genotyped by polymerase chain reaction-restriction fragment length polymorphism.ResultsMean total PDSS scores were 111.5 (standard deviation [SD] 23.0) in the TT genotype and 122.2 (SD 18.2) in the TG+GG genotypes (P < 0.01). Significant differences were found between genotypes (TT vs TG+GG) for 14 item scores (all P < 0.05). Total and item scores displayed negative associations with the TT genotype (all P < 0.05) except Item 2 (P = 0.178). Linear regression adjusted for gender, duration, depression and disease severity showed that the polymorphism could explain 0.9% of the variance in PDSS scores.ConclusionsThese preliminary results suggest that the TT genotype in Tef rs738499 is associated with sleep disturbances in PD. Depression and disease severity are the main contributors to these findings, but rs738499 itself is an independent risk factor.     

A review of normal sleep and its disturbances in Parkinson's disease

Patients with Parkinson's disease frequently report sleep disturbances which include difficulty initiating or maintaining sleep, parasomnias or excessive daytime sleepiness. The underlying causes include: normal aging, motor symptoms of the disease, antiparkinson drugs, comorbid psychiatric conditions, and concurrent illnesses. An accurate history from the patient and care-giver regarding previous sleep patterns and how they have changed, and the degree of impact these sleep disturbances have on patient's daily life is crucial for successful management. Apart from drug therapy, appropriate counselling and nonpharmacologic treatments have major roles in the overall management. This review summarizes the current concepts of (i) the pattern and function of normal sleep, and (ii) the nature, pathogenesis and management of sleep disturbances in Parkinson's disease.     

Nocturnal sleep disturbances and daytime dysfunction in patients with Parkinson's disease and in their caregivers

BACKGROUND: The role of aging, disease, medications, and mood disturbances in sleep disturbances (SD) in patients with Parkinson's disease (PD) is poorly understood, and the impact of SD on the quality of life of their caregivers (CG) largely undocumented. OBJECTIVES: To evaluate the pattern and determinants of disturbed sleep in PD patients complaining of SD, and in their primary CG. METHODS: A prospective evaluation of 40 non-demented patients with PD complaining of SD and 23 of their primary CG (all were spouses) was conducted using Pittsburgh Sleep Quality Index, Zung's self-rating depression and anxiety scales, Parkinson's Impact Scale (PIMS) (only for PD), and an additional sleep questionnaire. RESULTS: Eighty-four percent of patients were 'poor sleepers' with global sleep scores (GLSc) > 5. Other abnormalities were: excessive daytime sleepiness-57.5%, excessive daytime fatigue-72.5%, depression-51.5%, anxiety-63.1%, and abnormal PIMS score-83.8%. There was no correlation between the degree of sleep dysfunction and the age, severity, duration of PD or its treatment. Several component sleep scores correlated with anxiety scores, PIMS score with depression, and, subjects with GLSc > or = 10 had higher mean anxiety index. Daytime dysfunction (97.5%) was mainly associated with reduced enthusiasm, rather than excessive sleepiness. Among CG, 40% had a GLSc > 5, 21% had depression, and 10.5% had anxiety. Their depression, anxiety and sleep scores correlated with those of their spouses. CONCLUSIONS: PD patients with significant SD may represent a subset of patients with early, progressive degeneration of sleep centres, rather than an enhanced aging process. They are more susceptible mood disturbances, which correlate with the severity of sleep dysfunction. Sleep and mood disturbances also adversely affect the quality of life of spousal caregivers.     

Range of neuropsychiatric disturbances in patients with Parkinson's disease

OBJECTIVES: Disturbances of cognition and emotion are common in patients with Parkinson's disease. Most previous studies of psychopathology in Parkinson's disease have focused on a single psychiatric diagnosis or condition. The objective of this study was to describe the range of neuropsychiatric symptoms in a representative sample of patients with Parkinson's disease. METHODS: The sample of 139 patients was drawn from an epidemiological study of Parkinson's disease in Rogaland county, Norway, and represented 93% of those who had survived during the 4 years since the initial assessment. The diagnosis of Parkinson's disease was based on published criteria. Neuropsychiatric symptoms were assessed using the neuropsychiatric inventory, a caregiver based structured interview, which assesses severity and frequency of 10 psychiatric symptoms present during the past month. RESULTS: At least one psychiatric symptom was reported in 61% of the sample. The most common behaviours were depression (38%) and hallucinations (27%), and the least common symptoms were euphoria and disinhibition. The highest mean scores were found for depression, apathy, and hallucinations. Factor analysis showed that hallucinations, delusions, and irritability clustered into one factor, and apathy and anxiety constituted another factor. Psychiatric symptoms were more common among patients living in nursing homes compared with home dwelling patients, and correlated with stage of disease and cognitive impairment, but not with age or duration of disease. No relation to left or right sided parkinsonism was found. CONCLUSION: This study emphasises the importance of psychiatric symptoms in Parkinson's disease, which were present in most patients. Clinicians should focus on the emotional and cognitive disturbances in addition to the motor manifestations of the disease.     

