帕金森病合并快速眼动睡眠行为障碍与认知功能相关性的研究进展

<正>帕金森病(PD)的主要临床特征为静止性震颤、肌强直、运动迟缓及姿势步态异常,除了典型的运动症状外,PD患者还伴随众多非运动症状。认知功能障碍是PD不可忽略的非运动症状之一,PD早期即可出现认知功能受损[1]。近年来的研究显示,快速眼动睡眠行为障碍(RBD)可能是PD患者认知功能障碍的又一危险因素,为认知功能障碍提供早期识别和干预的机会,进而延缓PD痴呆(PD with dementia,PDD)     

帕金森病合并快速眼动睡眠行为障碍与认知损害相关性的研究进展

快速眼动睡眠行为障碍(rapid eye movement sleep behavior disorder,RBD)和认知损害(cognitive impairment,CI)都是帕金森病(Parkinson’s disease,PD)常见的非运动症状,大量研究表明,合并RBD的PD患者更易出现CI,且认知功能下降速度更快、认知损害程度更严重,明显降低PD患者生活质量、增加照料者负担。既往研究着重于RBD和帕金森病认知损害(Parkinson’s disease-cognitive impairment,PD-CI)的临床特征,本文进一步对伴RBD的PD患者在认知功能损害的领域以及RBD和PD-CI发生的病理基础及遗传学基础进行阐述,以便深入了解RBD与PD患者发生CI的关系。     

帕金森病合并快速眼动睡眠行为障碍与认知损害相关性的研究进展

快速眼动睡眠行为障碍（rapid eye movement sleep behavior disorder,RBD）和认知损害（cognitive impairment,CI）都是帕金森病（Parkinson's disease,PD）常见的非运动症状,大量研究表明,合并RBD的PD患者更易出现CI,且认知功能下降速度更快、认知损害程度更严重,明显降低PD患者生活质量、增加照料者负担。既往研究着重于RBD和帕金森病认知损害（Parkinson's disease-cognitive impairment,PD-CI）的临床特征,本文进一步对伴RBD的PD患者在认知功能损害的领域以及RBD和PD-CI发生的病理基础及遗传学基础进行阐述,以便深入了解RBD与PD患者发生CI的关系。     

帕金森病与快动眼睡眠行为障碍

快动眼期睡眠行为障碍(RBD)是以REM期睡眠肌肉失张力的消失、伴随梦境发生的暴力行为等为特点,患者常会伤及他人和自身。RBD与帕金森病(PD)密切相关,伴有RBD的PD与不伴有RBD的PD有着不同的发病模式。在少动-强直型PD患者,RBD可在PD典型症状出现之前发生。RBD在经颅脑超声信号、脑电图、脑血流灌注、多巴胺代谢等方面的异常表现越来越支持RBD可能是PD发病的一个阶段。多数患者对氯硝西泮治疗有效。     

帕金森病合并快速眼球运动睡眠行为障碍患者的客观睡眠结构及认知功能

目的 评价帕金森病合并快速眼球运动睡眠行为障碍(RBD)患者的睡眠结构及认知功能,并探讨其睡眠结构与认知功能之间的相关性.方法 本研究为横断面研究,以在我院睡眠中心进行睡眠监测的39例帕金森病合并RBD患者作为病例组,并以年龄、性别相匹配的21例原发性快速眼球运动睡眠行为障碍(iRBD)患者及37例不合并RBD的帕金森病患者作为对照组.所有患者均行整夜睡眠监测以定量睡眠相关参数,并且于监测当天使用蒙特利尔(MoCA)评估量表评估其认知功能.采用多重线性回归分析量表得分与睡眠结构之间的相关性.结果 (1)帕金森病合并RBD患者的睡眠效率(60.9％±16.9％)、总睡眠时间[(329.7±96.5)min]、非快速眼动睡眠2期时间[(127.6±67.6) min]及快速眼动睡眠期时间[(45.3 ±33.2) min]较iRBD组的相应值[77.8％±16.9％以及(397.1 ±88.9)、(188.0±94.7)、(70.6 ±25.9) min]比较明显减少(均P＜0.05),较不合并RBD的PD组的相应值[61.3％±21.7％以及(324.9 ±134.6)、(132.6 ±65.6)、(47.1±31.9)min]减少,但差异均无统计学意义.3组的睡眠潜伏期、快速眼球运动睡眠潜伏期、非快速眼球运动睡眠1期,慢波睡眠比例、氧减指数、呼吸暂停低通气指数及周期性肢体运动指数比较差异均无统计学意义.(2)帕金森病合并RBD患者认知功能最差,其中视空间与执行功能得分[(3.8±1.1)分]较iRBD组[(4.4±0.7)分]比较差异有统计学意义(F=3.426,P＜0.05).(3)多重线性回归显示帕金森病合并RBD患者的RBD病程、睡眠效率和非快速眼动睡眠2期与视空间与执行功能得分有相关性.结论 帕金森病合并RBD患者的睡眠效率、总睡眠、非快速眼动睡眠2期及快速眼动睡眠期时间和认知功能均明显下降,认知功能的改变与睡眠结构的变化可能存在相关性.     

