Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Sleep in Parkinson’s disease


Sleep disturbances are common in Parkinson’s disease and comprise the entire spectrum of sleep disorders. On the one hand regulation of sleep and wakefulness is affected in Parkinson’s disease, leading to the development of disorders, such as insomnia and daytime sleepiness. While on the other hand control of motor activity during sleep is impaired, with subsequent manifestation of parasomnias (mainly REM sleep behavior disorders, but also, albeit more rarely, sleepwalking, and overlap parasomnia). Restless legs syndrome has been reported to be frequent in patients with Parkinson’s disease, although there is no consensus on whether it is more frequent in Parkinson’s disease than in the general population. The same is true for sleep-related breathing disorders. Regarding the diagnosis of sleep disorders in patients with Parkinson’s disease, one of the main challenges is correctly identifying excessive daytime sleepiness as there are many potential confounding factors, for example it is necessary to distinguish sleep-related breathing disorders from medication effects, and to distinguish restless legs syndrome from the concomitant presence of potential mimics specific to Parkinson’s disease, such as akathisia, nocturnal leg cramps, nocturnal hypokinesia, early morning dystonia, etc. The correct diagnosis of REM sleep behavior disorder is also not always easy, and video-polysomnography should be performed in order to exclude mimic-like movements at the end of sleep apneas or violent periodic leg movements of sleep. These aspects and specific considerations about diagnosis and treatment of sleep disorders in patients with Parkinson’s disease will be reviewed.


Sleep and wakefulness regulation rely on a highly complex and integrated function of multiple brain areas and neurotransmitters, many of which have also been shown to be affected in patients with Parkinson disease (PD) [1,2,3,4,5,6,7]. With this pathophysiological background, it is not surprising that disturbances of sleep and wakefulness are almost ubiquitous in patients with PD. An oft-cited survey performed in 1988 found that among PD patients, 98% had experienced disabilities at night or on waking since the onset of their disease [8], and disturbed wakefulness regulation was shown to be a prominent feature in up to 30% of patients with PD [1, 2, 9,10,11].

Beyond the PD-related impairments of brain and neurotransmitter function there are other major contributing factors to disturbances of sleep and wakefulness in patients with PD, these include dopaminergic drugs, which are known to influence regulation of sleep and wakefulness, as well as other medications used in this elderly and often multimorbid population, co-morbidities, PD symptoms that impair patients' sleep, such as nocturnal akinesia, and genetic factors that predispose to certain disturbances of sleep and wakefulness [2, 9, 12,13,14]. Moreover, lifestyle factors and impulse control disorders, a frequent side effect of dopaminergic drugs, can also play a role in the development and continuation of sleep disturbances in patients with PD.

An interesting, yet often neglected feature of PD concerns the interaction of sleep and motor function, with sleep benefit, i.e. some patients experience an improvement of motor function upon awakening [15,16,17,18,19], while others experience positive effects of sleep deprivation on motor function [20,21,22].

In patients with PD, both the sleep macrostructure (manifesting for instance as sleep fragmentation and a relative increase in superficial sleep) [23, 24] and sleep microstructure, manifesting as disturbed integrity of certain sleep stages (e.g. disturbed sleep spindles and K-complexes, or insufficient muscle atonia during REM sleep) [25,26,27,28,29,30,31,32] are affected.

The range of sleep disturbances in PD comprises the full spectrum of sleep disorder categories as outlined in the International classification of sleep disorders 3rd edition (ICSD-3) [33]. The categories of sleep disturbances apparent in patients with PD thus comprise insomnia, disorders of daytime somnolence, sleep-related breathing disorders, circadian disorders, and sleep-related movement disorders, namely restless legs syndrome (RLS), and parasomnias. This heterogeneity of sleep phenotypes might reflect the well-known heterogeneity of PD motor phenotypes as well as the biologic (biomarker) heterogeneity of PD.

Insomnia and daytime sleepiness in patients with Parkinson’s disease

As outlined above, patients with PD frequently experience insomnia, most often as a disorder of sleep maintenance, but also as a disorder of sleep onset or early morning awakening. The diagnosis of insomnia is always based on subjective symptoms. Patients report difficulties falling asleep or maintaining sleep, early awakening or non-restorative sleep, associated with subjective concern or daytime impairment [1, 2, 9,10,11, 23]. Notably, there is sometimes a discrepancy between subjective complaints of insomnia and only subtle disturbances of sleep structure in otherwise healthy people, whereas in patients with PD, in addition to the subjective complaints of insomnia, there is often a significant manifest disruption of the integrity of sleep macro and microstructure.

Multiple studies have reported high prevalences of insomnia in patients with PD [10]. Gjerstad and co-workers investigated sleep in a prospective longitudinal cohort of 231 patients with PD, and performed an 8-year follow-up in 89 of them. The authors reported a large intraindividual variation in insomnia symptoms as evaluated by questionnaires, but found that in the population-averaged logistic regression model the presence of insomnia was related to female sex (p = 0.001, OR 2.21, 95% CI 1.36–3.59), disease duration (p = 0.009, OR 1.07, 95% CI 1.02–1.13) and to depression as measured by the Montgomery and Aasberg Depression Rating Scale (p = 0.03, OR 1.06, 95% CI 1.01–1.11) [34]. However, PD-specific treatment, namely dopaminergic drugs, can be responsible for these symptoms. Therefore, in another study the same group examined the frequency, development, and associated covariates for different types of insomnia complaints in a cohort of originally drug-naive patients with incident PD during the first 5 years of treatment after diagnosis of PD. Overall, in this study they found that the prevalence of insomnia did not increase at the 5-year follow-up in these early PD patients, but, after the initiation of dopaminergic medication, disorders of sleep maintenance significantly increased over time, whereas disorders of sleep onset decreased [35].

In a Dutch 5-year, longitudinal cohort study of 421 PD patients who were examined annually, Marinus and co-workers used a prospective cohort design to evaluate frequency, course, longitudinal associations, and risk factors of insomnia. Linear mixed models were used to identify factors associated with longitudinal changes in the SCOPA sleep scales. Presence of insomnia (defined as a nighttime sleep section of the SCOPA-SLEEP questionnaire score ≥7) was reported at baseline in 27% of the total of 412 PD patients evaluated, and insomnia symptoms developed at some point during the annual follow-up examinations in an additional 33% of patients who did not have insomnia at baseline (n = 302). Once again female sex was associated with higher SCOPA sleep disturbance scores as were depressive symptoms, more severe motor complications (dyskinesias and motor fluctuations), higher antiparkinsonian medication doses and sleep medication use. In addition there was an association with higher disability, higher autonomic dysfunction, presence of hallucinations, and postural instability gait difficulty phenotype [36].

Joy and co-workers evaluated newly diagnosed levodopa-naïve patients with PD and reported frequent and variable alteration of sleep macro-architecture in these patients [37]. However, Ferreira and co-workers reported poor sleep quality and sleep architecture changes in PD patients, which improved with levodopa following improvement of motor symptoms (reduction of rigidity and tremor), but dopamine did not reverse sleep architecture changes [38].

In a very large epidemiological dataset comprising 220,934 participants, Gao and colleagues evaluated daytime napping and nighttime sleeping durations in subsets of patients with established PD (n = 267), recent diagnosis of PD (n = 396), and in those who were in the prediagnostic PD stage (n = 770) and who only later converted. They reported that longer daytime napping was associated with higher odds of PD in all three clinical stages. This association was strongest for established PD (long nappers, i.e. ≥ 1 h, versus non-nappers OR 3.9; 95% CI: 2.8, 5.6; p < 0.0001) but also significant in the other cases (recent cases OR 2.2; 95% CI: 1.7, 3.0; p < 0.0001; prediagnostic cases OR 1.5; 95% CI: 1.2, 1.9; p = 0.0003). However, in nighttime sleep duration analysis, a U-shaped relation between hours of nighttime sleep and diagnosis of PD was observed for established cases, but was less apparent for recent cases and disappeared for prediagnostic cases. The authors therefore showed that daytime sleepiness—as expressed by daytime napping duration, but not nighttime sleep duration—is one of the early nonmotor symptoms of PD [39].