Autonomic nervous system disturbances in Parkinson's disease]

On the basis of neurophysiological tests we conclude that subclinical signs of dysautonomia appear in Parkinsonians. Various autonomic functions are not disturbed in the same degree. Examinations of cardiovascular system showed that functions connected with parasympathetic system were affected, while those connected with sympathetic part were not. Examinations of skin sympathetic reflexes displayed rather patchy, disseminated type of damage: only latencies of responses recorded from hands (but not from feet) were prolonged when compared to the control group.     

Differences in sleep in patients with Parkinson's disease.

Twenty-three Parkinson patients were recorded during 2 or 3 consecutive nights. Their treatment, if any, was withdrawn for at least 15 days before the first recording session. Some qualitative abnormalities were noticed during each night in 13 of these patients. They consisted in: 1. Repetitive blinking at the beginning of the night when the lights were turned off, persistence of the electromyographic activity of the chin muscles during paradoxical sleep, occurrence of rapid eye movements and blepharospasms during slow wave sleep before the onset of paradoxical sleep episodes, and alpha rhythm during paradoxical sleep. 2. The study of these signs showed that association between blinking and persistence of the activity of the chin muscles during paradoxical sleep is never encountered. 3. The patients with chin muscle activity during paradoxical sleep had a 50% decrease in paradoxical sleep as compared with the group of patients with repetitive blinking. 4. The possibility that lesions of the locus coeruleus are responsible for this decrease in paradoxical sleep is discussed.     

Sleep disturbances in Parkinson's disease with emphasis on rapid eye movement sleep behavior disorder

Sleep disturbances are common in patients with Parkinson's disease (PD). These disturbances can primarily affect the patient's quality of life and may worsen the symptoms of PD. Among the multiple sleep disturbances in PD patients, there has been a marked growing interest in rapid eye movement (REM) sleep behavior disorder (RBD). This is likely due to the fact that RBD has been proven to precede the motor symptoms of PD by many years. The aim of this article is to examine the sleep disturbances found in PD, with special attention to RBD as a premotor symptom of PD, as well as to assess its proposed related pathophysiology. MEDLINE (1966-March 2010), American Academy of Sleep Medicine's, The International Classification of Sleep Disorders, and current textbooks of sleep medicine were searched for relevant information. Search terms: RBD, sleep disturbances, Parkinson's disease, and pre-motor were used. Excessive daytime sleepiness (EDS), sleep attack, insomnia, restless leg syndrome (RLS), sleep-disordered breathing (SDB), and RBD are sleep disturbances commonly found in the literature related to PD. Sleep benefit has been proven to lessen PD motor symptoms. RBD has been described as a premotor symptom of PD in several prospective, retrospective, and cross-sectional studies. Sleep disturbances in PD can result secondarily to natural disease progression, as a side effect of the medications used in PD, or in result of pre-clinical pathology. Treatment of sleep disturbances in PD patients is crucial, as what is termed as, "sleep benefit effect" has been shown to improve the symptoms of PD.     

Olfactory deficits and sleep disturbances in Parkinson's disease: a case-control survey

BACKGROUND: Olfactory and sleep disturbances are common in Parkinson's disease, and may be early disease indicators. OBJECTIVE: To obtain information about olfactory and sleep deficits preceding the onset of motor symptoms in Parkinson's disease. SUBJECTS: 38 community dwelling patients with Parkinson's disease (73% response rate) and 32 age matched controls (60% response rate). METHODS: Using a questionnaire survey, the frequencies, timing, and relations between olfactory and sleep disturbances, drug treatment, mood, and motor deficits in Parkinson's disease were compared with those in age matched controls. Reliability of information was validated by informant interview in 9% of the sample. Interdependency of factors was assessed using Fisher's fourfold table test, and differences between populations were analysed using chi(2) and unpaired t tests. RESULTS: Microsmia was reported by 26 patients (68%) (and only one control), on average within a year of the diagnosis of Parkinson's disease. More patients than controls had excessive daytime somnolence (45% v 6%), restless legs (50% v 19%), and abnormal movements during sleep (34% v 0%), which generally occurred three to five years after diagnosis and were independent of mood disorders and drug treatment. CONCLUSIONS: Many patients with Parkinson's disease have microsmia at the onset of motor deficits, but some sleep disorders are a subsequent occurrence.     

