Restless leg syndrome (RLS) is a common sleep disorder found in patients with PD with a prevalence estimated to range from 8 to 24% [9, 97,98,99]. Wen MC, Chan LL, Tan LCS, Tan EK. Gilat M, Coeytaux Jackson A, Marshall NS, et al. Chaudhari KR, Pal S, DiMarco A, Whately-Smith C, Bridgman K, Mathew R, et al. The potential for injury to the patient and/or bed partner, however, should quickly prompt initiation of therapy to reduce this risk [70, 71]. Parkinsons Disease (PD) is a neurodegenerative disorder characterised by motor and non-motor features. Other studies have since evaluated the melatonin receptor agonist ramelteon, though results are mixed [83, 84]. Liebenthal J, Valerio J, Ruoff C, Mahowald M. A Case of Rapid Eye Movement Sleep Behavior Disorder in Parkinson Disease Treated With Sodium Oxybate. In addition, daytime sleepiness also appears to significantly improve in this population [157]. RBD can signal risk for synucleinopathies, a group of neurological conditions such as Parkinson's disease that involve the formation of clumps of alpha-synuclein protein in the brain. 2018;27(3):e12673. Parkinsonism Relat Disord. 2019;40(6):1151-1156. In this post-hoc analysis, 31/38 patients randomised (14 Nabilone, 17 placebo) had sleep disturbance at baseline as measured by components of two analogous scales (NMSS and MDS-UPDRS-D2) and were compared. The https:// ensures that you are connecting to the 2018;97(5):e9750. Sleep Med. exercise, exercise. A study of early and untreated PD showed that EDS may be related to disease progression and is independent of other sleep disorders, while others have shown that dopaminergic medication appears to increase EDS in a dose-dependent fashion [132,133,134, 136]. Degeneration of human photosensitive retinal ganglion cells may explain sleep and circadian rhythms disorders in Parkinsons disease. Circadian rhythm dysfunction can lead to an advanced or delayed onset of sleep in patients and create disruption of normal sleep and wake times. Arnaldi D, Antelmi E, St Louis EK, Postuma RB, Arnulf I. Idiopathic REM sleep behavior disorder and neurodegenerative risk: To tell or not to tell to the patient? Kick, punch or grab the air or their bed partner. Nevertheless, we recommend caution when using dopaminergic treatment for RLS in PD populations. In PD, disruption of the circadian rhythm can be due to a number of factors [6, 10]. This can lead to significant changes in sleep and wake times, often creating off-setting sleep schedules between patients and caretakers [6]. 2014;9(2):e89741. Melatonin is favored due to its favorable side effect profile, while addition of clonazepam can be considered in refractory cases. Oxford University Press is a department of the University of Oxford. Tohoku J Exp Med. Decreased sleep quality in Parkinsons patients is associated with higher anxiety and depression prevalence and severity, and correlates with pain intensity and quality. Another open-label study following 39 patients on clonazepam for more than 2years found that 67% had complete elimination of sleep-related injuries and potentially injurious behaviors to self and/or bed partners [76]. Zhang X, Sun X, Wang J, Tang L, Xie A. Sleep disturbances in Parkinson's disease with emphasis on rapid eye movement sleep behavior disorder. Sleep disruption, including REM-sleep behaviour disorder and circadian rhythm dysfunction, is a well-recognised prodromal aspect of PD, although other features such as restless leg syndrome and other physical factors may contribute. Treatment of insomnia due to mood disturbances in PD has recently focused on nonpharmacologic therapies for both issues given their interaction. Rotigotine Objectively Improves Sleep in Parkinsons Disease: An Open-Label Pilot Study with Actigraphic Recording. This paper describes the post-hoc analysis of the trial investigating the effects on sleep outcomes in those known to experience sleep problems at baseline. But after researchers administered a DORA medication twice during a 24-hour period, they noted that the medication not only helped the animals fall asleep faster and for longer, it also reduced levels of dream enactment that are a hallmark of RBD. 2019;34(2):180-198. Here, we review the treatment options for common sleep issues encountered in PD. Post-operatively, these patients were on a higher mean dopamine equivalent dose than those without RLS, suggesting DBS either unmasked RLS symptoms or that the development of RLS represented augmentation [130]. Inclusion in an NLM database does not imply endorsement of, or agreement with, 2010;19(4):591-6. Postuma RB, Adler CH, Dugger BN, et al. Funct Neurol. These studies use the International Restless Legs Syndrome Study Group rating scale (IRLS) to assess severity of symptoms, where 010 is mild, 1120 is moderate, 2130 is severe, and 3140 is very severe. One study evaluated nocturnal mobility in patients with PD by using an accelerometer and number of turnover movements in bed [17]. The .gov means its official. The treatment of nocturnal symptoms typically employs long-acting forms of antiparkinsonian medication to last through a night of sleep. Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset. 3). Impact of sleep-related symptoms on clinical motor subtypes and disability in Parkinsons disease: a multicentre cross-sectional study. Cite this: Potential New Treatment for REM Sleep Behavior Disorder-Medscape-May30,2023. 2008;15 Suppl 1:14-20. Search for other works by this author on: Department of Psychiatry, University Hospital Dr. One study evaluated the effect of istradefylline, a selective adenosine A2A receptor antagonist, in 21 patients with EDS in PD [147]. Diagnosis and subsequent treatment of OSA with CPAP in a patient with comorbid RBD is paramount to help reduce nocturnal behaviors [74]. Disclaimer. Inoue Y, Shimizu T, Hirata K, et al. Parkinson's disease; REM sleep behaviour disorder (RBD); insomnia; non-motor symptoms; restless legs syndrome (RLS); sleep. Heim B, Djamshidian A, Heidbreder A, et al. Exclusion criteria of note included those with significant cerebral parenchymal or cerebrovascular abnormalities, very low cognitive scores, and subjects with poor-quality imaging. JAMA Neurol. Careers, Unable to load your collection due to an error. For those younger than 40, antidepressants are the most common cause of REM sleep behavior disorder; in these younger patients, it affects biological males and females about equally, but past age 50, it's more common in biological males. For most neurodegenerative disorders, there is a phase that may last for decades in which brain changes are taking place but the patient either remains asymptomatic