Daytime sleepiness in PD was first described many decades ago [1, 17, 40, 41], nonetheless it still remains an underappreciated feature despite its relevance, especially, for example, following reports of PD patients (taking dopamine agonists) falling asleep while driving [42]. Driving safety in patients with PD has been evaluated through driving simulators with studies reporting more total collisions in PD patients compared to controls [43, 44]. Studies using the Epworth sleepiness scale to evaluate daytime sleepiness in PD found varying abnormal scores (9.3% [45], 33% [1], or 43.2%) [46], with 28.4% noting somnolence with dopaminergic drug intake and 6.8% describing unintended sleep episodes [46].

However, the relationship between PD and daytime sleepiness is controversial, and a large study using the Epworth sleepiness scale conducted by the Parkinson’s Progression Markers Initiative (PPMI) group on 423 PD patients, reported no difference in prevalence of excessive sleepiness in de novo untreated PD patients compared with healthy controls [47]. A 3-year follow-up in this cohort showed that daytime sleepiness increases significantly over time in early PD, with a dose-dependent effect of dopaminergic therapy, suggesting a relevant role of PD-specific therapy more than underlying pathophysiological mechanisms for excessive daytime sleepiness in PD [48].

Sleep-related breathing disorders

Early reports showed large variability of sleep-related breathing disorders in PD, with some studies showing more central, others more obstructive, or no sleep-related breathing disorder at all, but in early studies these differences may have been due to less established methods of respiratory event recording during polysomnography (PSG) and small sample sizes.

Even in patients without a confirmed diagnosis of manifest sleep apnea a significant correlation between heavy snoring and daytime sleepiness has been reported for PD [1, 49]. One study showed that manifest or subclinical sleep breathing disorders are present in up to 50% of PD patients, but in contrast to non-PD patients sleep structure in PD is not normalized with CPAP treatment [50].

However, other studies have reported variable prevalence and severity of sleep-related breathing disorders in PD. Diederich and colleagues reported a 43% prevalence of sleep apnea syndrome in PD, which was, however, mostly mild or moderate with little decline of the minimal or mean oxygen saturation levels compared to an apnea–hypopnea index (AHI)-matched control group [51]. Arnulf and co-workers found sleep apnea (defined according to established criteria for moderate or severe obstructive sleep apnea) in 20% of 54 PD patients treated with levodopa or a combination of levodopa and dopamine agonists referred for sleepiness [52]. In another study the same group reported that sleep apnea in PD was less frequent than in controls, when this latter group was BMI-matched with hospitalized controls (27% vs. 40%), and only 10% of PD patients had severe sleep apnea [53]. Similarly, Trotti and Bliwise reported no increased risk of obstructive sleep apnea in PD compared to normative population-based data from the Sleep Heart Health Study. In this cohort, Epworth Sleepiness Scales scores, BMI, and snoring did not correlate with the AHI [54].

Further adding to the complexity of sleep disturbances in PD, these patients spend more time in the supine position and the presence of severe obstructive sleep apnea syndrome in PD is associated with a major reduction in position changes [55].

At least one study has shown that PD patients with obstructive sleep apnea have worse cognitive functioning on cognitive screening measures than those without, but again, CPAP-treatment may not result in overall cognitive improvement in patients with PD [56].

Based on these data, there is some discussion about whether obstructive sleep apnea is a problem in patients with PD, especially as common symptoms associated with sleep apnea, e.g. sleepiness, cognitive impairment, nocturia, and snoring have been reported to not be related with AHI in PD patients [53, 54]. These observations lead to questions about whether sleep apnea is a cause of sleepiness in PD patients and when is it clinically relevant [53, 57]. These concerns highlight the importance of a detailed sleep history and the need to perform adequate sleep studies in PD in order to account for all sleep disturbances. Nevertheless, even symptoms commonly associated with sleep apnea may not relate to AHI in PD; PD patients with relevant sleep apnea should be treated as a general rule due to probable long-term negative cardiovascular outcomes, although long-term comparative follow-up studies investigating cardiovascular outcomes in PD patients with treated and untreated sleep-related breathing disorders, are lacking [57].

Circadian disturbances

Regulation of sleep and wakefulness is a highly complex and integrated function involving multiple brain areas and neurotransmitters, many of which are impaired in PD [1,2,3,4,5,6,7]. Dopamine for example plays a key role in the circadian system, but its metabolism and activity are also strongly influenced by the circadian clock [6]. On this pathophysiological background it is not surprising that disturbances of sleep and wakefulness are almost ubiquitous in patients with PD. Moreover, impairment of circadian function in PD is relevant not only for sleep–wake cycles but also for motor, autonomic, cognitive, and psychiatric symptoms in PD patients [6].

Interestingly, some components of the circadian system seem to be preserved in PD. In a rat PD model with unilateral 6-hydroxy-dopamine lesions, it was shown that circadian distribution of motor activity is intact [58]. Circadian distribution of temperature rhythms is also maintained in PD, which is not the case in multiple system atrophy (MSA) [59]. However, increased sleepiness under treatment with dopamine agonists may also relate to an effect on body temperature (as described in 1999) [60, 61].

Despite these reports of preserved circadian distribution of motor activity pattern and temperature, on a clinical basis circadian disturbances are frequent in patients with PD [6, 7, 10, 62], and were noted as early as 1817 by James Parkinson [63]. It was later shown that circadian melatonin secretion rhythms are blunted in PD, and amplitude of melatonin rhythm is reduced [64]. These alterations in PD patients may also relate to both insufficient exposure to bright light [65,66,67] and phase advance of the sleep–wake cycle due to treatment with dopaminergic drugs [68, 69]. Moreover, it is conceivable that impulse control disorders, such as gambling, compulsive shopping, binge eating, compulsive sexual behavior, and punding, take place mainly during the nighttime or favor loosing track of time and therefore accompany circadian disruption or contribute to precipitating and perpetuating sleep–wake cycle disturbances. In clinical cases, this may lead to the inversion of the day- and nighttime rhythm, with insomnia after midnight and increased daytime sleepiness [70].

Interestingly, in a large case control study of Han Chinese patients, an association of single nucleotide polymorphisms in the clock genes ARNTL and PER1 was found in patients with PD, thus supporting the notion that genetic polymorphisms are present in these two circadian regulation genes [71].

Published evidence highlights the complexity and multifactorial nature of circadian rhythm disturbances in PD, which implies that an accurate clinical and instrumental (using e.g. actigraphy and polysomnography) evaluation is needed in these patients to identify the main cause or main problem in sleep–wake cycle impairment and provide individualized treatment.

Sleep-related movement disorders

Among sleep-related movement disorders, RLS and periodic leg movements of sleep (PLMS) have been particularly investigated in patients with PD and this aspect was recently reviewed by Högl and Stefani [72].

In the past three decades, multiple studies have attempted to evaluate the frequency of RLS in patients with PD producing very discrepant results ranging from 0% to 52.3% [12, 13, 72,73,74,75,76]. Together with these discrepancies, some authors noted early on that RLS diagnosis may be confounded in patients with PD due to potential overlap of RLS symptoms with early morning dystonia, akathisia, painful neuropathy, nocturnal hypokinesia (which may be associated with a reported urge to move), biphasic dyskinesia, and nocturnal legs cramps [12, 75, 76].

Interestingly, augmentation of RLS is present very rarely in patients with PD, probably because of a different underlying alteration in dopaminergic circuits in RLS (dopamine dysfunction) and PD (dopamine deficit), and different responses of these altered circuits to dopamine/dopaminergic therapy.

Frequency and causes of RLS in PD are still unclear. Angelini and co-workers investigated a series of 109 cognitively unimpaired de novo PD and compared them to age-matched and sex-matched controls. They found that there was no significant difference in overall lifetime and current primary RLS between PD patients and controls, but discussed whether the frequent onset of RLS symptoms after diagnosis of PD could be related to dopaminergic therapy for PD [77]. This hypothesis is supported by the reports that even in subjects with PLMS the use of dopaminergic agents might lead to the development of RLS [78].

Verbaan and co-workers evaluated the frequency and clinical profile of RLS in 269 non-demented PD patients and also reported a similar prevalence of RLS as in the general population [79].

Gjerstad and co-workers performed a study in 200 drug-naïve patients with early, untreated PD and 173 age-matched and gender-matched control subjects. They clearly reported that there was a three-fold higher risk of leg motor restlessness, but not of true RLS, in patients with early PD. 40.5% of PD patients and 17.9% of controls reported leg restlessness (p < 0.001), but only 15.5% of patients with PD and 9.2% of controls met criteria for full RLS (p = 0.07) [80]. Similar results were also reported by another group in a large sample of PD patients [81]. These data highlight the need for an accurate assessment of symptoms when suspecting RLS in PD patients in order to exclude potential mimics.