Sleep disturbances in Parkinson's disease

Parkinson's disease is a progressive disorder of the central nervous system. Degeneration of the dopaminergic neurons is the main cause of the disease. The basic symptoms of Parkinson's disease are bradykinesia, rigidity and resting tremor. Disturbances of the autonomous nervous system, depression, dementia and sleep disorders are common, too. People with Parkinson's disease suffer from insomnia, excessive daytime sleepiness, "sleep attacks", nightmares, REM sleep behaviour disorder, periodic limb movement in sleep, restless legs syndrome and sleep apnea syndrome. The main cause of sleep disorders in Parkinson's disease are age-connected changes in sleep architecture, disturbances of neurotransmission, movement disturbances in sleep, medications and concomitant diseases. The authors present the current state of knowledge on sleep disorders in Parkinson's disease, especially, the role of dopaminergic therapy, methods of diagnostics and treatment as well as the influence of sleep disturbances on patient's quality of life.     

Polysomnographic sleep measures in Parkinson's disease patients with treatment-induced hallucinations

Prior studies of sleep in Parkinson's disease (PD) have been compromised by inadequate comparison groups, mixed medication regimens, and absence of quantitative data collection. This is the first study to compare polysomnographic sleep measures in PD patients on only dopaminergic medications with and without hallucinations. We performed two consecutive nights of polysomnography in 10 nondepresed, nondemented PD patients, 5 with and 5 without hallucinations. All patients were being treated with carbidopa/levodopa and a dopaminergic agonist only. Hallucinators and nonhallucinators were group-matched for age, PD duration, severity, and medication doses. Both groups had abnormal sleep records. In particular, there was a reduction in K-complexes and spindle formation, and the frequent occurrence of motor activation during rapid eye movement (REM) sleep consistent with REM behavior disorder. The hallucinator group had a significantly lower sleep efficiency (0.25 in hallucinators vs 0.61 in nonhallucinators, p = 0.006), a reduced total REM sleep time (mean total REM sleep time, 3 minutes in hallucinators vs 50 in nonhallucinators; p = 0.005), and a reduced REM percentage (mean, 5% in hallucinators vs 20% in nonhallucinators; p = 0.011). This study demonstrates that advanced PD patients treated with dopaminergic agents have abnormal sleep patterns and that those with dopaminergic-induced hallucinations have significantly greater REM aberrations than nonhallucinating PD patients.     

Nonmotor disturbances in Parkinson's disease

Nonmotor disturbances (NMDs) affect most patients with Parkinson's disease (PD) and often have a profound impact on their quality of life. NMDs such as depression, anxiety, fatigue, REM sleep behavior disorder, constipation, delayed gastric emptying, altered olfaction and pain can precede the onset of motor symptoms. Other NMDs, including hallucinations, dementia, excessive daytime sleepiness, insomnia, orthostatic hypotension and bladder disturbances, typically appear later in the course of PD. For most NMDs of PD, nondopaminergic and non-nigrostriatal mechanisms (e.g. neurodegeneration of other transmitter systems in the cortex and brainstem, side effects of medications, genetic and psychosocial factors) are considered more relevant than the 'classical' dopaminergic-nigrostriatal dysfunction. The recognition of NMDs requires a high degree of clinical suspicion, the use of specific questionnaires and ancillary tests. Pharmacological and nonpharmacological approaches can be effective, but for most forms of treatment of NMDs, the scientific evidence is limited.     

Cognitive disturbances in Parkinson's disease

To test the hypothesis that the cognitive impairments that accompany Parkinson's disease (PD) arise from frontal lobe dysfunction, patients with idiopathic PD and controls were tested on a neuropsychological battery that included measures of anterograde memory, visuospatial perception, and naming, as well as several tests that are known to be sensitive to lesions of the frontal lobes. PD patients of normal mental status as measured by the Mini-Mental State Examination performed normally on the naming, line orientation, and verbal recognition memory tests but exhibited deficits on verbal recall. On tests of frontal lobe function, these patients showed mild deficits on a category fluency task and on the Wisconsin Card Sorting Test. However, their errors on the latter were not typical of patients with frontal lesions, and they performed normally on a letter fluency task and exhibited normal release from proactive interference. Patients of lower than normal mental status performed poorly on nearly all of the cognitive tasks including confrontational naming, line orientation, and recognition memory, suggesting that their cerebral dysfunction extended beyond subcortical-frontal circuits. The present study supports the usefulness of the Mini-Mental State Examination for cognitive screening of PD patients, but does not support the hypothesis that the cognitive impairments in PD arise principally from disruption of frontal lobe functioning.     

