REFERENCES
1. Lee WJ, Baek SH, Im HJ, et al. REM sleep behavior disorder and its possible prodromes in general population: prevalence, polysomnography findings, and associated factors. Neurology. 2023;101:e2364-75.
2. Stefani A, Antelmi E, Arnaldi D, et al. From mechanisms to future therapy: a synopsis of isolated REM sleep behavior disorder as early synuclein-related disease. Mol Neurodegener. 2025;20:19.
3. 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.
4. Miglis MG, Adler CH, Antelmi E, et al. Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder. Lancet Neurol. 2021;20:671-84.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Iranzo A, Serradell M, Vilaseca I, et al. Longitudinal assessment of olfactory function in idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord. 2013;19:600-4.
11. Jennings D, Siderowf A, Stern M, et al; PARS Investigators. Conversion to Parkinson disease in the PARS hyposmic and dopamine transporter-deficit prodromal cohort. JAMA Neurol. 2017;74:933-40.
12. Postuma RB, Lang AE, Massicotte-Marquez J, Montplaisir J. Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder. Neurology. 2006;66:845-51.
13. Postuma RB, Gagnon JF, Vendette M, Desjardins C, Montplaisir JY. Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol. 2011;69:811-8.
14. 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.
15. 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.
16. La Morgia C, Romagnoli M, Pizza F, et al. Chromatic pupillometry in isolated rapid eye movement sleep behavior disorder. Mov Disord. 2022;37:205-10.
17. Lee H, Cho YW, Kim HA. The severity and pattern of autonomic dysfunction in idiopathic rapid eye movement sleep behavior disorder. Mov Disord. 2015;30:1843-8.
18. 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.
19. Pilotto A, Romagnolo A, Tuazon JA, et al. Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies. J Neurol Neurosurg Psychiatry. 2019;90:1257-63.
20. Dahms C, Guenther A, Schwab M, et al. Dysautonomia in prodromal α-synucleinopathy: peripheral versus central autonomic degeneration. Eur J Neurol. 2016;23:878-90.
21. Taha HB, Zitser J, Miglis MG. Frequency and longitudinal course of autonomic reflex testing abnormalities in isolated rem sleep behavior disorder. Sleep. 2025:zsaf087.
22. Zhou J, Zhang J, Lam SP, et al. Excessive daytime sleepiness predicts neurodegeneration in idiopathic REM sleep behavior disorder. Sleep. 2017;40:zsx041.
23. Postuma RB, Gagnon JF, Pelletier A, Montplaisir JY. Insomnia and somnolence in idiopathic RBD: a prospective cohort study. NPJ Parkinsons Dis. 2017;3:9.
24. Lerche S, Machetanz G, Roeben B, et al. Deterioration of executive dysfunction in elderly with REM sleep behavior disorder (RBD). Neurobiol Aging. 2018;70:242-6.
25. Nagy AV, Leschziner G, Eriksson SH, Lees A, Noyce AJ, Schrag A. Cognitive impairment in REM-sleep behaviour disorder and individuals at risk of Parkinson’s disease. Parkinsonism Relat Disord. 2023;109:105312.
26. Génier Marchand D, Postuma RB, Escudier F, et al. How does dementia with Lewy bodies start? Ann Neurol. 2018;83:1016-26.
27. Wang J, Huang B, Zhou L, et al. Visuospatial dysfunction predicts dementia-first phenoconversion in isolated REM sleep behaviour disorder. J Neurol Neurosurg Psychiatry. 2024;96:76-84.
28. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB consortium. Neurology. 2017;89:88-100.
29. Arnulf I. Dream imagery, rapid eye movement sleep behavior disorder, and hallucinations: dreaming, visual hallucinations and RBD. Sleep Biol Rhythms. 2013;11:15-20.
30. Williams DR, Lees AJ. Visual hallucinations in the diagnosis of idiopathic Parkinson’s disease: a retrospective autopsy study. Lancet Neurol. 2005;4:605-10.
31. Uchiyama M, Nishio Y, Yokoi K, et al. Pareidolias: complex visual illusions in dementia with Lewy bodies. Brain. 2012;135:2458-69.
32. Ozawa M, Shiraishi T, Murakami H, et al. Structural MRI study of pareidolia and visual hallucinations in drug-naïve Parkinson’s disease. Sci Rep. 2024;14:31293.