Only Cochen De Cock and colleagues evaluated the suggested immobilization test (SIT) in PD and reported that it is useful for making a diagnosis of RLS in patients with PD in whom the diagnosis of RLS based on expert interview alone may be difficult. The most sensitive instrument was the sensory part of the SIT that clearly showed an increase of sensory leg discomfort over time [82]. The PLM index was increased in patients with primary RLS compared to controls, but did not differ between patients with PD, with and without RLS [82].

Nocturnal akinesia, a well-known motor manifestation of PD, significantly diminishes the capacity to make comfort moves and can lead to sleep disruption [12]. Moreover, patients may report an urge to move due to nocturnal akinesia/hypokinesia. Lakke and colleagues have shown that axial rotation is even more disturbed in the recumbent position than while standing, which may lead to increase of symptoms due to hypokinesia at rest or during the night, mimicking RLS symptoms [83].

Impaired turning ability in bed has been associated with sleep disturbances [84]. Louter and co-workers evaluated a PD cohort prospectively and found that patients who subjectively reported impaired bed mobility (i.e., nocturnal hypokinesia), indeed showed fewer sleep-related body position changes than controls, and that polysomnographically evaluated sleep efficiency was diminished in these patients [85]. This should be taken into account when treating motor symptoms in PD patients, as a study from Thailand has shown that in PD patients with nocturnal hypokinesia/akinesia, nighttime apomorphine infusion improves the number of turns in bed, turning velocity, and the extension of turning as measured by actigraphy [86].

RBD and other parasomnias

In patients with PD, beyond the well-known and peculiar occurrence of REM sleep behavior disorder (RBD), non-REM-sleep parasomnias (e.g. sleepwalking) and parasomnia overlap disorder have also been described.

Bassetti and co-workers systematically investigated the presence of sleepwalking in 165 consecutive PD patients. 3.6% (n = 6) reported adult-onset sleepwalking. In 4 out of 6 patients, RBD was detected on video-polysomnography [87]. In another study, video-polysomnography (vPSG) was used to assess 30 patients with PD (10 of them with a history of sleepwalking, 10 with a history of RBD and 10 without a history of parasomnia). Again, 8 out of 10 patients with a history of sleepwalking presented RBD on vPSG. Sleepwalking in this cohort was associated with depression, higher disease severity, and functional disability. Due to the frequent occurrence of overlap parasomnia, the authors suggested that a common underlying disturbance of motor control during sleep exists in PD [88].

The diagnostic criteria for RBD comprise repeated episodes of sleep-related vocalization and/or complex motor behaviors, and these behaviors need to be documented by PSG as occurring during REM sleep, or, based on a clinical history of dreaming, are presumed to occur during REM sleep. In addition, it is obligatory that polysomnographic recording demonstrates REM sleep without atonia [89]. Other sleep-related movement disorders that are frequent in PD (e.g. PLMS, sleep apnea) might produce similar symptoms mimicking RBD by history and need to be excluded.

RBD affects up to 47% of patients with PD [90,91,92,93]. In the past RBD has received much attention due to the fact that it may precede PD by more than a decade [93,94,95,96,97,98,99], but there is also the possibility that RBD onset is more or less simultaneous with PD onset or that RBD follows PD onset by several years [91, 100].

In fact, the remarkably high rate of conversion from isolated RBD into alpha synuclein disease, namely PD, dementia with Lewy bodies, or rarely MSA, has led several authors to suggest here that RBD itself needs to be considered more than a REM-parasomnia, as it represents an alpha synuclein disease or an early manifestation of alpha synuclein disease [94, 97, 101]. For clinical studies, combinations of isolated RBD with other Parkinson/alpha-synuclein-related neurodegeneration risk markers is probably the most useful approach. Multiple biomarkers of alpha synuclein-related neurodegeneration have been described [93], and may serve to evaluate different aspects of neurodegeneration, and while some, such as olfactory dysfunction, are stable markers indicating a higher risk of short-term conversion, others such as DAT-SPECT are progressive markers useful for monitoring disease progression over time [93].

The International Parkinson and Movement Disorder Society has calculated that the PSG-confirmed likelihood ratio of more than 80% probability of suffering of prodromal PD is 130 in patients with isolated (previously called “idiopathic“) RBD [102]. However, this is true and has been extensively confirmed only for vPSG confirmed RBD. In fact, likelihood ratio declines to 2.3 in case of positive response to a screening test for RBD with documented specificity of 80–99% [102]. These is even more relevant considering that an increasing amount of studies reported lower specificity of validated questionnaires for RBD outside the context of validation studies [103,104,105,106,107].

Interestingly, there is increasing evidence that there may be prodromal stages of RBD, which manifest as minor jerks [91, 100, 108, 109] or REM sleep without atonia [101]. Mollenhauer and co-workers found that even PD patients who did not yet meet the criteria for RBD had more movement during REM sleep [91], and Sixel-Döring and Trenkwalder denominated these seemingly purposeful movements “REM sleep behavioral events” (RBE) and demonstrated that they could represent another prodromal sign of RBD [100, 108].

Dream content was investigated in PD as early as 1992 [110]. Later on, Borek and colleagues investigated dream content in PD with and without RBD, showing that violent and aggressive dreams were more common in RBD patients, and that men with PD had more aggressive dreams than women with PD [111]. The same group further evaluated aggressive dream content in men with PD and searched for a correlation with testosterone levels, which was not found [112].

Bugalho and Paiva characterized dream content in PD in detail using the Hall and van de Castle system. They found more dreams with animals, aggression/friendliness, physical aggression, befriender in PD compared to controls, and less aggressor and bodily misfortunes features [113]. Valli and colleagues further analyzed dreams in patients with PD and RBD systematically, using spontaneous free-worded dream reports and a structured dream questionnaire during vPSG. Those data could be linked to motor behaviors on vPSG above chance level [114]. Interestingly, another study by the same group assessed dream content analysis in PD with and without RBD and reported no major differences between these two groups regarding action-filledness, vividness, or threat content. However, negative dreams were more frequent in PD with RBD compared to PD without RBD [115].

Dream content has also been investigated in the prodromal phase of RBD. Most patients with RBE can recall dream content, and report nonviolent, non-threatening dreams. RBE subjects who at follow-up developed RBD reported more vivid and elaborate dreams [109].

Sleep benefit and positive effect of sleep deprivation in patients with PD

The complex interaction of sleep and motor function is reflected in two interesting phenomena: sleep benefit, i.e. the experience of an improvement of motor function upon awakening [15,16,17,18,19], and a positive effect of sleep deprivation on motor function [20,21,22].

Sleep benefit was first described based on patients’ reports, and systematically evaluated in large cohorts of patients with PD with contrasting results. Some groups reported this phenomenon to be common in a subgroup of PD patients with specific clinical characteristics, e.g. with longer disease duration [17] and younger age at onset of disease [19, 116]. This phenomenon has been reported to be so relevant to allow PD patients with sleep benefit to skip or delay medication [18]. A study systematic evaluating motor state a night before sleep and in the morning upon awakening reported a slight motor improvement in the morning in patients with sleep benefit, without polysomnographic differences between the two groups [15]. Another study using PSG reported shorter total sleep times and longer sleep latencies in PD patients reporting sleep benefit [117].

However, other groups found no actual improvement in motor functioning in PD patients reporting sleep benefit [118, 119], or only in a small percentage of them [120, 121], or reported in those patients with PD experiencing sleep benefit no association with the previously reported clinical variables [122], maybe because of methodological issues.

Interestingly, in patients with PD it has also been described, for the first time as early as 1987 [22], a motor improvement after sleep deprivation. These observations have been later on replicated [20], but could not be confirmed in a controlled study. These latter results suggested that only a subgroup of PD patients could benefit from partial sleep deprivation [21].

Assessment of sleep disturbances in patients with PD

In general, a comprehensive sleep history is often a very useful first step to narrow down the type of sleep disorders in patients with PD. It should start with the time when the patient goes to bed and gets up and also include planned daytime naps. It should involve the perceived sleep latency, perceived awakenings (including prolonged wake phases during the nighttime and daytime dosing of/or fighting against sleepiness). The Epworth sleepiness scale or other scales can be used [123].

