Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest α-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of α-synucleinopathy patients with isolated RBD might develop.

Centre for Advanced Research in Sleep Medicine Centre intégré universitaire de santé et de services sociaux du Nord de l'Île de Montréal Hôpital du Sacré Coeur de Montréal Montreal QC Canada

Clinical Neurology DINOGMI University of Genoa Genoa Italy; IRCCS Ospedale Policlinico San Martino Genoa Italy

Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy

Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italy; UOC Clinica Neurologica Rete Metropolitana NEUROMET Bellaria Hospital Bologna Italy

Department of Circuit Theory Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

Department of Kinesiology Faculty of Applied Health Sciences University of Waterloo Waterloo ON Canada

Department of Medical Science and Public Health University of Cagliari Cagliari Italy

Department of Neurology and Center for Sleep Medicine Mayo Clinic Rochester MN USA

Department of Neurology and Center of Clinical Neuroscience Charles University 1st Faculty of Medicine Prague Czech Republic

Department of Neurology and Neurological Sciences and Department of Psychiatry and Behavioral Science Stanford University Palo Alto CA USA

Department of Neurology and Neurological Sciences University of California San Francisco CA USA; Department of Neurology Tel Aviv Sourasky Medical Center Affiliate of Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Department of Neurology and Section on Clinical Neuroscience Philipps University Marburg Marburg Germany

Department of Neurology and Section on Clinical Neuroscience Philipps University Marburg Marburg Germany; Institute for Neurogenomics Helmholtz Center for Health and Environment München Neuherberg Germany

Department of Neurology Kyung Hee University Hospital Seoul South Korea

Department of Neurology Mayo Clinic College of Medicine Scottsdale AZ USA

Department of Neurology Medical University of Innsbruck Innsbruck Austria

Department of Neurology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

Department of Neurology Seoul National University College of Medicine Seoul South Korea

Department of Neurology University of Minnesota Minneapolis MN USA

Department of Neurology University of Rostock Rostock Germany; German Center for Neurodegenerative Diseases Research Site Rostock Rostock Germany

Department of Neurology University of Würzburg Würzburg Germany

Department of Neuroscience Centre Hospitalier de Luxembourg Luxembourg City Luxembourg

Department of Neurosciences Biomedicine and Movement Sciences University of Verona Verona Italy

Department of Nuclear Medicine and Biomedical Imaging University Medical Center Groningen Groningen Netherlands

ForeFront Parkinson's Disease Research Clinic Brain and Mind Centre University of Sydney Sydney NSW Australia

Institute of Clinical Neurosciences University of Bristol Bristol UK

IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italy; Department of Biomedical Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy

Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK

Oasi Research Institute IRCCS Troina Italy

Sleep Disorders Center Neurology Service Hospital Clínic Barcelona Universitat de Barcelona Barcelona Spain

Sleep Medicine Center Department of Systems Medicine University of Rome Tor Vergata Rome Italy

The Neuro Montreal Neurological Institute Hospital Department of Neurology and Neurosurgery and Department of Human Genetics McGill University Montreal QC Canada

Komentář v

Lancet Neurol. 2021 Aug;20(8):593-594. doi: 10.1016/S1474-4422(21)00201-5. PubMed

Zobrazit více v PubMed

Postuma RB, Iranzo A, Hu M, et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain 2019; 142: 744–59. PubMed PMC

Califf RM. Biomarker definitions and their applications. Exp Biol Med (Maywood) 2018; 243: 213–21. PubMed PMC

Ferri R, Aricò D, Cosentino FII, Lanuzza B, Chiaro G, Manconi M. REM sleep without atonia with REM sleep-related motor events: broadening the spectrum of REM sleep behavior disorder. Sleep 2018; 41: zsy187. PubMed

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

Nepozitek J, Dostalova S, Dusek P, et al. Simultaneous tonic and phasic REM sleep without atonia best predicts early phenoconversion to neurodegenerative disease in idiopathic REM sleep behavior disorder. Sleep 2019; 42: zsz132. PubMed

McCarter SJ, Sandness DJ, McCarter AR, et al. REM sleep muscle activity in idiopathic REM sleep behavior disorder predicts phenoconversion. Neurology 2019; 93: e1171–79. PubMed PMC

Peever J, Luppi PH, Montplaisir J. Breakdown in REM sleep circuitry underlies REM sleep behavior disorder Trends Neurosci 2014; 37: 279–88. PubMed