or develops symptoms without the full expression of the disease. FOIA Motor and nonmotor features that lead to insomnia often require pharmacologic adjustment for treatment, though CBT can be effective in mood disorders that lead to insomnia. Evaluation and treatment of comorbid conditions such as prostate hypertrophy may also be helpful in reducing urinary symptoms [33]. BMJ. Sleep and Circadian Rhythm Disorders in Parkinsons Disease. Long-term effects of bilateral subthalamic nucleus stimulation on sleep in patients with Parkinsons disease. Jazz Pharma Ruling Clears USRoadblock for Rival Narcolepsy Drug, Improved Screening for Post-op Delirium Holds Promise, NICE Publishes Delayed ME/CFS Guidance After Summer Controversy, Vanda Pharmaceuticals Sues USGovernment Over Drug Trade Secrets, Disordered Sleep Tied to a Marked Increase in Stroke Risk. In a long-term study of 1,280 patients with REM sleep behavior disorder who didn't have parkinsonisman umbrella term that refers to brain conditions, including Parkinson's disease, that cause slowed movements, stiffness and tremorsor dementia, researchers followed participants to find out how many would develop these disorders. Ozawa M, Murakami H, Shiraishi T, Umehara T, Omoto S, Iguchi Y. Acta Neurol Belg. Published online May 25, 2203. 2019;266(3):636-641. Observational Study of the Relation between Parkinsons Disease and Sleep Apnea. In a large placebo-controlled trial, pregabalin was compared to two doses of pramipexole (0.25mg and 0.5mg) over 12weeks and found to be effective at reducing RLS severity compared to baseline [128]. These behaviors during sleep may range from mild muscle twitches to vocalizations to violent and complex motor behaviors. Drug Des Devel Ther. Symptoms are worse in the evening or at night than during the day or only occur in the evening or night. Comment: The novel application of this emerging technology, together with issues in cohort matching, limits applicability. Ann Intern Med. And the Epworth Scale helped us identify 33 patients (50%) with a possible pathological excessive daytime sleepiness, none of them diagnosed. Boeve BF. Sleep and circadian rhythm regulation in early Parkinson disease. JAMA Neurol. Other chronotherapies including physical exercise and melatonin may be beneficial but have not been systematically evaluated in patients with PD. Neurol Res. The study was funded by the Alzheimers Association and Merck Investigator Studies Program. As this has not been studied in PD populations, use of opiates should be considered with extreme caution, if not avoided altogether due to risk of sedation and respiratory depression. Aside from these clinical issues of sleep disorders in PD, the concept of REM-sleep behaviour disorder (RBD) as an early sign for emerging neurodegenerative diseases is of pivotal interest for future research on biomarkers and neuroprotective treatment strategies of neurodegenerative diseases, and particularly PD. PubMed [9], Although treatment strategies essentially remain the same for RLS and PLMD in PD as in other patients, with dopamine agonists and Levodopa, the main challenge often is to control symptoms, when patients are already on high doses of these agents for PD. https://doi.org/10.1007/s13311-020-00938-y, DOI: https://doi.org/10.1007/s13311-020-00938-y. Saper CB. Gabapentin acts via binding at the alpha-2-delta subunit of the voltage-gated calcium channel, which reduces release of excitatory neurotransmitters, including glutamate [119, 120, 126]. - 85.214.80.177. 29.7% of patients in the Nabilone group worsened by at least one point on the MDS-UPDRS suggesting a wearing-off effect may occur and a longer follow-up would be useful to explore this. Sleep Med Clin. Article PLoS One. (REM) sleep behavior disorder (RBD) confirmed by video-polysomnography. Hurt CS, Rixon L, Chaudhuri KR, Moss-Morris R, Samuel M, Brown RG. J Neurol. Di Giacopo R, Fasano A, Quaranta D, Della Marca G, Bove F, Bentivoglio AR. Injuries often result from these incidents; patients may fall from bed or accidentally harm a partner. Mov Disord. Rapid eye movement sleep behavior disorder is associated with decreased quality of life and stigma in people with Parkinson's disease. This can manifest as pathologic gambling, impulsive shopping, sexual behaviors, and eating. You've successfully added to your alerts. The NMS Questionnaire is a 30-item comprehensive questionnaire that assesses multiple motor and nonmotor domains, including sleep dysfunction [14]. The rationale for acetylcholinesterase inhibitors is based on empiric evidence that the presence of RBD in PD is associated with cholinergic denervation [85]. Primary and secondary features of Parkinsons disease improve with strategic exposure to bright light: a case series study. 2018;22(3):825-830. Drug treatment of REM sleep behavior disorders in dementia with Lewy bodies. This double-blind, placebo-controlled study was undertaken in a single centre in Austria. Can Asthma Incidence Be Reduced by Attention to Sleep Disorders? Treatment flow chart for insomnia in Parkinsons disease (PD). Please confirm that you would like to log out of Medscape. Mov Disord. Your comment will be reviewed and published at the journal's discretion. Appropriate testing, including a sleep study, are needed to determine if a patient has REM sleep behavior disorder, as opposed to another disorder, such as obstructive sleep apnea. Read the original article. Although we suggest alpha-2-delta ligand agents as first-line therapy for treatment of RLS in PD as monotherapy or in combination with other agents, dopaminergic medications are also effective for treatment of both RLS and motor symptoms of PD. Sleep Med. All other doses up to 2400mg were also effective at reducing RLS severity (p<0.01). In phase 2, patients were randomised to continue on their optimal dose or placebo for 4weeks. However, the only RCT using clonazepam in patients with RBD and PD failed to show superiority over placebo. Istradefylline improves daytime sleepiness in patients with Parkinsons disease: An open-label, 3-month study. Parkinsonism Relat Disord. As a library, NLM provides access to scientific literature. Ann Neurol. Routine testing of this protein in cerebrospinal fluid (CSF) is not currently established as a useful or necessary biomarker for diagnosis or monitoring of disease progression. Sleep. Improved understanding of central causes may be key to developing novel, effective and targeted treatments. Claassen DO, Josephs KA, Ahlskog JE. 2012; 19(1):105-13. In cases where oral supplementation is not tolerated or a rapid response is needed, infusions of 1g of iron dextran or ferrous carboxymaltose in two separate doses 1week apart can be beneficial. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. 2016; 33:51-57. Randomized, Controlled Trial of Exercise on Objective and Subjective Sleep in Parkinsons Disease. Butala A, Shepard M, Pontone G. Neuropsychiatric aspects of Parkinson disease psychopharmacology: Insights from circuit dynamics. Sleep. sharing sensitive information, make sure youre on a federal A definitive diagnosis requires polysomnography (PSG) confirmation of abnormal tonic elevation and/or bursts of muscle tone measured by electromyography (EMG), termed loss of REM atonia [60]. REM sleep behaviour disorder is associated with worse quality of life and other non-motor features in early Parkinsons disease. 2017;12(11):e0187616. This site needs JavaScript to work properly. 2005;76(12):1636-9. Parkinson's / Movement Disorders; Sleep Medicine; Stroke; VA Hospital Neurology; Supplemental Faculty; . Sleep disturbance in patients with Parkinson's disease (PD) is highly prevalent. Neurology. Front Neurol. This is a disorder in which breathing is interrupted during sleep. The site is secure. J Strength Cond Res. Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips, Not logged in Handb Clin Neurol. However, most strategies employ use of long-acting medications to last throughout the night [18]. PD is associated with multiple sleep disorders, which commonly impair quality of life. Sleep disturbances are one of the most common of the nonmotor complications of Parkinson's disease (PD), and increase in frequency with advancing disease. De Cock Cochen V. Therapies for Restless Legs in Parkinsons Disease. 2017 1;40(2). Videnovic A, Noble C, Reid KJ, et al. 2009;32(3):158-9. 2016;165(2):125-33. 2012;71(4):560-8. A diagnosis of probable RBD can be made clinically based on the presence of nocturnal behaviors associated with vivid or violent dreams [60]. Nabilone demonstrated a positive short-term response in a majority of a small cohort of patients with PD and may prove a promising option in select patients. The Epworth Sleepiness Scale (ESS) is a 24-point scale used to identify individuals with sleepiness, with a score of greater than 10 indicating excessive daytime sleepiness. 21 (2016) 114120. Bethesda, MD 20894, Web Policies Every night, you go through four to five sleep cycles. The choice of therapy for RLS in PD should be tailored to the individual patient with an understanding that problematic side effects from long-term dopamine agonist use can occur. The main factors responsible for disturbed sleep in PD have been classified by Barone et al, into the following four subcategories: [ 5] 1) PD-related motor symptoms, including nocturnal akinesia, early-morning dystonia, painful cramps, tremor and difficulty turning in bed; 2) treatment-related nocturnal disturbances with drugs like levodopa, ot. 2007;24(3):521-37. Epub 2023 Mar 21. Larsen JP, Tandberg E. Sleep disorders in patients with Parkinson's disease: Epidemiology and management. 2015;63(11):2227-46. [7] [Table 1], Approach to sleep-related problems in patients with PD, RLS is diagnosed by specific criteria laid down by the international RLS study group:[8], The diagnosis of PLMD can be suspected clinically, typically with the bed partner complaining of jerky limb movements occurring periodically every few seconds or minutes. This study focusses on the relationship between sleep disorders and alpha-synuclein levels in CSF, comparing individuals with established PD, prodromal PD, and healthy controls. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Deli G, Aschermann Z, cs P, et al. Slider with three articles shown per slide. Motor symptoms from PD such as tremor, dystonia, and rigidity can contribute to insomnia. The following table summarizes a brief approach toward diagnosis and management of sleep disorders: National Library of Medicine 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. Because of the negative impact that EDS has on quality of life in PD, identification and treatment is important. NPJ Parkinsons Dis. Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase III Randomized Controlled Clinical Trials. Zuzurregui, J.R.P., During, E.H. Sleep Issues in Parkinsons Disease and Their Management. First-line therapies for RBD include an assessment of bedroom safety, followed by melatonin and clonazepam. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Winkelman JW, Armstrong MJ, Allen RP, et al. 2007; 6(6):513-20. Dopaminergic medications may also negatively impact the circadian rhythm by reducing melatonin secretion, which rises during the early evening hours preceding sleep in healthy subjects [6, 10, 162]. In addition, doses of clonazepam higher than 0.5mg may be more effective based on observational studies and anecdotal evidence. If you suspect you have REM sleep behavior disorder, see a sleep specialist or neurologist. Various exercise programs have been shown to be helpful in improving sleep. This 4-week trial in 40 patients with probable RBD treated with fixed 0.5-mg dose of clonazepam or placebo showed no difference between groups based on the Clinical Global Impressions-Improvement (CGI-I) scores [77]. The diagnosis of RLS requires four criteria: (1) the urge to move ones extremities due to severe discomfort or pain (a subset of patients may also experience symptoms in their arms or back); (2) the urge starts or worsens during periods of rest; (3) the urge can occur throughout the day but is worse during the evening or night; (4) the urge is decreased or relieved by movement [97]. Simuni T, Caspell-Garcia C, Coffey C, et al. 2014;370(7):621-31. The presence of poor sleep and mood disturbances appears to have a reciprocal relationship, with the presence of one appearing to worsen the other [40,41,42]. In recent years, significant efforts have been undertaken to identify biomarkers in biological fluids. Unable to load your collection due to an error, Unable to load your delegates due to an error. Google Scholar. PubMed Central Your email address is used only to let the recipient know who sent the email. Clinical usefulness of the Parkinson's disease sleep scale. Scholz H, Trenkwalder C, Kohnen R, Riemann D, Kriston L, Hornyak M. Levodopa for restless legs syndrome. Iranzo A, Fernndez-Arcos A, Tolosa E, et al. Neurology. Happe S, Ludemann P, Berger K. The association between disease severity and sleep-related problems in patients with Parkinson's disease. Nearly a third of the older animals showed behaviors similar to REM sleep behavior disorder in humans, including chewing and limb extension. Hu X, Li J, Wang X, Liu H, Wang T, Lin Z, Xiong N. Antioxidants (Basel). However, a larger follow-up study (n=40) did not find that modafinil up to 400mg significantly reduced ESS, though a mean reduction in ESS of 2.7 was seen after 4weeks of treatment [145]. 