Specifically, the evaluation of insomnia should rule out sleep hygiene or circadian disorders. Patients should be questioned specifically about the presence of impulse control disorders and nighttime activities, particularly in case of suspected circadian rhythm disturbances. If a circadian disorder, such as delayed or advanced sleep phase syndrome or non-24-h sleep–wake disorder is suspected, assessments with actigraphy or dim light melatonin onset may prove useful [124].

For patients with prominent daytime sleepiness, polysomnography should be used in every case (to rule out sleep disordered breathing), but a multiple sleep latency test (for instance to demonstrate a narcolepsy-like phenotype and to quantify the amount of daytime sleepiness) is also warranted [124].

Respiration questioning should at least include snoring and witness apneas, positional dependence, breathing pauses, intensity of snoring, nocturnal hypertranspiration or nocturia. In specific cases stridor (which is for patients relatively difficult to distinguish from simple snoring) should also be assessed. If underlying sleep disordered breathing is suspected, cardiorespiratory polygraphy or polysomnography should be performed [124].

Every attempt should be made to assess the presence of RLS, and distinguish it from other types of restlessness, specifically investigating possible mimics or confounders. Patients should be asked about the ability to turn in bed. Polysomnography is not needed to make a diagnosis of RLS, and in patients with PD PLM are very frequent [72, 125]. In case of suspected RLS, an extensive clinical history is fundamental to rule out possible mimics which are very common in PD patients, these include nocturnal hypokinesia/akinesia (sometimes associated with an urge to move), akathisia, nocturnal leg cramps, early morning dystonia, and painful neuropathy. In addition, medication-induced dyskinesias could be mistaken for RLS-related PLM.

For patients with suspected RBD, vPSG is required, also if the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [126], in contrast to the ICSD-3 [33], does not require polysomnographic demonstration of REM sleep without atonia if there is a history suggestive of RBD in patients with an established synucleinopathy diagnosis. However, it is likely that performance of vPSG would diagnose more patients with RBD, in whom history taking alone was not sensitive [93, 127, 128] or also rule out mimics in subjects with an apparently “clear” history of RBD, such as obstructive sleep apnea which may go along with violent behavioral releases [129] and violent PLM [130].

Patients should be specifically investigated for altered dream content, dream enactment with movements or jerks, and vocalizations, specifically highly variable vocalizations for RBD [124]. In general, current treatment should be assessed due to potential side effects or influence on sleep disorders.

Several questionnaires have been developed and validated for patients with PD [123]. The International Movement Disorder Society (MDS) task force recommends, for overall sleep disturbance, both the Parkinson’s Disease Sleep Scale (PDSS) [131] and Scales for Outcomes in PD Sleep (SCOPA sleep), as well as two generic scales, namely the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale [123, 132].

Specific questionnaires for specific sleep disorders, such as for RBD, have also been developed [93]. In general, they have the advantage of being used to screen the general population or large samples of study populations without performing a vPSG. However, they cannot usually be used as diagnostic instruments and e.g. for RBD questionnaires several limitations have been demonstrated [93, 103,104,105,106,107, 127]. Actigraphy is also useful as a first screening method to potentially indicate suspected RBD [133].

However, in the evaluation of patients with abnormal daytime sleepiness, and with suspected RBD, vPSG evaluation is indispensable. Also, if there is some treatment-refractory sleep disturbance, or if one suspects multiple contributors and comorbid sleep disorders, vPSG will help to narrow down the differential diagnostic possibilities.

Due to the multifactorial aspects of sleep disorders in patients with PD, vPSG will often provide much more detailed, objective, and quantifiable information about the underlying aspects of the sleep disorder in an individual patient, and at the same time provide information about sleep integrity or fragmentation, the number of arousals or awakenings, the total sleep efficiency, respiration during sleep and respiratory events, and the quantification of motor activity during sleep, ranging from REM sleep without atonia (RWA)/RBD to PLM, fragmentary myoclonus [72, 134] and others. vPSG in patients with PD should in every case include not only the usual EMG channels of mental/submental muscles and tibial anterior muscles, but also of upper extremity muscles (flexor digitorum superficialis from both arms). This is not only recommended based on normative values provided by the SINBAR group [135] but also provides more sensitivity and specificity than using EMG alone [136].

Treatment of sleep disorders in patients with Parkinson’s disease

From the manifold clinical manifestations and underlying pathomechanisms of sleep disorders in patients with PD outlined above, it is obvious that treatment needs to be tailored individually according to the predominant clinical symptomatology and underlying specific sleep-related diagnosis. However, a major problem is the sparsity of randomized, controlled trials for sleep disorders in PD.

For treatment of insomnia in patients with PD, hypnotics are sometimes indicated, but the caveats of potential worsening of daytime sleepiness or sleep-related breathing disorders should be kept in mind. Clinically, quetiapine is sometimes used, and in cases of very severe insomnia clozapine—with the usual treatment caveats—have been used. Melatonin treatment is not specifically indicated for insomnia in PD, but is often used for RBD (see below). Rotigotine has been reported to improve sleep quality and continuity in PD patients by promoting sleep stability and increasing REM [137]. However, in general, there is insufficient evidence on drugs to treat insomnia in PD patients, although eszoplicone and melatonin are considered “possibly useful”. Some authors maintain that cognitive behavioral treatment for insomnia, as in patients without PD, may be useful [138]. To treat daytime sleepiness in PD, caffeine [139, 140], and modafinil can be used.

Regarding treatment of sleep-related breathing disorders, there is some controversy. If sleep apnea is moderate or severe, positive airway pressure therapy for PD patients can be indicated [141]. However, the response to this treatment regarding improvement of sleep structure or daytime sleepiness is less clear than in patients without PD [50]. Motor impairment often makes handling of the CPAP device difficult for patients with PD. Intraoral devices as an alternative treatment for certain patients with obstructive sleep apnea may also be limited in those with abnormal salivation or oro-facial dyskinesias.

For treatment of circadian disorders, light therapy shows promising outcomes on sleep and alertness in PD, with beneficial effects on sleep, mood, and other non-motor symptoms in PD [66, 142,143,144].

As prospective treatment studies for RLS co-existing with PD are missing, most commonly used medications in the PD population are the same as in the general RLS population, namely dopamine agonists, calcium channel alpha-2-delta ligands, clonazepam, and opioids [145,146,147]. As dopamine agonists and levodopa are already used to treat motor symptoms in PD, adjustments in timing of intake depending on time of appearance of RLS symptoms may be beneficial. Iron supplementation should be considered if ferritin levels are low [148]. Medication known to exacerbate RLS (e.g. dopamine blockers, anti-cholinergic, and anti-histaminic agents) should be discontinued if possible.

Treatment of REM sleep behavior disorder should first include safety measures to ensure maximum safety in the sleeping environment. Such measures may include removing any objects close to the bed that may cause injuries during dream enactment, or making adjustments by moving furniture or using pillows to cover furniture, walls, and the floor. Bed partners should be advised to sleep separately. Medications which potentially aggravate RBD (e.g. antidepressants) should be eliminated if possible [149]. A bed alarm has been shown to be beneficial for RBD in preliminary studies [150]. Rotigotine was also shown to improve RBD in a vPSG study [151]. A double-blind, crossover pilot trial in 12 patients reported a reduction in frequency of RBD episodes (as reported by diaries of bed partners) with rivastigmine [152]. Effective pharmacological treatment based on case reports and series include clonazepam and melatonin, but double-blind, placebo-controlled trials are missing [93, 142, 147].

Future research directions

Sleep and regulation of sleep and wakefulness are relevant aspects in patients with Parkinson’s disease. Disorders of sleep and wakefulness in Parkinson’s disease are often reported, and comprise the full spectrum of sleep disorder categories. However, for most of them there are discordant data in the literature and treatment studies specifically conducted on patients with Parkinson’s disease are mostly missing. Therefore, these aspects should be further clarified in future studies. Specifically, open issues with discordant data such as relevance of restless legs syndrome and sleep apnea in Parkinson’s disease should be disentangled. Moreover, disturbances of circadian rhythm are very relevant in those patients and deserve more attention and investigations as their recognition and treatment might relevantly improve quality of life of patients with Parkinson’s disease. Other less understood aspects like sleep benefit and effect of sleep deprivation need to be further investigated.

Funding and disclosure

The authors declare no competing interests.


  1. 1.