特发性快动眼睡眠行为障碍与帕金森病研究进展

正快动眼睡眠行为障碍(RBD)是一种异态睡眠,主要表现为快动眼睡眠(REM)期异常的肌肉失弛缓(RSWA)及梦境演绎(如唱歌、喊叫、大笑、挥拳、打人、坠床等)。根据有无病因,分为特发性RBD(iRBD)和继发性RBD(sRBD)。目前,大量研究~([1])发现特发性RBD与神经变性病关系密切,其中约90%在确诊后的数年或十数年会发展为神经变性病,如路易体痴呆、帕金森病(PD)、多系统萎缩等。而PD作为老年人常见的神经变性病,严重影响着老年人的健康与生活质量,并且PD     

早期帕金森病患者快速眼动睡眠期行为障碍研究

目的探讨早期帕金森病患者快速眼动睡眠期行为障碍发生情况,以及帕金森病运动症状、非运动症状和快速眼动睡眠期行为障碍特点。方法共60例原发性帕金森病患者,采用统一帕金森病评价量表第二和第三部分(UPDRSⅡ和UPDRSⅢ)以及Hoehn-Yahr分期评价帕金森病非运动症状和运动症状,蒙特利尔认知评价量表评价认知功能,汉密尔顿焦虑量表和汉密尔顿抑郁量表评价焦虑和抑郁症状;中文版快速眼动睡眠期行为障碍筛查量表判断是否伴快速眼动睡眠期行为障碍,Epworth嗜睡量表(ESS)评价白天过度嗜睡程度;多导睡眠图监测睡眠障碍特征,包括下颌位相性肌电活动密度和快速眼动睡眠期肌肉失弛缓。结果 60例帕金森病患者中42例(70%)伴快速眼动睡眠期行为障碍(PD+RBD组),多导睡眠图监测其异常行为主要表现为上肢伸展抓握、肢体震颤抽搐、发笑、喊叫和怒骂等非暴力动作,仅2例出现暴力击打、蹬踢等异常行为。PD+RBD组患者年龄(P=0.024)、病程8年比例(P=0.000)、UPDRSⅡ(P=0.005)和UPDRSⅢ(P=0.001)评分、Hoehn-Yahr分期2级比例(P=0.007)、焦虑障碍(P=0.044)和抑郁障碍(P=0.001)比例,以及下颌位相性肌电活动密度(P=0.000)和快速眼动睡眠期肌肉失弛缓比例(P=0.000)均高于对照组,其中,PD+RBD组有16例(38.10%)快速眼动睡眠期行为障碍症状早于帕金森样症状5.20(3.91,6.51)年。结论年龄大、病程长、运动症状和非运动症状严重的帕金森病患者易伴发快速眼动睡眠期行为障碍,快速眼动睡眠期行为障碍可能是帕金森病的早期表现。多导睡眠图监测对早期帕金森病伴快速眼动睡眠期行为障碍的诊断有重要参考价值。     