2011;310(1-2):286-8. Bookshelf Immobility in bed due to hypokinesia from PD has also been associated with an increased wake after sleep onset [16]. It did suggest that alteration of the laryngopharyngeal motor control may be a distinct mechanism contributing to OSA in PD. government site. Improvements in nocturnal symptoms with ropinirole prolonged release in patients with advanced Parkinsons disease. Scaglione C, Vignatelli L, Plazzi G, Marchese R, Negrotti A, Rizzo G, et al. Sleep Issues in Parkinsons Disease and Their Management, https://doi.org/10.1007/s13311-020-00938-y, rapid eye movement sleep behavior disorder (RBD), New awakenings: current understanding of sleep dysfunction and its treatment in Parkinsons disease, Longitudinal Studies of Sleep Disturbances in Parkinsons Disease, Sleep Dysfunction in Movement Disorders: a Window to the Disease Biology, Effects of melatonin prolonged-release on both sleep and motor symptoms in Parkinsons disease: a preliminary evidence, Progression of sleep disturbances in Parkinsons disease: a 5-year longitudinal study, Sleepwake and circadian disturbances in Parkinson disease: a short clinical guide, Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder, A Case-Based Approach to the Identification and Treatment of Sleep Disorders in Neurology Practice, Polysomnographic Predictors of Sleep, Motor, and Cognitive Dysfunction Progression in Parkinsons Disease. Another trial (n=61) evaluated the use of caffeine in patients with EDS in PD [142]. J Sleep Res. An official website of the United States government. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Studies have shown that sleep apnea is not commoner in patients with PD than in the general population. A guideline for the management of bladder dysfunction in Parkinsons disease and other gait disorders. Chronic use of benzodiazepine and benzodiazepine receptor agonists may lead to cognitive decline and dementia in non-PD populations [54]. FOIA This corroborated an earlier study which demonstrated the same difference in IRLS scores after 12weeks of treatment with pramipexole compared to placebo [114]. Anti-parkinsonian medication was temporarily withheld prior to the MRI where relevant, though the effect of this on results is unclear. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease. 2015;32(7):559-67. Int J Neurosci. Zeng J, Wei M, Li T, et al. Harmell AL, Neikrug AB, Palmer BW, et al. There was no known correlation between RBD and abnormal accumulation of tau. Non-motor symptoms of Parkinson's disease (PD) such as dysautonomia and REM sleep behavior disorder (RBD) are recognized to be important prodromal symptoms that may also indicate clinical . Multiple RCTs have evaluated the use of the stimulant modafinil for EDS in PD with mixed results. Similarly, a long-acting form of ropinirole and immediate-release pramipexole have both been shown to significantly improve overall PDSS scores when added as adjunctive therapy to levodopa in patients with significant sleep difficulties at night [22, 23]. Sleep Med 2013;14:67584. However, limited evidence in a cognitively impaired population suggests it does not worsen cognition and may be used safely in these groups [36]. Doxepin and cognitive behavioural therapy for insomnia in patients with Parkinsons disease -- a randomized study. Nat Rev Neurol. Get news updates direct to your inbox by signing up to our daily newsletter here, The disorder is most common in men in their 40s and 50s and affects approximately 1% of the general population, Irish Mirror - Irish Mirror News - Daily news updates. Google Scholar. Curr Treat Options Neurol. Opiates have also been shown to be effective for reducing RLS severity, but are generally reserved for those who have failed other agents or augmentation that has been reticent to other therapies [111, 119, 126, 129]. The Conversation talked with Anelyssa D'Abreu, a neurologist who specializes in geriatric neurology, to explain what researchers know about the condition's links to dementia. 2016;73(1):126-7. A double-blind RCT found that IRLS scores were significantly lower on a 2-mg or 3-mg rotigotine patch compared to placebo after 6months of treatment (p<0.001) [115]. After 12 years, 73.5% of those with REM sleep behavior disorder had developed a related neurodegenerative disorder. Peyronnet B, Vurture G, Palma JA, et al. HHS Vulnerability Disclosure, Help However, most antidepressants with the exception of bupropion can exacerbate rapid eye movement sleep behavior disorder and restless legs syndrome, both common in patients with PD [52, 53]. 2018;40(8):696-701. Alpha-2-delta ligand agents (pregabalin, gabapentin, and gabapentin enacarbil) are now considered first-line therapy and are effective in reducing RLS symptoms [102, 109, 111, 119, 120]. Freezing of gait (FOG) in Parkinson's disease (PD) is a common and disabling symptom characterized by sudden, paroxysmal motor arrest during walking that often leads to falls and poor quality of life. Nabilone was given as an escalating dose regime up to a maximum of 2mg, until NMS were much improved on the Clinical Global Impression of Improvement (CGI-I) scale. Please use this form to submit your questions or comments on how to make this article more useful to clinicians. Am J Geriatr Psychiatry. Medical Advisory Board of the Willis-Ekbom Disease Foundation. Treatment should focus on the underlying issue, with most patients requiring multiple treatment modalities depending on the stage of disease (Fig. This article has been reviewed according to ScienceX's Cell Tissue Res. Subjectively impaired bed mobility in Parkinson disease affects sleep efficiency. REM sleep behaviour disorder has been linked with Parkinsons disease and dementia with Lewy bodies, a long-term study showed. J Neurosci. Selection of the specific medication used should be individualized to the patient, though it appears that most long-acting oral and transdermal medications for PD are effective in reducing motor symptoms that disrupt sleep. 2013; 14(7):668-74. Course and risk factors for excessive daytime sleepiness in Parkinsons disease. One study evaluated a cohort of 412 patients with PD, 209 of whom (51%) had trouble with initiation of sleep or fragmentation during the 5-year study [11]. Many studies have used this as primary endpoint to evaluate changes in daytime sleepiness. Neurology. (2022), npj Parkinson's Disease, 8(1) 19. Giorgi L, Asgharian A, Hunter B. Ropinirole in patients with restless legs syndrome and baseline IRLS total scores 24: efficacy and tolerability in a 26-week, double-blind, parallel-group, placebo-controlled study followed by a 40-week open-label extension. Timed Light Therapy for Sleep and Daytime Sleepiness Associated With Parkinson Disease: A Randomized Clinical Trial. Schenck CH, Mahowald MW. (2022), Journal of Neurology, 269(5) 24692478. 