33. Sasai-Sakuma T, Nishio Y, Yokoi K, Mori E, Inoue Y. Pareidolias in REM sleep behavior disorder: a possible predictive marker of Lewy body diseases? Sleep. 2017:40.
34. 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;75:76-9.
35. Wang J, Chau SWH, Lam SP, et al. Prevalence and correlates of REM sleep behaviour disorder in patients with major depressive disorder: a two-phase study. J Neurol Neurosurg Psychiatry. 2022;93:1010-7.
36. Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB; MDS task force on the definition of Parkinson’s disease. Update of the MDS research criteria for prodromal Parkinson’s disease. Mov Disord. 2019;34:1464-70.
37. Wang J, Lam SP, Huang B, et al. Familial α-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder. J Neurol Neurosurg Psychiatry. 2023;94:893-903.
38. Fantini ML, Gagnon JF, Petit D, et al. Slowing of electroencephalogram in rapid eye movement sleep behavior disorder. Ann Neurol. 2003;53:774-80.
39. Rodrigues Brazète J, Montplaisir J, Petit D, et al. Electroencephalogram slowing in rapid eye movement sleep behavior disorder is associated with mild cognitive impairment. Sleep Med. 2013;14:1059-63.
40. Roascio M, Canessa A, Trò R, et al. Phase and amplitude electroencephalography correlations change with disease progression in people with idiopathic rapid eye-movement sleep behavior disorder. Sleep. 2022:45.
41. Brazète J, Gagnon JF, Postuma RB, Bertrand JA, Petit D, Montplaisir J. Electroencephalogram slowing predicts neurodegeneration in rapid eye movement sleep behavior disorder. Neurobiol Aging. 2016;37:74-81.
42. Liu Y, Zhang J, Chau SWH, et al. Evolution of prodromal REM sleep behavior disorder to neurodegeneration: a retrospective longitudinal case-control study. Neurology. 2022;99:e627-37.
43. Liu Y, Zhang J, Lam SP, et al. Electromyography activity level in rapid eye movement sleep predicts neurodegenerative diseases in idiopathic rapid eye movement sleep behavior disorder: a 5-year longitudinal study. Sleep Med. 2019;56:128-34.
44. Singh A, Williams S, Calabrese A, Riha R. Tonic REM sleep muscle activity is the strongest predictor of phenoconversion risk to neurodegenerative disease in isolated REM sleep behaviour disorder. J Sleep Res. 2023;32:e13792.
45. 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.
46. Chahine LM, Brumm MC, Caspell-Garcia C, et al. Dopamine transporter imaging predicts clinically-defined α-synucleinopathy in REM sleep behavior disorder. Ann Clin Transl Neurol. 2021;8:201-12.
47. Hsiao IT, Weng YH, Lin WY, et al. Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson’s disease patients. Nucl Med Biol. 2014;41:322-9.
48. Beauchamp LC, Villemagne VL, Finkelstein DI, et al. Reduced striatal vesicular monoamine transporter 2 in REM sleep behavior disorder: imaging prodromal parkinsonism. Sci Rep. 2020;10:17631.
49. Beauchamp LC, Dore V, Villemagne VL, et al. Using (18)F-AV-133 VMAT2 PET imaging to monitor progressive nigrostriatal degeneration in Parkinson disease. Neurology. 2023;101:e2314-24.
50. Dang-Vu TT, Gagnon JF, Vendette M, Soucy JP, Postuma RB, Montplaisir J. Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder. Neurology. 2012;79:2302-6.
51. Rahayel S, Postuma R, Baril AA, et al. (99m)Tc-HMPAO SPECT perfusion signatures associated with clinical progression in patients with isolated REM sleep behavior disorder. Neurology. 2024;102:e208015.
52. Peralta C, Biafore F, Depetris TS, Bastianello M. Recent advancement and clinical implications of 18FDG-PET in Parkinson’s disease, atypical Parkinsonisms, and other movement disorders. Curr Neurol Neurosci Rep. 2019;19:56.
53. Holtbernd F, Gagnon JF, Postuma RB, et al. Abnormal metabolic network activity in REM sleep behavior disorder. Neurology. 2014;82:620-7.
54. Shin JH, Lee JY, Kim YK, et al. Parkinson disease-related brain metabolic patterns and neurodegeneration in isolated REM sleep behavior disorder. Neurology. 2021;97:e378-88.
55. Tang CC, Nakano Y, Vo A, et al. Longitudinal network changes and phenoconversion risk in isolated REM sleep behavior disorder. Nat Commun. 2024;15:10797.