Melpignano A, Parrino L, Santamaria J, et al. Isolated rapid eye movement sleep behavior disorder and cyclic alternating pattern: is sleep microstructure a predictive parameter of neurodegeneration? Sleep 2019; 42: zsz142. PubMed

Ruffini G, Ibañez D, Castellano M, et al. Deep learning with EEG spectrograms in rapid eye movement behavior disorder. Front Neurol 2019; 10: 806. PubMed PMC

Cooray N, Andreotti F, Lo C, Symmonds M, Hu MTM, De Vos M. Detection of REM sleep behaviour disorder by automated polysomnography analysis. Clin Neurophysiol 2019; 130: 505–14. PubMed

Lanza G, Aricò D, Lanuzza B, et al. Fadlitatory/inhibitory intracortical imbalance in REM sleep behavior disorder early electrophysiological marker of neurodegeneration? Sleep 2020; 43: zsz242. PubMed

Puligheddu M, FigorilH M, Serra A, et al. REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder Sleep 2019; 42: zsz128. PubMed

Fereshtehnejad SM, Yao C, Pelletier A, Montplaisir JY, Gagnon JF, Postuma RB. Evolution of prodromal Parkinson’s disease and dementia with Lewy bodies: a prospective study. Brain 2019; 142: 2051–67. PubMed

Del Din S, Yamall AJ, Barber TR, et al. Continuous real-world gait monitoring in idiopathic REM sleep behavior disorder. J Parkinsons Dis 2020; 10: 283–99. PubMed

Ehgoetz Martens KA, Matar E, Hall JM, et al. Subtle gait and balance impairments occur in idiopathic rapid eye movement sleep behavior disorder. Mov Disord 2019; 34: 1374–80. PubMed

Rusz J, Hlavnicka J, Tykalova T, et al. Smartphone allows capture of speech abnormalities associated with high risk of developing Parkinson’s disease. IEEE Trans Neural Syst Rehabil Eng 2018; 26: 1495–507. PubMed

Hanuška J, Rusz J, Bezdicek O, et al. Eye movements in idiopathic rapid eye movement sleep behaviour disorder: high antisaccade error rate reflects prefrontal cortex dysfunction. J Sleep Res 2019; 28: e12742. PubMed

Arora S, Baig F, Lo C, et al. Smartphone motor testing to distinguish idiopathic REM sleep behavior disorder, controls, and PD. Neurology 2018; 91: e1528–38. PubMed PMC

Krupička R, Krýže P, Net’uková S, et al. Instrumental analysis of finger tapping reveals a novel early biomarker of parkinsonism in idiopathic rapid eye movement sleep behaviour disorder. Sleep Med 2020; 75: 45–9. PubMed

Cochen De Cock V, de Verbizier D, Picot MC, et al. Rhythm disturbances as a potential early marker of Parkinson’s disease in idiopathic REM sleep behavior disorder. Ann Clin Transl Neurol 2020; 7: 280–87. PubMed PMC

Ferini-Strambi L, Fasiello E, Sforza M, Salsone M, Galbiati A. Neuropsychological, electrophysiological, and neuroimaging biomarkers for REM behavior disorder Expert Rev Neurother 2019; 19: 1069–87. PubMed

Terzaghi M, Toscano G, Casoni F, et al. Assessment of cognitive profile as a prodromal marker of the evolution of rapid eye movement sleep behavior disorder. Sleep 2019; 42: zsz103. PubMed

Génier Marchand D, Montplaisir J, Postuma RB, Rahayel S, Gagnon JF. Detecting the cognitive prodrome of dementia with Lewy bodies: a prospective study of REM sleep behavior disorder. Sleep 2017; 40: zsw014. PubMed

Génier Marchand D, Postuma RB, Escudier F, et al. How does dementia with Lewy bodies start? Prodromal cognitive changes in REM sleep behavior disorder. Ann Neurol 2018; 83: 1016–26. PubMed

Honeycutt L, Gagnon JF, Pelletier A, De Roy J, Montplaisir JY, Postuma RB. Pareidolias and cognition in isolated REM sleep behavior disorder. Parkinsonism Relat Disord 2020; 75: 76–79. PubMed

Bezdicek O, Nikolai T, Nepožitek J, et al. Prospective memory impairment in idiopathic REM sleep behavior disorder. Clin Neuropsychol 2018; 32: 1019–37. PubMed