阻塞性睡眠呼吸暂停及快动眼睡眠期行为障碍对帕金森病患者认知功能的影响

目的观察伴阻塞性睡眠呼吸暂停(OSA)及快动眼睡眠期行为障碍(RBD)对帕金森病(PD)患者认知功能的影响。方法收集101例PD患者的临床资料,采用MMSE、蒙特利尔认知评估量表(MoCA)北京版评定患者认知功能,并对患者进行整夜多导睡眠监测(PSG)并对相关结果进行比较。结果根据PSG监测结果,将患者分为对照组34例、OSA组18例、RBD组34例及OSA+RBD组15例。与对照组比较,RBD组及OSA+RBD组MoCA评分显著降低(均P0.05)。与OSA+RBD组比较,RBD组体质量指数及PD组Epworth嗜睡量表评分显著降低,RBD组慢波睡眠比例显著升高(均P0.05)。与OSA组及OSA+RBD组比较,对照组及RBD组呼吸暂停低通气指数及氧减指数显著降低,最低脉搏氧饱和度显著升高(均P0.05);OSA组的觉醒次数较其他三组显著升高(均P0.05)。在相关分析中,PD患者的MoCA评分与RBD(r=0.324,P=0.001)、总睡眠时间(r=0.212,P=0.035)、睡眠效率(r=0.272,P=0.006)、非快速眼动睡眠2期时间(r=0.257,P=0.010)呈正相关。结论认知功能障碍在伴RBD的PD患者中很常见。PD患者认知功能与睡眠效率、总睡眠时间、非快速眼动睡眠2期时间及RBD显著相关。     

帕金森病患者快速眼动睡眠行为障碍的临床特征

目的探讨帕金森病(PD)患者快速眼动睡眠行为障碍(RBD)的临床特征。方法连续收集2013年2月~2016年8月就诊于河北医科大学第一医院神经内科的61例PD患者,记录一般资料。对患者进行多导睡眠监测(PSG)和RBD筛查量表(RBDSQ)评估,根据结果将患者分为临床RBD组、亚临床RBD组和无RBD组。应用统一PD评定量表第三部分(UPDRSⅢ)、Hoehn-Yahr(H-Y)分级、汉密尔顿焦虑抑郁量表(HAMA14、HAMD24)、匹兹堡睡眠指数量表(PSQI)、MMSE、蒙特利尔认知评估量表(Mo CA)评估患者的运动及非运动症状,应用TCD检测患者黑质回声强度,对患者服用抗PD药物进行左旋多巴等效剂量(LDE)换算。结果最终入组56例患者,根据PSG和RBDSQ结果分为临床RBD组25例,亚临床RBD组22例,无RBD组9例。临床RBD组及亚临床RBD组病程明显短于无RBD组,两组患者所需的左旋多巴等效剂量(LDE)均多于无RBD组(均P0.05)。临床RBD组的H-Y分级和PSQI评分均显著高于亚临床RBD组及无RBD组,亚临床RBD组的H-Y分级和PSQI评分显著高于无RBD组(均P0.05)。临床RBD组TCD阳性检出率高于无RBD组(P0.05)。RBDSQ评分与病程呈负相关,与H-Y分级、LDE、PSQI评分呈正相关(均P0.05)。结论 PD患者RBD发生率高,伴RBD的患者病程短,RBD的严重程度与患者H-Y分级、LDE和总体睡眠质量显著相关。伴有临床RBD的PD患者黑质强回声的发生率高。     

帕金森病认知功能损害

帕金森病（Parkinson’s disease,PD）认知功能损害近年来受到人们的关注,PD认知损害严重影响患者的日常生活能力,早期诊断和干预PD认知损害将有助于延缓PD痴呆的发生。本文就PD认知功能损害的发生率、诊断标准及治疗等方面进行简要综述。     

Cognitive impairments in Parkinson's disease

Objective: Dementia and cognitive impairment (CI) are common in Parkinson's disease (PD) and have important clinical consequences. We explored the prognostic factors for CI in patients with PD.

Methods: A total of 102 patients with PD in Xuan wu hospital and Qian dongnan People's Hospital from 2005 to 2010 were included in this study. All patients underwent clinical and neurological assessments. Relevant demographic and performance parameters were analysed to determine variables that may be independently associated with the progression of CI.

Results: In the 6-month follow-up group, CI progressed in three out of 58 cases (5%): two cases progressed from mild CI (MiCI) to moderate CI (MoCI), and one case from MoCI to dementia. In the six-month-to-two-year follow-up group, seven out of 46 cases (15%) worsened: one case developed MiCI, three cases progressed from MiCI to MoCI and three other cases from MoCI to dementia. In the two-to-five-year group, 20 out of 44 cases (45%) worsened with one case developing MiCI, 14 cases progressing from MiCi to MoCI and five cases from MoCI to dementia. Compared with other patients, those with worsening of CI symptoms were significantly older in the two-to-five-year group. Progression of CI was also associated with age at onset and initial staging of PD.