Behavioral disturbances in Parkinson's disease

Treatment of Parkinson's disease (PD) is complex and often involves addressing behavioral changes in addition to the movement disorder. Patients with PD are susceptible to any psychiatric condition seen in the general population; some disorders, such as depression and anxiety, may result from PD-related neuropathological changes. Medicationrelated hallucinations are seen in many PD patients who are treated with dopaminergic agents for motor symptoms. Cognitive impairment is also seen and can be multifactorial. Treatment of behavioral symptoms in PD can greatly improve patients" overall function and quality of life. As surgical interventions to treat motor symptoms, such as deep brain stimulation of the subthalamic nucleus of the substantia nigra, become more prevalent, the behavioral effects of these procedures must also be addressed.     

帕金森病患者睡眠障碍的临床分析

目的探讨帕金森病(PD)患者睡眠障碍的临床特征、睡眠质量评价,并分析其相关影响因素。方法采用匹兹堡睡眠质量指数量表(PSQI)、爱泼沃斯嗜睡量表(ESS)、简明精神状态量表(MMSE)、UPDRS-Ⅲ分量表、Hoehn-Yahr(H-Y)分级、综合医院焦虑/抑郁情绪测定表(HAD)及自制的睡眠情况及用药调查表分别对170例PD患者的睡眠状况、疾病严重程度、认知状况、抑郁程度、病程、多巴胺能药物应用等情况进行评定和计算。结果在170例PD患者中有141例睡眠质量差,发生率为82.9%。其中入睡困难102例(60.0%),睡眠破碎96例(56.5%),白天过度嗜睡59例(34.7%),睡眠运动障碍81例(47.7%)。多因素逐步线性回归分析显示PSQI总分与UPDRS-Ⅲ评分、H-Y分级、HAD评分、MMSE评分、左旋多巴日平均剂量及年龄相关,而与性别和病程长短无关;ESS仅与UPDRS-Ⅲ评分、左旋多巴日平均剂量相关。结论PD患者总体睡眠质量差,睡眠障碍的发生率高,主要表现为入睡困难、睡眠破碎、睡眠运动障碍、白天过度嗜睡等。PD患者睡眠障碍状况受病情严重程度、认知状态、抑郁、年龄、多巴胺能药物应用等因素影响,而与性别、PD病程长短无关。     

帕金森病患者客观睡眠障碍的特点

目的 研究帕金森病(PD)患者客观睡眠障碍的特点及相关因素.方法 收集患者病史资料,对101例PD患者(PD组)和90名年龄、性别相匹配的健康体检者(对照组)进行多导睡眠图监测,分析睡眠参数及其相关因素.结果 PD组与对照组比较:睡眠潜伏期差异无统计学意义:非快速眼运动睡眠1期比例(％)显著增多(27.9±17.8与21.2±11.7,t=3.034,P=0.003),非快速眼运动睡眠2期比例(％)显著减少(47.8±17.4与54.7±12.9,t=-3.043,P=0.003);睡眠效率下降,慢波睡眠比例、快速眼运动睡眠比例减少,觉醒次数增多,快速眼运动睡眠潜伏期延长,但差异均无统计学意义.PD患者部分睡眠参数与增龄、疾病严重程度、抑郁程度相关.40.6％ (41/101)PD患者睡眠期周期性肢体运动指数( PLMSI)大于15,而未主诉相关症状;PD组PLMSI显著高于对照组,且随年龄增大,PLMSI增高(r=0.261,P＜0.01).PD组呼吸暂停低通气指数、氧减指数较对照组无显著降低,最低血氧饱和度显著高于对照组.82.2％( 83/101) PD患者出现快速眼运动睡眠期肌张力失弛缓现象,其中38例(37.6％)诊断为快速眼运动睡眠期行为障碍;PD组快速眼运动睡眠期行为障碍、肌张力失弛缓的发生率均较对照组[0和8例(8.9％)]明显增高(x2=42.271、102.480,均P＜0.01).结论 PD患者睡眠结构等多项睡眠参数发生改变,其入睡困难不明显,以睡眠维持困难、睡眠结构紊乱为主,睡眠参数与增龄、疾病严重程度、抑郁程度相关;无症状的周期性肢体运动发生率高,不需特殊处理;患者可发生呼吸暂停或低通气,但血氧饱和度降低不严重,快速眼运动睡眠期行为障碍发生率高.