Barber TR, Lawton M, Rolinski M, et al. Prodromal parkinsonism and neurodegenerative risk stratification in REM sleep behavior disorder. Sleep 2017; 40: zsx071. PubMed PMC

Dušek P, Ibarburu VLYL, Bezdicek O, et al. Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder. Sci Rep 2019; 9: 15463. PubMed PMC

Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 1997; 22: 39–52. PubMed

Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L. Smell identification ability: changes with age. Science 1984; 226: 1441–43. PubMed

Sasai-Sakuma T, Takeuchi N, Asai Y, Inoue Y, Inoue Y. Prevalence and clinical characteristics of REM sleep behavior disorder in Japanese elderly people. Sleep 2020; 43: zsaa024. PubMed

Postuma RB, Gagnon JF, Bertrand JA, Génier Marchand D, Montplaisir JY. Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology 2015; 84: 1104–13. PubMed PMC

Iranzo A, Serradell M, Vilaseca I, et al. Longitudinal assessment of olfactory function in idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord 2013; 19: 600–04. PubMed

Shin C, Lee JY, Kim YK, et al. Cognitive decline in association with hyposmia in idiopathic rapid eye movement sleep behavior disorder: a prospective 2-year follow-up study. Eur J Neurol 2019; 26: 1417–20. PubMed

Doppler K, Jentschke HM, Schulmeyer L, et al. Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson’s disease. Acta Neuropathol 2017; 133: 535–45. PubMed PMC

Iranzo A, Marrero-González P, Serradell M, Gaig C, Santamaria J, Vilaseca I. Significance of hyposmia in isolated REM sleep behavior disorder.; Neurol 2021; 268: 963–66. PubMed

Jennings D, Siderowf A, Stem M, et al. Conversion to Parkinson disease in the PARS Hyposmie and Dopamine Transporter-Deficit Prodromal Cohort. JAMA Neurol 2017; 74: 933–40. PubMed PMC

Horgusluoglu E, Nudelman K, Nho K, Saykin AJ. Adult neurogenesis and neurodegenerative diseases: a systems biology perspective. Am J Med Genet B Neuropsychiatr Genet 2017; 174: 93–112. PubMed PMC

Postuma RB, Gagnon JE, Venderte M, Desjardins C, Montplaisir JY. Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol 2011; 69: 811–18. PubMed

Lee JY, Ahn J, Oh S, et al. Retina thickness as a marker of neurodegeneration in prodromal Lewy body disease. Mov Disord 2020; 35: 349–54. PubMed

Ahn J, Lee JY, Kim TW, et al. Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology 2018; 91: e1003–12. PubMed

Yang ZJ, Wei J, Mao CJ, et al. Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson’s disease. Sleep Breath 2016; 20: 1285–92. PubMed

Lee JY, Ahn J, Yoon EJ, Oh S, Kim YK, Jeon B. Macular ganglion-cell-complex layer thinning and optic nerve integrity in drug-naive Parkinson’s disease. J Neural Transm (Vienna) 2019; 126: 1695–99. PubMed

Mailankody P, Lenka A, Pal PK. The role of optical coherence tomography in parkinsonism: a critical review. J Neurol Sci 2019; 403: 67–74. PubMed

Cheung CY, Chan VTT, Mok VC, Chen C, Wong TY. Potential retinal biomarkers for dementia: what is new? Curr Opin Neurol 2019; 32: 82–91. PubMed

Ortuño-Lizarán I, Beach TG, Serrano GE, Walker DG, Adler CH, Cuenca N. Phosphorylated α-synuclein in the retina is a biomarker of Parkinson’s disease pathology severity. Mov Disord 2018; 33: 1315–24. PubMed PMC

Ferini-Strambi L, Oertel W, Dauvilliers Y, et al. Autonomic symptoms in idiopathic REM behavior disorder: a multicentre case-control study. J Neurol 2014; 261: 1112–18. PubMed

Li Y, Kang W, Yang Q, et al. Predictive markers for early conversion of iRBD to neurodegenerative synucleinopathy diseases. Neurology 2017; 88: 1493–500. PubMed PMC

McCarter SJ, Gehrking TL, St Louis EK, et al. Autonomic dysfunction and phenoconversion in idiopathic REM sleep behavior disorder. Clin Auton Res 2020; 30: 207–13. PubMed PMC