8600 Rockville Pike A trial to investigate use of this medication in patients with RBD is currently underway (NCT04006925). Brain Behav. For reasons that are poorly understood, the dream content is usually violentpatients report being chased, or defending themselves, and as they sleep they shout, moan, scream, kick, punch and thrash about. Interestingly, there was clinically significant improvement of RLS symptoms with placebo in many of the above trials which highlights the suggestibility of this disorder. Interestingly, patients with PD and EDS appeared to have reduced uptake in the basal ganglia on dopaminergic terminal imaging compared to those without EDS [133, 139]. Researchers used an animal model for the study, which they say is the first to identify a new form of treatment for RBD. 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. Management of sleep disorders in PD patients usually starts with optimization of (dopaminergic) antiparkinsonian therapy followed by specific treatment of the sleep disturbances. One controlled study demonstrated that subjective sleep quality improved in patients with PD after participation in a 12-week resistance training program compared to non-exercisers [49]. Efficacy of pramipexole and transdermal rotigotine in advanced Parkinsons disease: a double-blind, double-dummy, randomised controlled trial. Nevertheless, adherence to CPAP in patients with PD and OSA should be addressed and may help with daytime sleepiness, as well as reduce the risk of other medical comorbidities. That fourth stage is REM sleep. Parkinsonism Relat Disord. Alteration of the circadian rhythm is common in PD. An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder. 2011;(2):CD005504. the contents by NLM or the National Institutes of Health. J Clin Sleep Med. This would suggest that sleep dysfunction due to motor symptoms is not as prominent early in or with a less severe disease state. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. In a long-term study of 1,280 patients with REM sleep behavior disorder who didn't have parkinsonism - an umbrella term that refers to brain conditions, including Parkinson's disease, that cause slowed movements, stiffness, and tremors - or dementia, researchers followed participants to find out how many would develop these disorders.. After 12 years, 73.5 percent of those with REM sleep . Prevalence and profile of Restless Legs Syndrome in Parkinsons disease and other neurodegenerative disorders: a case-control study. In a long-term study of 1,280 patients with REM sleep behavior disorder who didn't have parkinsonism - an umbrella term that refers to brain conditions, including Parkinson's disease, that . In a long-term study of 1,280 patients with REM sleep behavior disorder who didn't have parkinsonisman umbrella term that refers to brain conditions, including Parkinson's disease, that cause . The Clinical Phenotype of Idiopathic Rapid Eye Movement Sleep Behavior Disorder at Presentation: A Study in 203 Consecutive Patients. Patients who are affected by REM sleep behavior disorder may choose to participate in research. Sharma VD, Sengupta S, Chitnis S, Amara AW. 2013;14(1):24-9. Adler CH, Caviness JN, Hentz JG, Lind M, Tiede J. Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinsons disease. RBD may be detectable decades before the symptoms develops full. 2002;25(8):905-9. Insomnia is defined as difficulty with initiating sleep, maintaining sleep and awakening earlier than desired for at least 3days per week over 3months [10]. 2009;10(1):60-5. This often leads to an increase in dopaminergic medications, triggering further augmentation. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Parkinsonism Relat Disord. Epub 2012 May 11. Secondly, we explore the role of Diffusion Tensor Imaging in assessing the glymphatic system in a similar cohort comparison. Conditions associated with REM sleep behaviour disorder: Description of a hospital series. Clinically relevant cut-off values for the Parkinsons Disease Sleep Scale-2 (PDSS-2): a validation study. J Clin Mov Disord. National Library of Medicine There is increasing interest in the effects of sleep and sleep disturbances on the brain, particularly in relation to aging and neurodegenerative processes. We review the literature regarding these common sleep issues encountered in PD and their treatment options. Mery VP, Gros P, Lafontaine AL, Robinson A, Benedetti A, Kimoff RJ, Kaminska M. Reduced cognitive function in patients with Parkinson disease and obstructive sleep apnea. Zhu K, van Hilten JJ, Marinus J. People with the disorder act out their dreams by talking, flailing their arms and legs . The test, called IP/RT-QuIC, detects early-formed alpha-synuclein fibrils, study finds. 2003;15(4):377-83. Bright light therapy administered in the morning has been evaluated in a small sample size and was not shown to be beneficial in patients with PD, anxiety, and insomnia [48]. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, Chaudhuri KR, Group NV. Total sleep time in patients with PD appeared to have a greater correlation with depression severity than that in controls which could reflect a synergistic effect of depression and PD on sleep duration (p<0.05) [43]. government site. Neurostimulation for Parkinsons disease with early motor complications. Called REM sleep . Factors contributing to the development of restless legs syndrome in patients with Parkinson disease. Continuum (Minneap Minn). The Parkinsons disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinsons disease.J Neurol Neurosurg Psychiatry. Neurology. Bilateral Subthalamic Stimulation can Improve Sleep Quality in Parkinsons Disease. 