伴有快动眼睡眠行为障碍帕金森患者的震颤特征及多巴反应性

目的研究伴与不伴快动眼睡眠行为障碍(rapid eye movement sleep behavior disorder,RBD)的帕金森病(Parkinson disease,PD)患者的震颤特征及多巴反应性。方法根据2014年国际睡眠障碍分类第三版RBD的临床最低诊断标准,本研究采用RBD筛查问卷(RBD screening questionnaire,RBDSQ)量表来诊断临床很可能RBD(clinically probable RBD,cpRBD),将PD患者分为伴有cpRBD的PD(PD+cpRBD)与不伴有cpRBD的PD(PD-cpRBD)两组。对入组患者进行一般资料的收集,采用修订的H-Y分级、统一帕金森评分量表3.0版运动检查部分(UPDRS-Ⅲ)、MDS-UPDRS震颤量表对患者的运动功能进行评估,并且分别对两组患者首发侧肢体姿势性震颤、动作性震颤及静止性震颤的幅度进行评分,比较两组患者一般资料及震颤特征的差异性。对所有患者行急性左旋多巴冲击试验,将两组患者UPDRS-Ⅲ及MDS-UPDRS震颤量表评分最大改善率进行比较。结果共纳入42例伴有震颤的PD患者,PD+cpRBD组19例,PD-cpRBD组共23例,两组患者在性别、年龄、发病年龄、病程、关期UPDRS-Ⅲ评分及H-Y分级方面均无明显差异(P0.05)。与PD-cpRBD组相比,PD+cpRBD组关期震颤评分明显增高(t=2.379,P=0.022),震颤症状由首发侧肢体进展至对侧肢体的时间短(u=-2.133,P=0.033),首发侧肢体静止性震颤幅度大(u=-2.956,P=0.003),动作性震颤幅度大(u=-2.657,P=0.008)。口服左旋多巴/苄丝肼(200/50 mg)后,PD-cpRBD组的UPDRS-Ⅲ及震颤评分最大改善率均明显高于PD+cpRBD组(UPDRS-Ⅲ最大改善率u=-3.134,P=0.002;震颤评分最大改善率t=-3.189,P=0.003)。结论本研究表明,伴有cpRBD的PD患者震颤程度相对较重,以静止性震颤和动作性震颤为主,由首发侧肢体进展至对侧肢体的时间相对较短,对左旋多巴的反应性较差。     

Periodic limb movements in sleep and periodic limb movement disorder

Neurological Sciences - Previously referred to as “nocturnal myoclonus”, periodic limb movements in sleep (PLMS) is regarded as a distinct nosologic entity, although it overlaps a great...     

Clinical manifestations of Parkinson disease and the onset of rapid eye movement sleep behavior disorder

ObjectiveTo identify whether the presence and/or timing of rapid eye movement (REM) sleep behavior disorder (RBD) onset were associated with differences in clinical features and sleep parameters of Parkinson disease (PD).MethodsIn all, 112 PD patients were enrolled and all underwent extensive clinical evaluations and video-polysomnography (PSG). Clinical features and PSG parameters were compared in PD patients with (PD + RBD) or without (PD − RBD) RBD, RBD preceding (RBD > PD), or not (PD ⩾ RBD) PD onset.ResultsSixty-three of the 112 PD patients were affected by RBD. Adjusted for age, gender, education, body mass index (BMI), levodopa equivalent daily dose (LED) and PD duration, PD + RBD patients had higher Hoehn & Yahr stage, higher scores for UPDRS parts I, II and III, more dyskinesia, higher ratio of axial/limb manifestations, and more hallucinations. Their cognitive and quality-of-life status was significantly lower (all P < 0.05). For PSG, PD + RBD patients exhibited higher percentages of phasic and tonic EMG activities, lower apnea hypopnea (AHI) and oxygen desaturation index (ODI), and less time in arterial oxygen saturation (SaO₂) <90% during REM sleep (all P < 0.05). PD ⩾ RBD (n = 22) patients did not significantly differ from RBD > PD (n = 41) patients in clinical manifestations, whereas the PD ⩾ RBD subgroup had significantly higher UPDRS part I score, lower PDQ score and lower AHI during REM than the PD − RBD group (all P < 0.05), but not RBD > PD subgroup. Correlation analysis showed that worse cognition was associated with shorter interval of RBD preceding PD onset (r = 0.297, P = 0.018), but not RBD duration (P = 0.202).ConclusionsClinical manifestations of PD may vary depending on the presence and timing of RBD onset. These findings are compatible with the hypothesis that RBD may be a marker of complex subtypes of PD.     

Rapid eye movement sleep behavior disorder in treatment-naïve Parkinson disease patients

Objective

Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for dementia in Parkinson disease (PD) patients. The objectives of our study were to prospectively evaluate the frequency of RBD in a sample of treatment-naïve, newly diagnosed PD patients and compare sleep characteristics and cognition in RBD and non-RBD groups.