Zitser J, During EH, Chiaro G, Miglis MG. Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder Auton Neurosci 2019; 220: 102553. PubMed

Knudsen K, Fedorova TD, Hansen AK, et al. In-vivo staging of pathology in REM sleep behaviour disorder: a multimodaHty imaging case-control study. Lancet Neurol 2018; 17: 618–28. PubMed

Lee H, Cho YW, Kim HA. The severity and pattern of autonomic dysfunction in idiopathic rapid eye movement sleep behavior disorder: Mov Disord 2015; 30: 1843–48. PubMed

Rocchi C, Placidi F, liguori C, et al. Daytime autonomic activity in idiopathic rapid eye movement sleep behavior disorder: a preliminary study. Sleep Med 2018; 52: 163–67. PubMed

Zitser J, Muppidi S, Sinn DI, Jaradeh S, Miglis MG. Quantitative sudomotor abnormalities in clinically isolated rapid eye movement sleep behavior disorder: Auton Neurosci 2020; 224: 102645. PubMed

Rossi M, Candelise N, Baiardi S, et al. Ultrasensitive RT-QulC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies. Acta Neuropathol 2020; 140: 49–62. PubMed PMC

Iranzo A, Fairfoul G, Ayudhaya ACN, et al. Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurol 2021; 20: 203–12. PubMed

Stefani A, Iranzo A, Holzknecht E, et al. Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder: Brain 2021; 144: 1118–26. PubMed

Niu M, Ii Y, Ii G, et al. A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson’s disease development and progression. Eur J Neurol 2020; 27: 967–74. PubMed

Jiang C, Hopfner F, Katsikoudi A, et al. Serum neuronal exosomes predict and differentiate Parkinson’s disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry 2020; 91: 720–29. PubMed PMC

Wilke C, Dos Santos MCT, Schulte C, et al. Intraindividual neurofilament dynamics in serum mark the conversion to sporadic Parkinson’s disease. Mov Disord 2020; 35: 1233–38. PubMed

Mondello S, Kobeissy F, Mechref Y, et al. Novel biomarker signatures for idiopathic REM sleep behavior disorder: a proteomic and system biology approach. Neurology 2018; 91: e1710–15. PubMed

Dong X, Mondello S, Kobeissy F, Talih F, Ferri R, Mechref Y. LC-MS/MS glycomics of idiopathic rapid eye movement sleep behavior disorder: Electrophoresis 2018; 39: 3096–103. PubMed PMC

Fernández-Santiago R, Iranzo A, Gaig C, et al. MicroRN A association with synucleinopathy conversion in rapid eye movement behavior disorder. Ann Neurol 2015; 77: 895–901. PubMed

Smith AM, Depp C, Ryan BJ, et al. Mitochondrial dysfunction and increased glycolysis in prodromal and early Parkinson’s blood cells. Mov Disord 2018; 33: 1580–90. PubMed PMC

Heintz-Buschart A, Pandey U, Wicke T, et al. The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder: Mov Disord 2018; 33: 88–98. PubMed PMC

Amaldi D, Chincarini A, De Carli F, et al. The fate of patients with REM sleep behavior disorder and mild cognitive impairment. Sleep Med 2021; 79: 205–10. PubMed

Meles SK, Renken RJ, Janzen A, et al. The metabolic pattern of idiopathic REM sleep behavior disorder reflects early-stage Parkinson disease. J Nucl Med 2018; 59: 1437–44. PubMed

Rahayel S, Postuma RB, Montplaisir J, et al. Cortical and subcortical gray matter bases of cognitive deficits in REM sleep behavior disorder: Neurology 2018; 90: e1759–70. PubMed PMC

Iranzo A, Valldeoriola F, Lomeña F, et al. Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 2011; 10: 797–805. PubMed

Iranzo A, Santamaría J, Valldeoriola F, et al. Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder: Ann Neurol 2017; 82: 419–28. PubMed

Amaldi D, Chincarini A, Hu MT, et al. Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder: Brain 2021; 144: 278–87. PubMed PMC

Huang Z, Jiang C, Ii L, et al. Correlations between dopaminergic dysfunction and abnormal metabolic network activity in REM sleep bkiavior disorder: J Cereb Blood Flow Metab 2020; 40: 552–62. PubMed PMC