2019;119(4):607-613. Kurcova S, Bardon J, Vastik M, et al. Sleep disturbance was measured by the REM-sleep Behaviour Disorder Screening Questionnaire (RBDSQ) and Epworth Sleepiness Scale (ESS). Using the PSQI we identified 56 patients (86.1%) with low-quality sleep (defined as a score of 5 or higher). Irregular motor symptoms, abnormal dopamine levels, loss of sense of smell, cognitive impairment, abnormal colour vision, erectile dysfunction, constipation in older age, were also associated with the sleep behaviour disorder. the following attributes while ensuring the content's credibility: by Anelyssa D'Abreu, The Conversation. editorial process It is observed in 25% to 58% of patients diagnosed with Parkinson's, 70% to 80% of . Treatment, as in all patients with obstructive sleep apnea, is with continuous positive airway pressure (CPAP). Comorbidities, treatment, and pathophysiology in restless legs syndrome. Apart from any fair dealing for the purpose of private study or research, no This data on augmentation has only been studied in non-PD RLS populations, however, limiting applicability to the PD population with RLS. Kumru H, Iranzo A, Carrasco E, et al. Would you like email updates of new search results? Melatonin is preferred given a lower side effect profile. On the one hand regulation of sleep and wakefulness is affected in. Rotigotine may improve sleep architecture in Parkinsons disease: a double-blind, randomized, placebo-controlled polysomnographic study. Curr Sleep Med Rep. 2017 Sep;3(3):222-234. REM sleep behavior disorder may also be observed in other neurodegenerative disorders such as Alzheimer's disease and Huntington's disease, but at much lower rates. REM sleep behavior disorder may be the first symptom of Parkinson's disease or dementia with Lewy bodies. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. *Suggested first-line therapies. People with the disorder act out their dreams by talking, flailing their arms and legs, punching, kicking and exhibiting other behaviors while asleep. Kay DB, Tanner JJ, Bowers D. Sleep disturbances and depression severity in patients with Parkinsons disease. For those with insomnia and comorbid mood disorders, nonpharmacologic interventions such as CBT and exercise appear to have significant benefit on subjective and objective sleep. Thank you for submitting a comment on this article. Louter M, van Sloun RJ, Pevernagie DA, et al. Mov Disord 2010;25:16751683. While virtually anyone could be at risk for developing Parkinson's, some research studies suggest this disease . Sleep disorders are among the most common nonmotor symptoms in Parkinson's disease and are associated with reduced cognition and health-related quality of life. No correlation was found between RLS severity and reduction in PD medications, suggesting that STN DBS may have mediated this improvement [131]. government site. 2020;35(6):947-958. International Classification of Sleep Disorders, Revised: Diagnostic and Coding Manual. Parkinsonism Relat Disord. The medication was well tolerated with side effects consistent with its known profile. Mov Disord. Longitudinal assessment of excessive daytime sleepiness in early Parkinsons disease. 2012; 18(1):54-8. By using our site, you acknowledge that you have read and understand our Privacy Policy Eur J Neurol. Gabapentin enacarbil, a prodrug and controlled-release form of gabapentin, has since been shown to be superior to placebo for reduction of RLS symptoms in multiple double-blind RCTs [111]. A total of 65 patients (26 females, 39 males) that attended the outpatient Parkinsons clinic were screened for sleep disorders. J Parkinsons Dis. If ferritin levels are <75ng/ml and/or transferrin saturation index <20%, oral ferrous sulfate 325mg with vitamin C has been recommended [108, 109]. 1). Recently, a fifth criteria was added to state that the above features should not be solely accounted for by another medical or behavioral condition, such as myalgias or leg cramps [97]. Finally, sodium oxybate has been used when other therapies failed, with some success in four case reports of patients with and without PD [94,95,96]. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Parkinsonism Relat Disord. A little-known and poorly understood sleep disorder that occurs during the rapid eye movement, or REM, stage of sleep has been garnering attention for its role in foreshadowing neurodegenerative brain diseases such as Parkinson's disease and dementia with Lewy bodies. Rios Romenets S, Creti L, Fichten C, et al. Although early research suggested that decreases in dopamine and norepinephrine were involved in the development of depression in PD, recent literature suggests that serotonin plays a more prominent role [38, 39]. "The bigger highlight here is less about what's causing the RBD as to what you can do to make it better," he said. PubMedGoogle Scholar. 2018;12:2017-2024. A limitation of this study is the length of follow-up, as it may take longer treatment with CPAP to produce improvement in cognition. About 3 million people in the United States have RBD, which is often a precursor to Parkinson's disease. Notable restoration of atonia during REM on PSG was also demonstrated in a similar study [80]. Gabryelska A, Roguski A, Simpson G, Maschauer EL, Morrison I, Riha RL. 2017;38(1):163-170. de Gage Billioti S, Moride Y, Ducruet T, et al. 2014;37(2):369-72. Second-line treatments could include rivastigmine, donepezil, dopaminergic agents, or sodium oxybate in more severe cases (Fig. If the above measures have not provided sufficient relief, pharmacologic management is recommended. Sleep 1999;22:10731081. 2011;26(4):644-52. Neuropsychiatr Dis Treat. Emergence of restless legs syndrome after subthalamic stimulation in Parkinsons disease: a dopaminergic overstimulation? 2014;349:g5205. In China, approximately 48-89% of Chinese patients with PD have been shown to be affected by sleep disorders. The test, called immunoprecipitation-based real-time quaking . Willis GL, Turner EJ. EDS in PD can be multifactorial. PubMed Central "We're using something completely different, which raises the possibility this might be something useful for REM behavior disorders.". Sleep Med. Patients of the outpatient clinic whom their medical query wasnt about sleeping disorder were screened using the following clinical tools: the Pittsburgh Sleep Quality Index (PSQI), the Patient Health Questionnaire (PHQ-9), the STOP-BANG Questionnaire, and the Epworth Scale. This suggests that more severe disease could be a contributing factor to development of EDS, in addition to dopamine medication levels [133, 135]. 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. Inclusion in an NLM database does not imply endorsement of, or agreement with, Garca-Borreguero D. Dopaminergic Augmentation in Restless Legs Syndrome/Willis-Ekbom Disease: Identification and Management. 