    Hogl B, Seppi K, Brandauer E, et al. Increased daytime sleepiness in Parkinson’s disease: a questionnaire survey. Mov Disord. 2003;18:319–23.

    Article  Google Scholar 

  2. 2.

    Trenkwalder C, Hogl B. Sleep in Parkinson syndromes. Handb Clin Neurol. 2007;83:365–76.

    Article  Google Scholar 

  3. 3.

    Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci. 2017;18:435–50.

    Article  CAS  Google Scholar 

  4. 4.

    Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009;8:464–74.

    Article  CAS  Google Scholar 

  5. 5.

    Freeman AAH. Neurochemistry of the sleep–wake cycle in Parkinson’s disease. In: Videnovic A, Högl B, editors. Disorders of sleep and circadian rhythms in Parkinson’s disease. Vienna: Springer Vienna; 2015. p. 19–33.

  6. 6.

    Videnovic A, Lazar AS, Barker RA, Overeem S. ‘The clocks that time us’—circadian rhythms in neurodegenerative disorders. Nat Rev Neurol. 2014;10:683–93.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Videnovic A, Golombek D. Circadian and sleep disorders in Parkinson’s disease. Exp Neurol. 2013;243:45–56.

    Article  Google Scholar 

  8. 8.

    Lees AJ, Blackburn NA, Campbell VL. The nighttime problems of Parkinson’s disease. Clin Neuropharmacol. 1988;11:512–9.

    Article  CAS  Google Scholar 

  9. 9.

    Poewe W, Hogl B. Parkinson’s disease and sleep. Curr Opin Neurol. 2000;13:423–6.

    Article  CAS  Google Scholar 

  10. 10.

    Chahine LM, Amara AW, Videnovic A. A systematic review of the literature on disorders of sleep and wakefulness in Parkinson’s disease from 2005 to 2015. Sleep Med Rev. 2017;35:33–50.

    Article  Google Scholar 

  11. 11.

    Videnovic A, Comella CL. Sleep disorders in Parkinson’s disease. Handb Clin Neurol. 2011;99:997–1010.

    Article  Google Scholar 

  12. 12.

    Poewe W, Högl B. Akathisia, restless legs and periodic limb movements in sleep in Parkinson’s disease. Neurology. 2004;63:S12–6.

    Article  Google Scholar 

  13. 13.

    Peralta CM, Frauscher B, Seppi K, et al. Restless legs syndrome in Parkinson’s disease. Mov Disord. 2009;24:2076–80.

    Article  Google Scholar 

  14. 14.

    Oertel W, Deuschl G, Poewe W. Parkinson-Syndrome und andere Bewegungsstörungen. Germany: Thieme Georg Verlag; 2011.

  15. 15.

    Hogl BE, Gomez-Arevalo G, Garcia S, et al. A clinical, pharmacologic, and polysomnographic study of sleep benefit in Parkinson’s disease. Neurology. 1998;50:1332–9.

    Article  CAS  Google Scholar 

  16. 16.

    Hogl B, Gershanik O. Sleep benefit in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2000;68:798–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Tandberg E, Larsen JP, Karlsen K. Excessive daytime sleepiness and sleep benefit in Parkinson’s disease: a community-based study. Mov Disord. 1999;14:922–7.

    Article  CAS  Google Scholar 

  18. 18.

    Merello M, Hughes A, Colosimo C, Hoffman M, Starkstein S, Leiguarda R. Sleep benefit in Parkinson’s disease. Mov Disord. 1997;12:506–8.

    Article  CAS  Google Scholar 

  19. 19.

    Currie LJ, Bennett JP Jr, Harrison MB, Trugman JM, Wooten GF. Clinical correlates of sleep benefit in Parkinson’s disease. Neurology. 1997;48:1115–7.

    Article  CAS  Google Scholar 

  20. 20.

    Reist C, Sokolski KN, Chen CC, Coskinas E, Demet EM. The effect of sleep deprivation on motor impairment and retinal adaptation in Parkinson’s disease. Prog Neuro-Psychopharmacol Biol Psychiatry. 1995;19:445–54.

    Article  CAS  Google Scholar 

  21. 21.

    Hogl B, Peralta C, Wetter TC, Gershanik O, Trenkwalder C. Effect of sleep deprivation on motor performance in patients with Parkinson’s disease. Mov Disord. 2001;16:616–21.

    Article  CAS  Google Scholar 

  22. 22.

    Bertolucci PH, Andrade LA, Lima JG, Carlini EA. Total sleep deprivation and Parkinson disease. Arq Neuro-Psiquiatr. 1987;45:224–30.

    Article  CAS  Google Scholar 

  23. 23.

    Pont-Sunyer C, Iranzo A, Gaig C, et al. Sleep disorders in Parkinsonian and nonParkinsonian LRRK2 mutation carriers. PLoS ONE. 2015;10:e0132368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    O’Dowd S, Galna B, Morris R, et al. Poor sleep quality and progression of gait impairment in an incident Parkinson’s disease cohort. J Parkinson’s Dis. 2017;7:465–70.

    Article  Google Scholar 

  25. 25.

    Emser W, Brenner M, Stober T, Schimrigk K. Changes in nocturnal sleep in Huntington’s and Parkinson’s disease. J Neurol. 1988;235:177–9.

    Article  CAS  Google Scholar 

  26. 26.

    Myslobodsky M, Mintz M, Ben-Mayor V, Radwan H. Unilateral dopamine deficit and lateral eeg asymmetry: sleep abnormalities in hemi-Parkinson’s patients. Electroencephalogr Clin Neurophysiol. 1982;54:227–31.

    Article  CAS  Google Scholar 

  27. 27.

    Comella CL, Tanner CM, Ristanovic RK. Polysomnographic sleep measures in Parkinson’s disease patients with treatment-induced hallucinations. Ann Neurol. 1993;34:710–4.

    Article  CAS  Google Scholar 

  28. 28.

    Puca FM, Bricolo A, Turella G. Effect of L-dopa or amantadine therapy on sleep spindles in Parkinsonism. Electroencephalogr Clin Neurophysiol. 1973;35:327–30.

    Article  CAS  Google Scholar 

  29. 29.

    Christensen JA, Nikolic M, Warby SC, et al. Sleep spindle alterations in patients with Parkinson’s disease. Front Hum Neurosci. 2015;9:233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Kendel K, Saprianov G, Graf B. Wach-EEG und Schlaf-EEG beim Parkinson-Syndrom. Akt Neurol. 1974;1:125–36.

  31. 31.

    Happe S, Anderer P, Pirker W, et al. Sleep microstructure and neurodegeneration as measured by [123I]beta-CIT SPECT in treated patients with Parkinson’s disease. J Neurol. 2004;251:1465–71.

    Article  Google Scholar 

  32. 32.

    Brunner H, Wetter TC, Hogl B, Yassouridis A, Trenkwalder C, Friess E. Microstructure of the non-rapid eye movement sleep electroencephalogram in patients with newly diagnosed Parkinson’s disease: effects of dopaminergic treatment. Mov Disord. 2002;17:928–33.

    Article  Google Scholar 

  33. 33.

    American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic & coding manual (ICSD-3). 3rd ed. Westchester, IL: American Academy of Sleep Medicine; 2014.

  34. 34.

    Gjerstad MD, Wentzel-Larsen T, Aarsland D, Larsen JP. Insomnia in Parkinson’s disease: frequency and progression over time. J Neurol Neurosurg Psychiatry. 2007;78:476–9.

    Article  CAS  Google Scholar 

  35. 35.

    Tholfsen LK, Larsen JP, Schulz J, Tysnes OB, Gjerstad MD. Changes in insomnia subtypes in early Parkinson disease. Neurology. 2017;88:352–8.

    Article  Google Scholar 

  36. 36.

    Zhu K, van Hilten JJ, Marinus J. The course of insomnia in Parkinson’s disease. Parkinson Relat Disord. 2016;33:51–7.

    Article  Google Scholar 

  37. 37.

    Joy SP, Sinha S, Pal PK, Panda S, Philip M, Taly AB. Alterations in polysomnographic (PSG) profile in drug-naive Parkinson’s disease. Ann Indian Acad Neurol. 2014;17:287–91.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Ferreira T, Prabhakar S, Kharbanda PS. Sleep disturbances in drug naive Parkinson’s disease (PD) patients and effect of levodopa on sleep. Ann Indian Acad Neurol. 2014;17:416–9.