56. Stær K, Iranzo A, Stokholm MG, et al. Microglial activation and progression of nigrostriatal dysfunction in isolated REM sleep behavior disorder. Mov Disord. 2024;39:1323-8.
57. Park DG, Kim JY, Kim MS, et al. Neurofilament light chain and cardiac MIBG uptake as predictors for phenoconversion in isolated REM sleep behavior disorder. J Neurol. 2023;270:4393-402.
58. Campabadal A, Segura B, Junque C, Iranzo A. Structural and functional magnetic resonance imaging in isolated REM sleep behavior disorder: a systematic review of studies using neuroimaging software. Sleep Med Rev. 2021;59:101495.
59. Zhang D, Yao J, Sun J, et al. Quantitative susceptibility mapping and free water imaging of substantia nigra in Parkinson’s disease. J Parkinsons Dis. 2022;12:2469-78.
60. Zhou L, Li G, Zhang Y, et al. Increased free water in the substantia nigra in idiopathic REM sleep behaviour disorder. Brain. 2021;144:1488-97.
61. Zhang D, Zhou L, Yao J, et al. Increased free water in the putamen in idiopathic REM sleep behavior disorder. Mov Disord. 2023;38:1645-54.
62. Takahashi H, Kashiwagi N, Arisawa A, et al. Imaging of the nigrostriatal system for evaluating the preclinical phase of Parkinson’s disease development: the utility of neuromelanin, diffusion MRI, and DAT-SPECT. Br J Radiol. 2022;95:20210837.
63. Ehrminger M, Latimier A, Pyatigorskaya N, et al. The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder. Brain. 2016;139:1180-8.
64. Biondetti E, Gaurav R, Yahia-Cherif L, et al. Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease. Brain. 2020;143:2757-70.
65. Iwanami M, Miyamoto T, Miyamoto M, Hirata K, Takada E. Relevance of substantia nigra hyperechogenicity and reduced odor identification in idiopathic REM sleep behavior disorder. Sleep Med. 2010;11:361-5.
66. Iranzo A, Stockner H, Serradell M, et al. Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder. Mov Disord. 2014;29:1774-80.
67. 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;91:720-9.
68. Li Y, Cao Y, Liu W, et al. Candidate biomarkers of EV-microRNA in detecting REM sleep behavior disorder and Parkinson’s disease. NPJ Parkinsons Dis. 2024;10:18.
69. Zhang X, Ma L, Liang D, et al. Neurofilament light protein predicts disease progression in idiopathic REM sleep behavior disorder. J Parkinsons Dis. 2023;13:485-99.
70. Arnaldo L, Mena J, Serradell M, et al. Platelet miRNAs as early biomarkers for progression of idiopathic REM sleep behavior disorder to a synucleinopathy. Sci Rep. 2025;15:12136.
71. Gámez-Valero A, Campdelacreu J, Vilas D, et al. Platelet miRNA biosignature discriminates between dementia with Lewy bodies and Alzheimer’s disease. Biomedicines. 2021;9:1272.
72. 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:e1710-5.
73. Hällqvist J, Bartl M, Dakna M, et al. Plasma proteomics identify biomarkers predicting Parkinson’s disease up to 7 years before symptom onset. Nat Commun. 2024;15:4759.
74. Zhang H, Wang T, Li Y, et al. Plasma immune markers in an idiopathic REM sleep behavior disorder cohort. Parkinsonism Relat Disord. 2020;78:145-50.
75. Delva A, Pelletier A, Somerville E, et al. Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder. Brain. 2025;148:2049-59.
76. 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.
77. Zheng Y, Yu Z, Cai H, et al. Detection of α-synuclein in oral mucosa by seed amplification assay in synucleinopathies and isolated REM sleep behavior disorder. Mov Disord. 2024;39:1300-9.
78. Concha-Marambio L, Weber S, Farris CM, et al. Accurate detection of α-synuclein seeds in cerebrospinal fluid from isolated rapid eye movement sleep behavior disorder and patients with Parkinson’s disease in the DeNovo Parkinson (DeNoPa) cohort. Mov Disord. 2023;38:567-78.
79. 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.
80. Iranzo A, Mammana A, Muñoz-Lopetegi A, et al. Misfolded α-synuclein assessment in the skin and CSF by RT-QuIC in isolated rem sleep behavior disorder. Neurology. 2023;100:e1944-54.