2013;8(12):e82091. Ropinirole was compared to placebo in patients with at least severe RLS (40-point International restless legs scale score>24; IRLS). This stage is often accompanied by muscle twitches and fluctuations in your respiratory rate and blood pressure. Jos Rafael P. Zuzurregui. However, a more recent case-control study (n=3194) evaluated 194 patients with PD with PSG and found significantly higher rates of OSA compared to controls (p<0.05) [149]. This aberrant process may result in alpha-synuclein accumulation and have relevance for disease progression. Medications used for treatment of motor and nonmotor symptoms in PD can also worsen RLS. Dhawan V, Healy DG, Pal S, Chaudhuri KR. [Sleep disturbances in Parkinson's disease: characteristics, evaluation and therapeutic approaches]. Google Scholar. Romenets SR, Wolfson C, Galatas C, et al. The latter will be discussed later in this review. One study evaluated 98 patients with and without PD using the Insomnia Severity Index (ISI) and Beck Depression Inventory to measure the impact of insomnia on depression [43]. Int J Geriatr Psychiatry. Esaki Y, Kitajima T, Koike S, et al. 14 Citations 14 Altmetric Metrics Abstract Alpha-synucleinopathy is postulated to be central to both idiopathic rapid eye movement sleep behaviour disorder (iRBD) and Parkinson's disease. 2017;32:16-21. 2014;85(5):560-6. Treatment of nocturia may focus initially on behavioral interventions, such as reduction of fluid intake in the evening and adjustment of diuretic agents to the morning. However, there were no significant differences in either the composite or 13 individual neuropsychological tests in both groups [158]. 2017;136(2):84-96. One prospective study evaluated 31 PD patients with STN DBS who did not have RLS at baseline [130]. 2018;387:220-227. N Engl J Med. 2018;131(8):899-906. The effect of diet-induced obesity on sleep and breathing in female mice, The Mystery of GHB Efficacy in Narcolepsy Type 1, Comparison of sleep parameters from wrist-worn ActiGraph and Actiwatch devices, Change of iron content in brain regions after intravenous iron therapy in restless legs syndrome: quantitative susceptibility mapping study, Opportunities for Patient-Centered Sleep Research, Cognitive, Affective and Behavioral Neuroscience of Sleep, https://doi.org/10.1093/sleep/zsad077.0877, https://academic.oup.com/pages/standard-publication-reuse-rights, Receive exclusive offers and updates from Oxford Academic, MEDICAL MICROBIOLOGY AND CLINICAL LABORATORY MEDICINE PHYSICIAN, CLINICAL CHEMISTRY LABORATORY MEDICINE PHYSICIAN. Men over 50 are affected more than women of the same age. BID? Treatment of RLS in PD should begin with nonpharmacologic measures, but often requires use of medication due to severity of symptoms (Fig. [3] The following sleep-related issues are included in this scale: This, along with the widely accepted sleepiness scale, the Epworth Sleepiness Scale is an easy to apply instrument for identifying sleep-related problems in PD. Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder. Parkinson disease (PD) is a neurodegenerative disorder first described by James Parkinson in his ' Essay on Shaking Palsy' 1. Interestingly, significant improvement of REM atonia was seen on PSG in the melatonin group (p=0.012) [79], which was sustained for several weeks. 2017;88(11):953-959. Gatto EM, Aldinio V. Impulse Control Disorders in Parkinsons Disease. JAMA Neurol. Caffeine for treatment of Parkinson disease: a randomized controlled trial. Santiago PL, Rossi M, Cardinali DP, Merello M. Activity-rest rhythm abnormalities in Parkinson's disease patients are related to dopaminergic therapy. Second-line agents include dopaminergic medications commonly used for treatment of PD, but should be used with caution. In healthy individuals, this rhythm allows for the alternance of sleep and wake as continuous, prolonged, and well-demarcated phases that align with an individuals social and/or professional demands, as well as preference [6, 10]. Other sleep disorders that may contribute to hypersomnia should also be ruled out and treated. Effect of pramipexole on RLS symptoms and sleep: a randomized, double-blind, placebo-controlled trial. Sleep Disorders Related to Parkinson's Disease In addition to other sleep problems, people with Parkinson's disease appear to be more susceptible to certain sleep conditions: Circadian rhythm disruptions: Reduced dopamine may significantly alter the body's sleep-wake cycle The most common of these neurodegenerative disorders is Parkinson's disease. In keeping with previous research, CSF alpha-synuclein at baseline was lowest in the PD group, followed by the prodromal PD group, and then the control group. [6] In addition, for specific assessment for RBD, the RBD clinical questionnaire can be used. The monoamine oxidase B inhibitor rasagiline was also evaluated using the PDSS and was shown to improve nocturnal tremor and restlessness in patients with PD [25]. Google Scholar. About 3 million people in the United States have RBD, which is often a precursor to Parkinson's disease. 2018;17(11):994-1005. This article is republished from The Conversation under a Creative Commons license. REM sleep behavior disorder and neuropathology in Parkinsons disease. Some of the factors that independently increased the risk of developing a neurodegenerative disorder were the presence of irregular motor symptoms, abnormal dopamine levels, loss of sense of smell, cognitive impairment, abnormal color vision, erectile dysfunction, constipation and older age. Other medications such as bupropion and dextroamphetamine have been suggested as possible treatments; however, there are no published data evaluating these agents [148]. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: A descriptive study. Individual questions include tremor, immobility in bed, and dystonia, as well as nocturia and hallucinations. In limited studies of this technology to date, higher ALPS scores have been associated with an improved glymphatic activity. More recently, clonazepam has been evaluated in a prospective fashion. Although some studies suggest that RLS may be an early neurological symptom in PD, others have found that RLS incidence is not increased before initiation of PD treatment [104,105,106,107]. A highly sensitive blood test accurately identified people with synucleinopathies, disorders caused by the abnormal aggregation of the protein alpha-synuclein, such as Parkinson's disease. Introduction. Dose response of Gabapentin Enacarbil versus placebo in subjects with moderate-to-severe primary restless legs syndrome: an integrated analysis of three 12-week studies. Interestingly, the ESS remained with a nearly 4-point improvement after intervention and 2-week washout period in the PD group, as well as a 2-point improvement sustained in the control group, suggesting a prolonged effect of bright light therapy. Trotti LM, Bliwise DL. Prolonged-release melatonin in patients with idiopathic REM sleep behavior disorder. Sleep. A study that evaluated three of these trials found gabapentin enacarbil 600mg to be significantly effective in reducing RLS severity after 12weeks of treatment compared to placebo [127]. eCollection 2023. 