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Gao J, Huang X, Park Y, et al. Daytime napping, nighttime sleeping, and Parkinson disease. Am J Epidemiol. 2011;173:1032–8.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Tandberg E, Larsen JP, Karlsen K. A community-based study of sleep disorders in patients with Parkinson’s disease. Mov Disord. 1998;13:895–9.

    Article  CAS  Google Scholar 

  41. 41.

    Factor SA, McAlarney T, Sanchez-Ramos JR, Weiner WJ. Sleep disorders and sleep effect in Parkinson’s disease. Mov Disord. 1990;5:280–5.

    Article  CAS  Google Scholar 

  42. 42.

    Frucht S, Rogers JD, Greene PE, Gordon MF, Fahn S. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology. 1999;52:1908–10.

    Article  CAS  Google Scholar 

  43. 43.

    Hauser RA, Gauger L, Anderson WM, Zesiewicz TA. Pramipexole-induced somnolence and episodes of daytime sleep. Mov Disord. 2000;15:658–63.

    Article  CAS  Google Scholar 

  44. 44.

    Zesiewicz TA, Cimino CR, Malek AR, et al. Driving safety in Parkinson’s disease. Neurology. 2002;59:1787–8.

    Article  CAS  Google Scholar 

  45. 45.

    Ylikoski A, Martikainen K, Sarkanen T, Partinen M. Parkinson’s disease and narcolepsy-like symptoms. Sleep Med. 2015;16:540–4.

    Article  Google Scholar 

  46. 46.

    Monaca C, Duhamel A, Jacquesson JM, et al. Vigilance troubles in Parkinson’s disease: a subjective and objective polysomnographic study. Sleep Med. 2006;7:448–53.

    Article  CAS  Google Scholar 

  47. 47.

    Simuni T, Caspell-Garcia C, Coffey C, et al. Correlates of excessive daytime sleepiness in de novo Parkinson’s disease: a case control study. Mov Disord. 2015;30:1371–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Amara AW, Chahine LM, Caspell-Garcia C, et al. Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2017;88:653–62.

    Article  Google Scholar 

  49. 49.

    Braga-Neto P, da Silva-Junior FP, Sueli Monte F, de Bruin PF, de Bruin VM. Snoring and excessive daytime sleepiness in Parkinson’s disease. J Neurol Sci. 2004;217:41–5.

    Article  Google Scholar 

  50. 50.

    Schäfer D. Schlafbezogene Atmungsstörungen bei Parkinsonsyndromen: Häufigkeit. Art Behandlätze. 2001;5:103–14.

    Google Scholar 

  51. 51.

    Diederich NJ, Vaillant M, Leischen M, et al. Sleep apnea syndrome in Parkinson’s disease. A case-control study in 49 patients. Mov Disord. 2005;20:1413–8.

    Article  Google Scholar 

  52. 52.

    Arnulf I, Konofal E, Merino-Andreu M, et al. Parkinson’s disease and sleepiness: an integral part of PD. Neurology. 2002;58:1019–24.

    Article  CAS  Google Scholar 

  53. 53.

    Cochen De Cock V, Abouda M, Leu S, et al. Is obstructive sleep apnea a problem in Parkinson’s disease? Sleep Med. 2010;11:247–52.

    Article  Google Scholar 

  54. 54.

    Trotti LM, Bliwise DL. No increased risk of obstructive sleep apnea in Parkinson’s disease. Mov Disord. 2010;25:2246–9.

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Cochen De Cock V, Benard-Serre N, Driss V, et al. Supine sleep and obstructive sleep apnea syndrome in Parkinson’s disease. Sleep Med. 2015;16:1497–501.

    Article  Google Scholar 

  56. 56.

    Harmell AL, Neikrug AB, Palmer BW, et al. Obstructive sleep apnea and cognition in Parkinson’s disease. Sleep Med. 2016;21:28–34.

    Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Hogl B. Sleep apnea in Parkinson’s disease: when is it significant? Sleep Med. 2010;11:233–5.

    Article  Google Scholar 

  58. 58.

    Baier PC, Branisa P, Koch R, Schindehutte J, Paulus W, Trenkwalder C. Circadian distribution of motor-activity in unilaterally 6-hydroxy-dopamine lesioned rats. Exp Brain Res. 2006;169:283–8.

    Article  CAS  Google Scholar 

  59. 59.

    Pierangeli G, Provini F, Maltoni P, et al. Nocturnal body core temperature falls in Parkinson’s disease but not in multiple-system atrophy. Mov Disord. 2001;16:226–32.

    Article  CAS  Google Scholar 

  60. 60.

    Boulay D, Depoortere R, Rostene W, Perrault G, Sanger DJ. Dopamine D3 receptor agonists produce similar decreases in body temperature and locomotor activity in D3 knock-out and wild-type mice. Neuropharmacology. 1999;38:555–65.

    Article  CAS  Google Scholar 

  61. 61.

    Boulay D, Depoortere R, Perrault G, Borrelli E, Sanger DJ. Dopamine D2 receptor knock-out mice are insensitive to the hypolocomotor and hypothermic effects of dopamine D2/D3 receptor agonists. Neuropharmacology. 1999;38:1389–96.

    Article  CAS  Google Scholar 

  62. 62.

    Videnovic A, Willis GL. Circadian system—a novel diagnostic and therapeutic target in Parkinson’s disease? Mov Disord. 2016;31:260–9.

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Parkinson J. An essay on the shaking palsy. London: Whittingham and Rowland; 1817.

  64. 64.

    Videnovic A, Noble C, Reid KJ, et al. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease. JAMA Neurol. 2014;71:463–9.

    Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Martin JL, Ancoli-Israel S. Sleep disturbances in long-term care. Clin Geriatr Med. 2008;24:39–50.

    Article  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Videnovic A, Klerman EB, Wang W, Marconi A, Kuhta T, Zee PC. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: a randomized clinical trial. JAMA Neurol. 2017;74:411–8.

    Article  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Hogl B. Circadian rhythms and chronotherapeutics—underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74:387–8.

    Article  Google Scholar 

  68. 68.

    Garcia-Borreguero D, Larrosa O, Bravo M. Parkinson’s disease and sleep. Sleep Med Rev. 2003;7:115–29.

    Article  Google Scholar 

  69. 69.

    Garcia-Borreguero D, Serrano C, Larrosa O, Granizo JJ. Circadian effects of dopaminergic treatment in restless legs syndrome. Sleep Med. 2004;5:413–20.

    Article  Google Scholar 

  70. 70.

    Djamshidian A, Poewe W, Hogl B. Impact of impulse control disorders on sleep–wake regulation in Parkinson’s disease. Parkinson’s Dis. 2015;2015:970862

    Google Scholar 

  71. 71.

    Gu Z, Wang B, Zhang YB, et al. Association of ARNTL and PER1 genes with Parkinson’s disease: a case-control study of Han Chinese. Sci Rep. 2015;5:15891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Hogl B, Stefani A. Restless legs syndrome and periodic leg movements in patients with movement disorders: specific considerations. Mov Disord. 2017;32:669–81.

    Article  Google Scholar 

  73. 73.

    Nomura T, Inoue Y, Miyake M, Yasui K, Nakashima K. Prevalence and clinical characteristics of restless legs syndrome in Japanese patients with Parkinson’s disease. Mov Disord. 2006;21:380–4.

    Article  Google Scholar 

  74. 74.

    Nomura T, Inoue Y, Nakashima K. Clinical characteristics of restless legs syndrome in patients with Parkinson’s disease. J Neurol Sci. 2006;250:39–44.

    Article  Google Scholar 

  75. 75.

    Ondo WG, Vuong KD, Jankovic J. Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol. 2002;59:421–4.

    Article  Google Scholar 

  76. 76.

    Iranzo A, Comella CL, Santamaria J, Oertel W. Restless legs syndrome in Parkinson’s disease and other neurodegenerative diseases of the central nervous system. Mov Disord. 2007;22(Suppl 18):S424–30.

    Article  Google Scholar 

  77. 77.

    Angelini M, Negrotti A, Marchesi E, Bonavina G, Calzetti S. A study of the prevalence of restless legs syndrome in previously untreated Parkinson’s disease patients: absence of co-morbid association. J Neurol Sci. 2011;310:286–8.

    Article  Google Scholar 

  78. 78.