Conclusions: Advanced age, late onset of disease and severity of PD are the predictive factors for the progression of CI in PD. The highest probability of progression of CI is in patients with initial severe impairments of visuospatial function.     

Cognitive impairments in Parkinson's disease.

The clinical neuropsychologic profiles of patients with Parkinson's disease and patients with SDAT show both overlap and dissociation. Speech, language, and certain memory skills are examples of dissociable differences, especially in the early stages of the disease. Furthermore the presence of depression, evidence of cognitive slowing, and absence of aphasia in patients with Parkinson's disease suggest prominent subcortical involvement. It is probably premature to categorize all of the cognitive changes in patients with Parkinson's disease as subcortical, however. Some skills, such as visuospatial and executive functions, are impaired in both disorders, and although the etiologic bases for task failure may differ for each, this issue remains open-ended. Another problem is that often the evidence for or against the cortical/subcortical distinction is insufficient and in some cases based on a single measure thought to be representative of a given cognitive domain. Most importantly there are few comparative studies that provide unequivocal support for making a cortical/subcortical distinction. Failure to equate for level of cognitive impairment or functional disability between dementias and strict adherence to cross-sectional study designs further compromise efforts to characterize each syndrome precisely. Whitehouse suggested that a prospective study of several different dementias studied in parallel, examining a wide range of cognitive skills, is required before the cortical/subcortical classification scheme can be validated. A critical component is an autopsy program to confirm diagnoses and provide clinicopathologic correlation. It is possible that the diverse nature of the cognitive impairment in patients with Parkinson's disease is not a methodologic artifact but reflects multiple disease subtypes. Ross, Mahler, and Cummings proposed three dementia syndromes in patients with Parkinson's disease: one that is relatively mild and meets the criteria for subcortical dementia, a second that is more severe and shows a wider range of cognitive impairment but is still neuropathologically distinct from SDAT, and a third severe dementia with both subcortical and cortical involvement that may reflect basal ganglia and Alzheimer-type pathology.     

Cognitive impairments associated with early Parkinson's disease

We administered a battery of cognitive tests to 41 recently diagnosed Parkinson patients and 41 controls to assess the early neuropsychological changes associated with Parkinson's disease (PD). Parkinson subjects did as well as controls on tasks assessing attention and select language and visuospatial measures. However, PD subjects did significantly worse on embedded figures, facial recognition, proverbs, and verbal and figural memory measures, and made more perseverative responses on a set shifting task. A discriminant function of measures of proverbs, embedded figures, and memory accounted for 22% of the variance between groups. These data suggest that the cognitive changes in early PD are more pervasive than originally described and may reflect the onset of a more widespread pathologic process.     

Cognitive impairments in different stages of Parkinson's disease

A consecutive series of 94 patients with Parkinson's disease (PD) were evaluated for the presence of depression and neuropsychological deficits. Patients were divided into groups based on the severity of their PD symptoms and then further subdivided into depressed and nondepressed groups. Both stage of PD and existence of depression had significant effects on neuropsychological performance. The nondepressed group with severe symptoms showed deficits in cognitive tasks involving motor speed, and the depressed patients with severe symptoms demonstrated impairments in frontal-lobe-related tasks.     

Cognitive impairments in Parkinson's disease: distinguishing between effort-demanding and automatic cognitive processes

The study was designed to define some of the elements of cognitive impairments evident in unmedicated Parkinson's disease (PD) patients. Unlike patients with progressive dementias such as Alzheimer's disease, untreated, mildly to moderately affected PD patients are efficient at accessing previously acquired knowledge. They also can learn and remember information that can be processed "automatically," using operations requiring little cognitive capacity. However, PD patients demonstrate relatively specific cognitive impairments for effort-demanding processes. These findings are clinically useful, but also help define the boundaries of psychobiologically distinct cognitive (memory-learning) processes.     