Kogan RV, Janzen A, Meles SK, et al. Four-year follow-up of [18F] fluorodeoxyglucose positron emission tomography-based Parkinson’s disease-related pattern expression in 20 patients with isolated rapid eye movement sleep behavior disorder shows prodromal progression. Mov Disord 2021; 36: 230–35. PubMed PMC

Barber TR, Griffanti L, Bradley KM, et al. Nigrosome 1 imaging in REM sleep behavior disorder and its association with dopaminergic decline. Ann Clin Transl Neurol 2020; 7: 26–35. PubMed PMC

Rahayel S, Postuma RB, Montplaisir J, et al. Abnormal gray matter shape, thickness, and volume in the motor cortico-subcortical loop in idiopathic rapid eye movement sleep behavior disorder: association with clinical and motor features. Cereb Cortex 2018; 28: 658–71. PubMed

Rahayel S, Postuma RB, Montplaisir J, et al. A Prodromal brain-clinical pattern of cognition in synucleinopathies. Ann Neurol 2021; 89: 341–57. PubMed

Muñoz-Lopetegi A, Berenguer J, Iranzo A, et al. Magnetic resonance imaging abnormalities as a marker of multiple system atrophy in isolated rapid eye movement sleep behavior disorder: Sleep 2021; 44: zsaa089. PubMed

Campabadal A, Abos A, Segura B, et al. Disruption of posterior brain functional connectivity and its relation to cognitive impairment in idiopathic REM sleep behavior disorder. Neuroimage Clin 2020; 25: 102138. PubMed PMC

Gersel Stokholm M, Iranzo A, Østergaard K, et al. Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder. Eur J Neurol 2020; 27: 644–52. PubMed

Beach TG, Adler CH, Sue LI, et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 2010; 119: 689–702. PubMed PMC

Zitser J, Gibbons C, Miglis MG. The role of tissue biopsy as a biomarker in REM sleep behavior disorder. Sleep Med Rev 2020; 51: 101283. PubMed

Sprenger FS, Stefanova N, Gelpi E, et al. Enteric nervous system α-synuclein immunoreactivity in idiopathic REM sleep behavior disorder. Neurology 2015; 85: 1761–68. PubMed PMC

Vilas D, Iranzo A, Tolosa E, et al. Assessment of α-synuclein in submandibular glands of patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol 2016; 15: 708–18. PubMed

Iranzo A, Borrego S, Vilaseca I, et al. α-Synuclein aggregates in labial salivary glands of idiopathic rapid eye movement sleep behavior disorder: Sleep 2018; 41: zsy101. PubMed

Antelmi E, Donadio V, Incensi A, Plazzi G, Liguori R. Skin nerve phosphorylated α-synuclein deposits in idiopathic REM sleep behavior disorder: Neurology 2017; 88: 2128–31. PubMed

Antelmi E, Pizza F, Donadio V, et al. Biomarkers for REM sleep behavior disorder in idiopathic and narcoleptic patients. Ann Clin Transl Neurol 2019; 6: 1872–76. PubMed PMC

Al-Qassabi A, Tsao TS, Racolta A, et al. Immunohistochemical detection of synuclein pathology in skin in idiopathic rapid eye movement sleep behavior disorder and parkinsonism. Mov Disord 2021; 36: 895–904. PubMed PMC

Donadio V, Doppler K, Incensi A, et al. Abnormal α-synuclein deposits in skin nerves: intra- and inter-laboratory reproducibility. Eur J Neurol 2019; 26: 1245–51. PubMed

Donadio V, Incensi A, Rizzo G, et al. Skin biopsy may help to distinguish multiple system atrophy-parkinsonism from Parkinson’s disease with orthostatic hypotension. Mov Disord 2020; 35: 1649–57. PubMed

Ouled Amar Bencheikh B, Ruskey JA, Amulf I, et al. LRRK2 protective haplotype and full sequencing study in REM sleep behavior disorder: Parkinsonism Relat Disord 2018; 52: 98–101. PubMed

Li J, Ruskey JA, Amulf I, et al. Full sequencing and haplotype analysis of MAPT in Parkinson’s disease and rapid eye movement sleep behavior disorder. Mov Disord 2018; 33: 1016–20. PubMed

Gan-Or Z, Montplaisir JY, Ross JP, et al. The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep behavior disorder: Neurobiol Aging 2017; 49: 218.e13–15. PubMed