    Santamaria J, Iranzo A, Tolosa E. Development of restless legs syndrome after dopaminergic treatment in a patient with periodic leg movements in sleep. Sleep Med. 2003;4:153–5.

    Article  Google Scholar 

  79. 79.

    Verbaan D, van Rooden SM, van Hilten JJ, Rijsman RM. Prevalence and clinical profile of restless legs syndrome in Parkinson’s disease. Mov Disord. 2010;25:2142–7.

    Article  Google Scholar 

  80. 80.

    Gjerstad MD, Tysnes OB, Larsen JP. Increased risk of leg motor restlessness but not RLS in early Parkinson disease. Neurology. 2011;77:1941–6.

    Article  CAS  Google Scholar 

  81. 81.

    Suzuki K, Okuma Y, Uchiyama T, et al. Characterizing restless legs syndrome and leg motor restlessness in patients with Parkinson’s disease: a multicenter case-controlled study. Parkinsonism Relat Disord. 2017;44:18–22.

    Article  Google Scholar 

  82. 82.

    De Cock VC, Bayard S, Yu H, et al. Suggested immobilization test for diagnosis of restless legs syndrome in Parkinson’s disease. Mov Disord. 2012;27:743–9.

    Article  Google Scholar 

  83. 83.

    Lakke JP, van Weerden TW, Staal-Schreinemachers A. Axial apraxia, a distinct phenomenon. Clin Neurol Neurosurg. 1984;86:291–4.

    Article  CAS  Google Scholar 

  84. 84.

    Stack EL, Ashburn AM. Impaired bed mobility and disordered sleep in Parkinson’s disease. Mov Disord. 2006;21:1340–2.

    Article  Google Scholar 

  85. 85.

    Louter M, van Sloun RJ, Pevernagie DA, et al. Subjectively impaired bed mobility in Parkinson disease affects sleep efficiency. Sleep Med. 2013;14:668–74.

    Article  Google Scholar 

  86. 86.

    Bhidayasiri R, Sringean J, Anan C, Boonpang K, Thanawattano C, Ray Chaudhuri K. Quantitative demonstration of the efficacy of night-time apomorphine infusion to treat nocturnal hypokinesia in Parkinson’s disease using wearable sensors. Parkinsonism Relat Disord. 2016;33(Suppl 1):S36–s41.

    Article  Google Scholar 

  87. 87.

    Poryazova R, Waldvogel D, Bassetti CL. Sleepwalking in patients with Parkinson disease. Arch Neurol. 2007;64:1524–7.

    Article  Google Scholar 

  88. 88.

    Di Fabio N, Poryazova R, Oberholzer M, Baumann CR, Bassetti CL. Sleepwalking, REM sleep behaviour disorder and overlap parasomnia in patients with Parkinson’s disease. Eur Neurol. 2013;70:297–303.

    Article  Google Scholar 

  89. 89.

    American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic and coding manual. 3rd ed. Rev. ed. Darien, IL: American Academy of Sleep Medicine; 2014.

  90. 90.

    Wetter TC, Trenkwalder C, Gershanik O, Högl B. Polysomnographic measures in Parkinson’s disease: a comparison between patients with and without REM sleep disturbances. Wien Klin Wochenschr. 2001;113:249–53.

    CAS  PubMed  Google Scholar 

  91. 91.

    Mollenhauer B, Trautmann E, Sixel-Doring F, et al. Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology. 2013;81:1226–34.

    Article  Google Scholar 

  92. 92.

    Boeve BF, Silber MH, Ferman TJ, Lucas JA, Parisi JE. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov Disord. 2001;16:622–30.

    Article  CAS  Google Scholar 

  93. 93.

    Hogl B, Stefani A, Videnovic A. Idiopathic REM sleep behaviour disorder and neurodegeneration—an update. Nat Rev Neurol. 2018;14:40–55.

    Article  Google Scholar 

  94. 94.

    Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013;14:744–8.

    Article  Google Scholar 

  95. 95.

    Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996;46:388–93.

    Article  CAS  Google Scholar 

  96. 96.

    Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009;72:1296–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Iranzo A, Molinuevo JL, Santamaria J, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006;5:572–7.

    Article  Google Scholar 

  98. 98.

    Iranzo A, Tolosa E, Gelpi E, et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013;12:443–53.

    Article  Google Scholar 

  99. 99.

    Galbiati A, Verga L, Giora E, Zucconi M, Ferini-Strambi L. The risk of neurodegeneration in REM sleep behavior disorder: a systematic review and meta-analysis of longitudinal studies. Sleep Med Rev. 2019;43:37–46.

    Article  Google Scholar 

  100. 100.

    Sixel-Doring F, Zimmermann J, Wegener A, Mollenhauer B, Trenkwalder C. The evolution of REM sleep behavior disorder in early Parkinson disease. Sleep. 2016;39:1737–42.

    Article  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Stefani A, Gabelia D, Hogl B, et al. Long-term follow-up investigation of isolated rapid eye movement sleep without atonia without rapid eye movement sleep behavior disorder: a pilot study. J Clin Sleep Med. 2015;11:1273–9.

    Article  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord. 2015;30:1600–11.

    Article  Google Scholar 

  103. 103.

    Stefani A, Mahlknecht P, Seppi K, et al. Consistency of “Probable RBD” diagnosis with the RBD screening questionnaire: a follow-up study. Mov Disord Clin Pract. 2017;4:403–5.

    Article  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Stiasny-Kolster K, Sixel-Doring F, Trenkwalder C, et al. Diagnostic value of the REM sleep behavior disorder screening questionnaire in Parkinson’s disease. Sleep Med. 2015;16:186–9.

    Article  Google Scholar 

  105. 105.

    Halsband C, Zapf A, Sixel-Doring F, Trenkwalder C, Mollenhauer B. The REM sleep behavior disorder screening questionnaire is not valid in de novo Parkinson’s disease. Mov Disord Clin Pract. 2018;5:171–6.

    Article  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Frauscher B, Mitterling T, Bode A, et al. A prospective questionnaire study in 100 healthy sleepers: non-bothersome forms of recognizable sleep disorders are still present. J Clin Sleep Med. 2014;10:623–9.

    Article  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Pujol M, Pujol J, Alonso T, et al. Idiopathic REM sleep behavior disorder in the elderly Spanish community: a primary care center study with a two-stage design using video-polysomnography. Sleep Med. 2017;40:116–21.

    Article  PubMed  PubMed Central  Google Scholar 

  108. 108.

    Sixel-Doring F, Trautmann E, Mollenhauer B, Trenkwalder C. Rapid eye movement sleep behavioral events: a new marker for neurodegeneration in early Parkinson disease? Sleep. 2014;37:431–8.

    Article  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Muntean ML, Trenkwalder C, Walters AS, Mollenhauer B, Sixel-Doring F. REM sleep behavioral events and dreaming. J Clin Sleep Med. 2015;11:537–41.

    Article  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Cipolli C, Bolzani R, Massetani R, Murri L, Muratorio A. Dream structure in Parkinson’s patients. J Nerv Ment Dis. 1992;180:516–23.

    Article  CAS  Google Scholar 

  111. 111.

    Borek LL, Kohn R, Friedman JH. Phenomenology of dreams in Parkinson’s disease. Mov Disord. 2007;22:198–202.

    Article  Google Scholar 

  112. 112.

    Chou KL, Moro-De-Casillas ML, Amick MM, Borek LL, Friedman JH. Testosterone not associated with violent dreams or REM sleep behavior disorder in men with Parkinson’s. Mov Disord. 2007;22:411–4.

    Article  Google Scholar 

  113. 113.

    Bugalho P, Paiva T. Dream features in the early stages of Parkinson’s disease. J Neural Transm. 2011;118:1613–9.

    Article  Google Scholar 

  114. 114.

    Valli K, Frauscher B, Gschliesser V, et al. Can observers link dream content to behaviours in rapid eye movement sleep behaviour disorder? A cross-sectional experimental pilot study. J Sleep Res. 2012;21:21–9.

    Article  Google Scholar 

  115. 115.

    Valli K, Frauscher B, Peltomaa T, Gschliesser V, Revonsuo A, Hogl B. Dreaming furiously? A sleep laboratory study on the dream content of people with Parkinson’s disease and with or without rapid eye movement sleep behavior disorder. Sleep Med. 2015;16:419–27.

    Article  Google Scholar 

  116. 116.