Cognitive impairments in Machado-Joseph disease

BACKGROUND: Cognitive function of Machado-Joseph disease (MJD) patients has not been clarified. OBJECTIVES: To determine the characteristics of cognitive dysfunction in MJD patients and to assess the relationship of dysfunction to age at onset, age at examination, disease duration, education, ataxia, depression, anxiety, and CAG repeat length. DESIGN: Case-control study. SETTING: Research-oriented hospitals. PARTICIPANTS: Sixteen genetically confirmed MJD patients able to complete neuropsychological tests and 20 control subjects matched to patients by age and education. MAIN OUTCOME MEASURES: Neuropsychological tests, including general cognition, verbal and visual memory, working memory, visuospatial and constructional ability, language, executive function, depression, and anxiety. RESULTS: Machado-Joseph disease patients scored significantly lower than controls in verbal and visual memory, in visuospatial and constructional tasks, and in phonemic and semantic fluency tasks. None of these impairments correlated with CAG repeat length, age at onset, age at examination, disease duration, or education. Verbal fluency (words named in a category) correlated with the International Cooperative Ataxia Rating Scale score. CONCLUSION: Machado-Joseph disease patients have verbal and visual memory deficits, visuospatial and constructional dysfunction, and verbal fluency deficits, all unrelated to CAG repeat length.     

Responsiveness of impairments and disabilities in Parkinson's disease

The objective of this study is to evaluate the responsiveness of items of the Activities of Daily Living (ADL) and Motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's Disease (PD). A standardized Response Mean (SRM) per item was calculated using data of four trials (n=376) that randomised patients with early PD to dopamine agonist (DA) monotherapy or placebo. In the ADL section, the SRMs ranged from -0.04 (no effect) to -0.50 (moderate effect). Hand functions were the most responsive ADL items with 'handwriting' showing the largest response. Self-assessed symptoms were the least responsive. In the Motor section, SRMs ranged from -0.09 to -0.60 with bradykinesia items showing the largest response, especially the item 'finger taps'. The tremor items showed the smallest response, however, rest tremor arms was much more responsive than rest tremor of the head and legs or postural tremor. SRMs in the placebo group ranged from 0.08 to -0.21 in the ADL section and from 0.03 to -0.35 in the Motor section. ADL and motor items have comparable and mostly small effect sizes. The most responsive items are in the ADL section hand functions and in the Motor section bradykinesia items. A more responsive ADL section would omit the self-assessed symptoms and the Motor section would retain only rest tremor arms of the tremor items.     

Cognitive dysfunction in non-demented Parkinson's disease patients: Controlled and automatic behavior

The evidence with regard to impaired automatic and controlled information processing in non-demented patients with Parkinson's disease (PD) is critically discussed. We use a comprehensive mental schema framework of executive functioning, that is the planning and regulation of behavior in complex everyday tasks (International Classification of Functioning - ICF - activity level).In this framework monitoring, inhibition, mental effort, planning, working memory and flexibility are important elements of controlled processing (supervisory attentional control) and controlled processing can only influence performance by modulating automatic processes. The striatum plays an important role in the interface between controlled and automatic processes.It is wel documented that PD patients show impairments applying and achieving automaticities. With sustained cortical control of task performance during both automatic and controlled processing, not showing the transition to striatal control, which is normal in the case of skill learning.In addition, PD patients have been shown to be limited in executive functioning. Many authors have interpreted this as evidence for impaired executive functions (ICF body level). But the question must be asked to what extent these limitations are an indirect effect of impaired automatic processing. To answer this question, studies on executive functioning are critically assessed with regard to the control they have provided for impaired automaticity.It is concluded that only for cognitive flexibility and working memory, the evidence for impairments is convincing because significant limitations have also been shown in tasks with very low automatic processing demands. Impairments in other executive functions, such as monitoring, inhibition and planning have not been convincingly shown in non-demented PD patients and are likely to be due to treatment strategies and factors such as fatigue.     

Selective impairments in implicit learning in Parkinson's disease

The basal ganglia are thought to participate in implicit sequence learning. However, the exact nature of this role has been difficult to determine in light of the conflicting evidence on implicit learning in subjects with Parkinson's disease (PD). We examined the performance of PD subjects using a modified form of the serial reaction time task, which ensured that learning remained implicit. Subjects with predominantly right-sided symptoms were trained on a 12-element sequence using the right hand. Although there was no evidence of sequence learning on the basis of response time savings, the subjects showed knowledge of the sequence when performance was assessed in terms of the number of errors made. This effect transferred to the left (untrained) hand as well. Thus, these data demonstrate that PD patients are not impaired at implicitly learning sequential order, but rather at the translation of sequence knowledge into rapid motor performance. Furthermore, the results suggest that the basal ganglia are not essential for implicit sequence learning in PD.