Methods

Fifty-seven newly diagnosed PD patients were consecutively recruited in a university medical center. All patients underwent two overnight polysomnography (PSG) sessions and were diagnosed with RBD according to the International Classification of Sleep Disorders, Second Revision criteria. Daytime sleepiness was measured in a multiple sleep latency test (MSLT). Cognition was assessed in a standard neuropsychologic examination.

Results

Seventeen PD patients (30%) met the criteria for RBD. The RBD patients and non-RBD patients did not significantly differ in mean age, gender ratio, disease duration, motor symptom subtype and severity, total sleep time, percentage of REM sleep, apnea–hypopnea index, mean oxygen saturation, and importantly cognitive performance. However, non-RBD patients had a significantly shorter mean daytime sleep latency than RBD patients (15 vs 18 min, respectively; P = .014).

Conclusion

A high frequency of RBD was found in our sample of 57 newly diagnosed PD patients. At this stage in the disease, RBD was not found to be associated with other sleep disorders or cognitive decline. Follow-up is needed to assess the risk for developing dementia in early-stage PD patients with RBD.     

Perspectives on the rapid eye movement sleep switch in rapid eye movement sleep behavior disorder

Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus (SLD) of the dorsal pons are critical for generation for REM sleep atonia. Descending projections from SLD glutamatergic neurons activate inhibitory premotor neurons in the ventromedial medulla (VMM) and in the spinal cord to antagonize the glutamatergic supraspinal inputs on the motor neurons during REM sleep. REM sleep behavior disorder (RBD) consists of simple behaviors (i.e., twitching, jerking) and complex behaviors (i.e., defensive behavior, talking). Animal research has lead to the hypothesis that complex behaviors in RBD are due to SLD pathology, while simple behaviors of RBD may be due to less severe SLD pathology or dysfunction of the VMM, ventral pons, or spinal cord.     

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.     

Bupropion SR reduces periodic limb movements associated with arousals from sleep in depressed patients with periodic limb movement disorder

BACKGROUND: Antidepressant-induced periodic limb movement disorder (PLMD) may limit the tolerability of some antidepressant medications and interfere with treatment response. Given the role of dopamine in PLMD and the effects of bupropion sustained-release (SR) on central dopaminergic function, we hypothesized that bupropion SR would not be associated with antidepressant-induced PLMD. METHOD: In an expanded case-series design, we compared the effects of bupropion SR, after about 10 weeks of treatment, on measures of PLMD, depression, and sleep in 5 depressed (Research Diagnostic Criteria) patients who also met criteria for having pretreatment PLMD. Depression was measured using the Beck Depression Inventory and the Hamilton Rating Scale for Depression. Patients were considered to have PLMD if polysomnographic recordings showed > 5 periodic limb movements/hour of sleep that were associated with arousals from sleep. RESULTS: Bupropion SR treatment was associated with a reduction in measures of PLMD and an improvement in depression. CONCLUSION: These results show that bupropion SR is not associated with antidepressant-induced PLMD. Rather, bupropion SR treatment reduces objective measures of PLMD in depressed patients with the disorder.     

Impulse control disorder and rapid eye movement sleep behavior disorder in Parkinson's disease

IntroductionThe relationship between ICD and RBD is still not yet understood and the results from the current literature are contradictory in PD. We aimed to explore the association between rapid eye movement (REM) sleep behavior disorder (RBD) and impulse control disorder in Parkinson's disease.MethodsNinety-eight non-demented patients with Parkinson's disease underwent one night of video-polysomnography recording. The diagnosis of RBD was established according to clinical and polysomnographic criteria. Impulse control disorders were determined by a gold standard, semi-structured diagnostic interview.ResultsHalf of the patients (n = 49) reported clinical history of RBD while polysomnographic diagnosis of RBD was confirmed in 31.6% of the patients (n = 31). At least one impulse control disorder was identified in 21.4% of patients, 22.6% with RBD and 20.9% without. Logistic regression controlling for potential confounders indicated that both clinical RBD (OR = 0.34, 95% CI = 0.07–1.48, P = 0.15) and polysomnographic confirmed RBD diagnoses (OR = 0.1.28, 95% CI = 0.31–5.33, P = 0.34) were not associated with impulse control disorder.ConclusionIn Parkinson's disease, REM Sleep Behavior Disorder is not associated with impulse control disorder. The results of our study do not support the notion that PSG-confirmed RBD and ICD share a common pathophysiology.     

Morbidities in rapid eye movement sleep behavior disorder

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, RBD without any obvious comorbid major neurological disease), is strongly associated with numerous comorbid conditions. The most prominent is that with neurodegenerative disorders, especially synuclein-mediated disorders, above all Parkinson disease (PD). Idiopathic RBD is an important risk factor for the development of synucleinopathies. Comorbidity studies suggest that iRBD is associated with a number of other potential pre-motor manifestations of synucleinopathies such as, cognitive and olfactory impairment, reduced autonomic function, neuropsychiatric manifestations and sleep complaints. Furthermore, patients with PD and RBD may have worse prognosis in terms of impaired cognitive function and overall morbidity/mortality; in dementia, the presence of RBD is strongly associated with clinical hallmarks and pathological findings of dementia with Lewy bodies. These findings underline the progressive disease process, suggesting involvement of more brain regions in patients with a more advanced disease stage. RBD is also associated with narcolepsy, and it is likely that RBD associated with narcolepsy is a distinct subtype associated with different comorbidities. RBD is also associated with antidepressant medications, autoimmune conditions, and, in rare cases, brainstem lesions.     