    Bateman DE, Levett K, Marsden CD. Sleep benefit in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1999;67:384–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Sherif E, Valko PO, Overeem S, Baumann CR. Sleep benefit in Parkinson’s disease is associated with short sleep times. Parkinsonism Relat Disorrd. 2014;20:116–8.

    Article  Google Scholar 

  118. 118.

    Van Gilst MM, van Mierlo P, Bloem BR, Overeem S. Quantitative motor performance and sleep benefit in Parkinson disease. Sleep. 2015;38:1567–73.

    Article  PubMed  PubMed Central  Google Scholar 

  119. 119.

    Van Gilst MM, Bloem RR, Overeem S. Prospective assessment of subjective sleep benefit in Parkinson’s disease. BMC Neurol. 2015;15:2.

    Article  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Lee W, Evans AH, Williams DR. Objective measurement and characterization of sleep benefit in Parkinson’s disease. Mov Disord Clin Pract. 2017;4:590–6.

    Article  PubMed  PubMed Central  Google Scholar 

  121. 121.

    Lee W, Evans A, Williams DR. Subjective perception of sleep benefit in Parkinson’s disease: valid or irrelevant? Parkinsonism Relat Disord. 2017;42:90–94.

    Article  Google Scholar 

  122. 122.

    Van Gilst MM, Cramer IC, Bloem BR, Overeem S, Faber MJ. A grounded theory study on the influence of sleep on Parkinson’s symptoms. BMC Res Notes. 2016;9:299.

    Article  PubMed  PubMed Central  Google Scholar 

  123. 123.

    Hogl B, Arnulf I, Comella C, et al. Scales to assess sleep impairment in Parkinson’s disease: critique and recommendations. Mov Disord. 2010;25:2704–16.

    Article  Google Scholar 

  124. 124.

    Hogl B, Wetter TC, Trenkwalder C. [Pathophysiology, clinical aspects and therapy of sleep disorders in Parkinson disease]. Nervenarzt. 2001;72:416–24.

    Article  CAS  Google Scholar 

  125. 125.

    Wetter TC, Collado-Seidel V, Pollmacher T, Yassouridis A, Trenkwalder C. Sleep and periodic leg movement patterns in drug-free patients with Parkinson’s disease and multiple system atrophy. Sleep. 2000;23:361–7.

    Article  CAS  Google Scholar 

  126. 126.

    American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. American Psychiatric Association; 2013.

  127. 127.

    Stefani A, Frauscher B, Högl B. Diagnosis of REM sleep behavior disorder. In: Schenck CH, Högl B, Videnovic A, editors. Rapid-eye-movement sleep behavior disorder. Springer; 2019.

  128. 128.

    Fernandez-Arcos A, Iranzo A, Serradell M, Gaig C, Santamaria J. The clinical phenotype of idiopathic rapid eye movement sleep behavior disorder at presentation: a study in 203 consecutive patients. Sleep. 2016;39:121–32.

    Article  PubMed  PubMed Central  Google Scholar 

  129. 129.

    Iranzo A, Santamaria J. Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. Sleep. 2005;28:203–6.

    Article  Google Scholar 

  130. 130.

    Gaig C, Iranzo A, Pujol M, Perez H, Santamaria J. Periodic limb movements during sleep mimicking REM sleep behavior disorder: a new form of periodic limb movement disorder. Sleep. 2017;40.

  131. 131.

    Trenkwalder C, Kohnen R, Högl B, et al. Parkinson’s Disease Sleep scale—validation of the revised version PDSS-2. Mov Disord. 2011;26:644–52.

    Article  Google Scholar 

  132. 132.

    Martinez-Martin P, Visser M, Rodriguez-Blazquez C, Marinus J, Chaudhuri KR, van Hilten JJ. SCOPA-sleep and PDSS: two scales for assessment of sleep disorder in Parkinson’s disease. Mov Disord. 2008;23:1681–8.

    Article  Google Scholar 

  133. 133.

    Stefani A, Heidbreder A, Brandauer E, et al. Screening for idiopathic REM sleep behavior disorder: usefulness of actigraphy. Sleep. 2018;41.

  134. 134.

    Nepozitek J, Dostalova S, Kemlink D, et al. Fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder. J Sleep Res. 2019:e12819.

  135. 135.

    Frauscher B, Iranzo A, Gaig C, et al. Normative EMG values during REM sleep for the diagnosis of REM sleep behavior disorder. Sleep. 2012;35:835–47.

    Article  PubMed  PubMed Central  Google Scholar 

  136. 136.

    Fernandez-Arcos A, Iranzo A, Serradell M, et al. Diagnostic value of isolated mentalis versus mentalis plus upper limb electromyography in idiopathic REM sleep behavior disorder patients eventually developing a neurodegenerative syndrome. Sleep. 2017;40.

  137. 137.

    Pierantozzi M, Placidi F, Liguori C, et al. Rotigotine may improve sleep architecture in Parkinson’s disease: a double-blind, randomized, placebo-controlled polysomnographic study. Sleep Med. 2016;21:140–4.

    Article  Google Scholar 

  138. 138.

    Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease—an evidence-based medicine review. Mov Disord. 2019;34:180–98.

    Article  PubMed  PubMed Central  Google Scholar 

  139. 139.

    Postuma RB, Anang J, Pelletier A, et al. Caffeine as symptomatic treatment for Parkinson disease (Cafe-PD): a randomized trial. Neurology. 2017;89:1795–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. 140.

    Postuma RB, Lang AE, Munhoz RP, et al. Caffeine for treatment of Parkinson disease: a randomized controlled trial. Neurology. 2012;79:651–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. 141.

    Neikrug AB, Liu L, Avanzino JA, et al. Continuous positive airway pressure improves sleep and daytime sleepiness in patients with Parkinson disease and sleep apnea. Sleep. 2014;37:177–85.

    Article  PubMed  PubMed Central  Google Scholar 

  142. 142.

    Videnovic A. Management of sleep disorders in Parkinson’s disease and multiple system atrophy. Mov Disord. 2017;32:659–68.

    Article  PubMed  PubMed Central  Google Scholar 

  143. 143.

    Rutten S, Vriend C, Smit JH, et al. Bright light therapy for depression in Parkinson disease: a randomized controlled trial. Neurology. 2019;92:e1145–e1156.

    Article  Google Scholar 

  144. 144.

    Videnovic A, Högl B. Toward disease modification trials in RBD: challenges and opportunities. In: Schenck CH, Högl B, Videnovic A, editors. Rapid-eye-movement sleep behavior disorder. Springer; 2019.

  145. 145.

    Garcia-Borreguero D, Silber MH, Winkelman JW, et al. Guidelines for the first-line treatment of restless legs syndrome/Willis–Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation. Sleep Med. 2016;21:1–11.

    Article  Google Scholar 

  146. 146.

    Winkelmann J, Allen RP, Högl B, et al. Treatment of restless legs syndrome: evidence-based review and implications for clinical practice (Revised 2017). Mov Disord. 2018;33:1077–91.

    Article  Google Scholar 

  147. 147.

    Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: treatment of restless legs syndrome in adults: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016;87:2585–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. 148.

    Allen RP, Picchietti DL, Auerbach M, et al. Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis–Ekbom disease in adults and children: an IRLSSG task force report. Sleep Med. 2018;41:27–44.

    Article  Google Scholar 

  149. 149.

    Schenck CH, Högl B, Videnovic A, editors. Rapid-eye-movement sleep behavior disorder. Springer; 2019.

  150. 150.

    Howell MJ, Arneson PA, Schenck CH. A novel therapy for REM sleep behavior disorder (RBD). J Clin Sleep Med. 2011;7:639–44A.

    Article  PubMed  PubMed Central  Google Scholar 

  151. 151.

    Wang Y, Yang Y, Wu H, Lan D, Chen Y, Zhao Z. Effects of rotigotine on REM sleep behavior disorder in Parkinson disease. J Clin Sleep Med. 2016;12:1403–9.

    Article  PubMed  PubMed Central  Google Scholar 

  152. 152.

    Di Giacopo R, Fasano A, Quaranta D, Della Marca G, Bove F, Bentivoglio AR. Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson’s disease. Mov Disord. 2012;27:559–61.

    Article  CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Ambra Stefani.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Stefani, A., Högl, B. Sleep in Parkinson’s disease. Neuropsychopharmacol. 45, 121–128 (2020).

Download citation

Further reading


Quick links