81. Kumru H, Santamaria J, Tolosa E, et al. Rapid eye movement sleep behavior disorder in parkinsonism with parkin mutations. Ann Neurol. 2004;56:599-603.
82. Barber TR, Lawton M, Rolinski M, et al. Prodromal Parkinsonism and neurodegenerative risk stratification in REM sleep behavior disorder. Sleep. 2017:40.
83. Li J, Ruskey JA, Arnulf 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.
84. Krohn L, Heilbron K, Blauwendraat C, et al; 23andMe Research Team. Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects. Nat Commun. 2022;13:7496.
85. Krohn L, Wu RYJ, Heilbron K, et al; 23andMe Research Team. Fine-mapping of snca in rapid eye movement sleep behavior disorder and overt synucleinopathies. Ann Neurol. 2020;87:584-98.
86. Thaler A, Bregman N, Gurevich T, et al. Parkinson’s disease phenotype is influenced by the severity of the mutations in the GBA gene. Parkinsonism Relat Disord. 2018;55:45-9.
87. Honeycutt L, Montplaisir JY, Gagnon JF, et al. Glucocerebrosidase mutations and phenoconversion of REM sleep behavior disorder to parkinsonism and dementia. Parkinsonism Relat Disord. 2019;65:230-3.
88. Li Y, Hao S, Zhang H, et al. Hypomethylation of SNCA in idiopathic REM sleep behavior disorder associated with phenoconversion. Mov Disord. 2021;36:955-62.
89. Zhou L, Chau SWH, Liu Y, et al. Personality profile and its association with conversion to neurodegenerative disorders in idiopathic REM sleep behavior disorder. NPJ Parkinsons Dis. 2022;8:91.
90. Zhou L, Li SX, Chau SW, et al. Altered impulsivity across drug-naïve parkinsonism, isolated rapid eye movement sleep behavior disorder, and their high-risk relatives. Ann Neurol. 2024;95:544-57.
91. Wang J, Liu Y, Chau SWH, et al. Residual injurious symptoms and its association with neurodegenerative outcomes in idiopathic rapid eye movement sleep behavior disorder: a retrospective, longitudinal follow-up study. Mov Disord. 2020;35:2077-85.
92. Leng Y, Musiek ES, Hu K, Cappuccio FP, Yaffe K. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol. 2019;18:307-18.
93. Hughes KC, Gao X, Molsberry S, Valeri L, Schwarzschild MA, Ascherio A. Physical activity and prodromal features of Parkinson disease. Neurology. 2019;93:e2157-69.
94. Feng H, Chen L, Liu Y, et al. Rest-activity pattern alterations in idiopathic REM sleep behavior disorder. Ann Neurol. 2020;88:817-29.
95. Carpi M, Fernandes M, Risino I, et al. Alteration of circadian sleep-wake rhythm and salivary melatonin secretion in idiopathic/isolated REM sleep behavior disorder: preliminary evidence. Sleep Med. 2024;119:135-8.
96. Weissová K, Škrabalová J, Skálová K, et al. Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder. Sleep Med. 2018;52:1-6.
97. Cryan JF, O'Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol. 2020;19:179-94.
98. Huang B, Chau SWH, Liu Y, et al. Gut microbiome dysbiosis across early Parkinson’s disease, REM sleep behavior disorder and their first-degree relatives. Nat Commun. 2023;14:2501.
99. Jeong E, Woo Shin Y, Byun JI, et al. EEG-based machine learning models for the prediction of phenoconversion time and subtype in isolated rapid eye movement sleep behavior disorder. Sleep. 2024;47:zsae031.
100. Gaurav R, Pyatigorskaya N, Biondetti E, et al. Deep learning-based neuromelanin MRI changes of isolated REM sleep behavior disorder. Mov Disord. 2022;37:1064-9.
101. Abdelfattah M, Zhou L, Sum-Ping O, et al. Automated detection of isolated REM sleep behavior disorder using computer vision. Ann Neurol. 2025;97:860-72.
102. Arnaldi D, Chincarini A, Hu MT, et al. Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder. Brain. 2021;144:278-87.
103. 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.
104. 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.
105. Kogan RV, Janzen A, Meles SK, et al; REMPET Working Group. 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;36:230-5.
106. Meles SK, Renken RJ, Janzen A, et al; REMPET Study Group. The metabolic pattern of idiopathic REM sleep behavior disorder reflects early-stage Parkinson disease. J Nucl Med. 2018;59:1437-44.