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。     

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.     

Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinson's disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty‐six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self‐report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future. © 2014 International Parkinson and Movement Disorder Society     

Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy

Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic motor activities in REM sleep and dream-enacting behavior are mostly reported in presence of cataplexy. Narcolepsy without cataplexy is a condition rarely associated with hypocretin deficiency. We proposed that hypocretin neurons are centrally involved in motor control during wakefulness and sleep in humans, and that hypocretin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakefulness and RBD/RSWA/phasic motor activity during REM sleep.     

Neural substrates of rapid eye movement sleep behavior disorder in Parkinson's disease

ObjectivesTo investigate neural substrates of symptomatic rapid eye movement sleep behavior disorder (RBD) in Parkinson's disease (PD) by analyzing brain changes based on both hypothesis-free and hypothesis-driven neuroimaging analyses.MethodsA total of 63 subjects (14 PDRBD−, 24 PDRBD+, and 25 age-matched healthy controls = HC) were enrolled in this study. RBD was defined by RBD screening questionnaire with video-polysomnographic confirmation. All subjects underwent volumetric and diffusion tensor imaging. The whole brain gray- and white-matter changes were analyzed and the central ascending cholinergic pathway involving the pedunculopontine nucleus and thalamus was compared with a region-of-interest analysis and probabilistic tractography.ResultsThe PDRBD+ group showed decreased gray matter volume of the left posterior cingulate and hippocampus compared to the PDRBD− and additional gray matter decrease in the left precuneus, cuneus, medial frontal gyrus, postcentral gyrus and both inferior parietal lobule compared to the HC group (uncorrected p < 0.001, k = 50). There were no significant differences in white matter changes between the PDRBD− and PDRBD+ groups both by fractional anisotropy and mean diffusivities. However, both PD groups showed widespread changes by fractional anisotropy reductions and mean diffusivity increments compared to HC (p < 0.05 corrected). There were no significant differences in tract-based spatial statistics and the normalized tract volumes as well as the diffusion indices of both the thalamus and pedunculopontine nuclei among the study groups.ConclusionsThe appearance of RBD in PD may be related to regional gray matter changes in the left posterior cingulate and hippocampus but not localized to the brainstem.     

特发性快速眼动睡眠期行为障碍经颅脑实质超声研究

目的探讨快速眼动睡眠期行为障碍患者经颅脑实质超声改变。方法符合睡眠障碍国际分类第2版快速眼动睡眠期行为障碍诊断标准的15例患者(RBD组)和15例正常对照受试者,于多导睡眠图监测后通过经颅脑实质超声检查并测量中脑黑质高回声、基底节高回声、第三脑室宽度;简易智能状态检查量表(MMSE)和蒙特利尔认知评价量表(MoCA)评价认知功能。结果快速眼动睡眠期行为障碍患者具有典型的临床表现和电生理学改变。RBD组黑质高回声(6/15)、基底节高回声(7/15)阳性检出率,与正常对照组(1/15和2/15)之间差异无统计学意义(P=0.080,0.109)。RBD组伴与不伴黑质高回声患者MoCA评分差异无统计学意义(P=0.075);但RBD组伴基底节高回声患者MMSE评分高于不伴基底节高回声患者(P=0.021)。结论快速眼动睡眠期行为障碍作为突触共核蛋白病前驱期,经颅脑实质超声可表现为黑质和基底节高回声,且伴不同结局。经颅脑实质超声可以检测出脑亚临床改变,评价突触共核蛋白病风险。     

Periodic leg movements during sleep and periodic limb movement disorder in patients presenting with unexplained insomnia

ObjectiveThe aim of this study was to evaluate quantitatively the presence and the characteristics of periodic leg movements during sleep (PLMS) in a group of consecutive patients presenting with daytime impairment related to insomnia of unknown etiology and whose polysomnographic features differ from those of healthy individuals only for a significantly increased arousal index in NREM sleep.MethodsWe recruited 20 consecutive adult patients with insomnia according to the ICSD-2 criteria, 20 patients with RLS, and 12 age-matched normal controls. The time structure of their polysomnographically recorded leg movements during sleep was analyzed by means of an approach particularly able to consider their periodicity.ResultsA subgroup of 12 patients with a relatively high number of periodic LM activity was detected with a statistically based approach using two indexes: total LM index and Periodicity index. This subgroup had high PLMS index, Periodicity index was also high and PLMS showed a progressive decrease during the night, being highest in the first hours of sleep. The characteristics of PLMS were identical within this insomnia subgroup and RLS patients.ConclusionsPLMS was a common finding in our patients with insomnia and a detailed analysis of their periodicity revealed that a subgroup of these patients had to be finally diagnosed with Periodic Limb Movement Disorder.SignificancePolysomnography with the subsequent analysis of PLMS periodicity is able to differentiate between insomnia patient subgroups.     

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.