2003;4(4):281-4. Neurodegenerative processes within sleep regulatory brain circuitries, antiparkinsonian (e.g., levodopa and dopamine agonists) and concomitant medication (e.g., antidepressants) as well as comorbidities or other non-motor symptoms (such as depression) are discussed as causative factors. Daubian-Nose P, Frank MK, Esteves AM. 2019;15:2205-2212. Other sleep disorders such as RLS or RBD can also occur and negatively impact quality of life for both the patient and caretaker. Kushida CA, Littner MR, Morgenthaler T, Alessi CA, Bailey D, Coleman J, Jr, et al. Xiang W, Sun YQ, Teoh HC. Make a bedtime routine for example, snack, evening medication, tooth-brushing, using the restroom and follow it every evening. FOIA Kaminska M, Lafontaine AL, Kimoff RJ. The https:// ensures that you are connecting to the Circadian rhythm disorders may be more common in PD than previously thought, leading to late sleep times and increasing the risk of daytime sleepiness. Sleep Med. Sleep disorders in patients with Parkinson's disease (PD) are very common and have an immense negative impact on their quality of life. One study evaluating the impact of controlled-release levodopa/carbidopa on the severity of OSA in PD patients showed a trend toward reduction of the apnea-hypopnea index (AHI) in the treatment group, though the difference was not statistically significant [155]. 2015;30(10):1371-81. Sleep Med. 2009;301(1):63-73. Simultaneously, a good history should always be taken to look for primary sleep disorders and causes of secondary insomnia, mainly depression. The association is also not as strong as that observed in the synucleinopathies. Common Wearables Promising for Detection of Prodromal Parkinson's. Pallidal versus subthalamic deep-brain stimulation for Parkinsons disease. and transmitted securely. sleep problems, depression, memory difficulties, and fatigue. Treatment of these sleep disturbances often requires a multifaceted approach which depends on the specific issue. Ondo WG, Fayle R, Atassi F, Jankovic J. Modafinail for daytime somnolence in Parkinsons disease: double blind, placebo controlled parallel trial. These papers explore the important role of sleep in the progression and management of Parkinsons disease. and transmitted securely. Others are dementia with Lewy bodies, multiple system atrophy and pure autonomic failure. Your feedback is important to us. Sleep disruption, including REM-sleep behaviour disorder and circadian rhythm dysfunction, is a well-recognised prodromal aspect of PD, although other features such as restless leg syndrome and other physical factors may contribute. Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017). There's a question and answer session. In other cases, the disorder may be caused by something specific, such as obstructive sleep apnea, narcolepsy, psychiatric disorders, use of antidepressants, autoimmune disorders and brain lesions, which are areas of damaged brain tissue. Correlates of excessive daytime sleepiness in de novo Parkinsons disease: A case control study. After 12 years, 73.5 per cent of those with REM sleep behaviour disorder had developed a related neurodegenerative illness. The circadian rhythm is a roughly 24-h cycle that regulates physiologic and behavioral processes [6, 10]. 2011;26:399406. The PDSS-2 is a revised version that includes a severity scale and specific questions regarding restlessness, tremor, and cramping [13]. The PD and EDS groups also have worse scores on motor, nonmotor, autonomic, and cognitive testing [133, 139]. Zheyu Xu, Kirstie N. Anderson & Nicola Pavese, Claudio Liguori, Mariana Fernandes, Mariangela Pierantozzi, Zheyu Xu, Kirstie N. Anderson, Nicola Pavese, E. Matar, S. J. McCarter, S. J. G. Lewis, Jos Rafael P. Zuzurregui & Emmanuel H. During, Femke Dijkstra, Ilse de Volder, David Crosiers, Neurotherapeutics Some 60 per cent of patients and 20 per cent of bed partners of people with the disorder have sustained injuries during bed-time. 2019;64:220-225. Dopaminergic therapy has been shown to be related with activity rest rhythm alterations, mainly early morning awakenings among patients with PD. Schuepbach WM, Rau J, Knudsen K, et al. This study demonstrated that those with PD and EDS had a significantly lower overall score on the PDQ-39 than those without EDS (p<0.001), as well as individual emotional, social, and physical domains measured by this survey (p<0.01). 2012;26(9):773-80. Weaver FM, Follett K, Stern M, et al. Kunz D, Mahlberg R. A two-part, double-blind, placebo-controlled trial of exogens melatonin in REM sleep behaviour disorder. Iranzo A, Molinuevo JL, Santamara J, Serradell M, Mart MJ, Valldeoriola F, et al. Troubling Sleep Disorder in Athletes a Sign of CTE? PubMed Current evidence suggests that clonazepam and melatonin should continue to be used as first-line agents to treat RBD in PD (Fig. 2015;16(1):19-26. At follow-up, significantly decreased levels of CSF alpha-synuclein as compared to baseline were only seen in a subset of the patients (females with PD, prodromal PD patients specifically with dream-enactment behaviour, and healthy controls with daytime sleepiness). Kam, Varga, and co-authors report no relevant financial relationships. Ringman JM, Simmons JH. Some studies have also suggested an association of EDS in PD with depression [133, 137, 138]. A prospective, naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder. A full clinical history was also taken, focusing on sleep habits and risk factors that could contribute to sleep difficulties. Results from these small studies are promising, though larger follow-up studies are needed. Other agents that can worsen RBD include antipsychotics, barbiturates, alcohol, and caffeine [72]. Levodopa may cause augmentation in over 80% of patients based on early case series, while pramipexole and ropinirole may lead to this at a rate up to 10% per year [111, 122, 123]. CNS Drugs. This is in contrast with earlier studies that did not show improvement on PSG [92]. Mood and neural correlates of excessive daytime sleepiness in Parkinsons disease. Plan to spend seven to eight hours a night in bed. Treatment flow chart for rapid eye movement behavior disorder (RBD) in Parkinsons disease (PD). Amara AW, Wood KH, Joop A, Memon RA, Pilkington J, Tuggle SC, Reams J, Barrett MJ, Edwards DA, Weltman AL, Hurt CP, Cutter G, Bamman MM. Jun JS, Kim R, Byun JI, et al. [Sleep disturbances in Parkinson's disease]. J Clin Psychol.

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