Gan-Or Z, Mirelman A, Postuma RB, et al. GB A mutations are associated with rapid eye movement sleep behavior disorder. Ann Clin Transl Neurol 2015; 2: 941–45. PubMed PMC

Krohn L, Öztürk TN, Vanderperre B, et al. Genetic, structural, and functional evidence link TMEM175 to synucleinopathies. Ann Neurol 2020; 87: 139–53. PubMed

Krohn L, Ruskey JA, Rudakou U, et al. GBA variants in REM sleep behavior disorder: a multicenter study. Neurology 2020; 95: e1008–16. PubMed PMC

Rrohn L, Wu RYJ, Heilbron K, et al. Fine-mapping of SNCA in rapid eye movement sleep behavior disorder and overt synudeinopathies. Ann Neurol 2020; 87: 584–98. PubMed PMC

Ferri R, Gagnon JF, Postuma RB, Rundo F, Montplaisir JY. Comparison between an automatic and a visual scoring method of the chin musde tone during rapid eye movement sleep. Sleep Med 2014; 15: 661–65. PubMed

Ferri R, Fulda S, Manconi M, et al. Night-to-night variability of periodic leg movements during sleep in restless legs syndrome and periodic limb movement disorder: comparison between the periodicity index and the PLMS index. Sleep Med 2013; 14: 293–96. PubMed

Ferri R, Marelli S, Cosentino FI I, Rundo F, Ferini-Strambi L, Zucconi M. Night-to-night variability of automatic quantitative parameters of the chin EMG amplitude (atonia index) in REM sleep behavior disorder. J Clin Sleep Med 2013; 9: 253–58. PubMed PMC

Figorilh M, Marques AR, Meloni M, et al. Diagnosing REM sleep behavior disorder in Parkinson’s disease without a gold standard: a latent-dass model study. Sleep 2020; 43: zsz323. PubMed

Frauscher B, Gabelia D, Biermayr M, et al. Validation of an integrated software for the detection of rapid eye movement sleep behavior disorder. Sleep 2014; 37: 1663–71. PubMed PMC

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. PubMed PMC

Khalil A, Wright MA, Walker MC, Eriksson SH. Loss of rapid eye movement sleep atonia in patients with REM sleep behavioral disorder, narcolepsy, and isolated loss of REM atonia. J Clin Sleep Med 2013; 9: 1039–48. PubMed PMC

McCarter SJ, St Louis EK, Duwell EJ, et al. Diagnostic thresholds for quantitative REM sleep phasic burst duration, phasic and tonic muscle activity, and REM atonia index in REM sleep behavior disorder with and without comorbid obstructive sleep apnea. Sleep (Basel) 2014; 37: 1649–62. PubMed PMC

McCarter SJ, St Louis EK, Sandness DJ, et al. Diagnostic REM sleep muscle activity thresholds in patients with idiopathic REM sleep behavior disorder with and without obstructive sleep apnea. Sleep Med 2017; 33: 23–29. PubMed PMC

Campabadal A, Segura B, Junque C, et al. Comparing the accuracy and neuroanatomical correlates of the UPSIT-40 and the Sniffin’ Sticks test in REM sleep behavior disorder. Parkinsonism Relat Disord 2019; 65: 197–202. PubMed

Lawton M, Hu MT, Baig F, et al. Equating scores of the University of Pennsylvania Smell Identification Test and Sniffin’ Sticks test in patients with Parkinson’s disease. Parkinsonism Relat Disord 2016; 33: 96–101. PubMed PMC

Pyatigorskaya N, Gaurav R, Amaldi D, et al. Magnetic resonance imaging biomarkers to assess substantia nigra damage in idiopathic rapid eye movement sleep behavior disorder. Sleep 2017; 40: zsx149. PubMed

Amaldi D, Famà F, Girder N, et al. Rapid eye movement sleep behavior disorder: a proof-of-concept neuroprotection study for prodromal synudeinopathies. Eur J Neurol 2021; 28: 1210–17. PubMed

Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy

Magnetic susceptibility changes in the brainstem reflect REM sleep without atonia severity in isolated REM sleep behavior disorder

Articulatory undershoot of vowels in isolated REM sleep behavior disorder and early Parkinson's disease

Study protocol for using a smartphone application to investigate speech biomarkers of Parkinson's disease and other synucleinopathies: SMARTSPEECH

Increased Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder