Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial-ready idiopathic rapid eye movement sleep behavior patients.
Parkinson's disease
REM sleep behavior disorder
dementia
multiple system atrophy
synucleinopathy
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
revised:
18
07
2023
received:
24
05
2023
accepted:
23
07
2023
medline:
10
11
2023
pubmed:
27
7
2023
entrez:
27
7
2023
Statut:
ppublish
Résumé
Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects. Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios. 365 patients were enrolled, and 289 patients with follow-up (age 67.7 ± 7.3 years, 237 males, mean follow-up 40 ± 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project. Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization.
Substances chimiques
Dopamine
VTD58H1Z2X
Types de publication
Multicenter Study
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3703-3710Informations de copyright
© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Références
Arnulf I. REM sleep behavior disorder: motor manifestations and pathophysiology. Mov Disord. 2012;27(6):677-689.
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. doi:10.1016/J.SMRV.2018.09.008
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(9):1872-1876. doi:10.1002/acn3.50833
Doppler K, Antelmi E, Kuzkina A, et al. Consistent skin α-synuclein positivity in REM sleep behavior disorder - a two center two-to-four-year follow-up study. Parkinsonism Relat Disord. 2021;86:108-113. doi:10.1016/J.PARKRELDIS.2021.04.007
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(3):203-212. doi:10.1016/S1474-4422(20)30449-X
Poggiolini I, Gupta V, Lawton M, et al. Diagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies. Brain. 2022;145(2):584-595. doi:10.1093/BRAIN/AWAB431
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(3):744-759. doi:10.1016/j.smrv.2018.09.008
Arnaldi D, Chincarini A, Hu MT, et al. Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder. Brain. 2021;144(1):278-287. doi:10.1093/BRAIN/AWAA365
Elliott JE, Lim MM, Keil AT, et al. Baseline characteristics of the North American Prodromal Synucleinopathy cohort. Ann Clin Transl Neurol. 2023;10:520-535. doi:10.1002/acn3.51738
Puligheddu M, Figorilli M, Antelmi E, et al. Predictive risk factors of phenoconversion in idiopathic REM sleep behavior disorder: the Italian study “FARPRESTO.”. Neurol Sci. 2022;1:1-10. doi:10.1007/S10072-022-06374-4/TABLES/3
American Academy of Sleep Medicine (AASM). International Classification of Sleep Disorders - Third Edition (ICSD-3). American Academy of Sleep Medicine; 2014.
McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies. Neurology. 2017;89(1):88-100.
Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015;30(12):1591-1601. doi:10.1002/mds.26424
Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670-676. doi:10.1212/01.wnl.0000324625.00404.15
Morbelli S, Esposito G, Arbizu J, et al. EANM practice guideline/SNMMI procedure standard for dopaminergic imaging in parkinsonian syndromes 1.0. Eur J Nucl Med Mol Imaging. 2020;47(8):1885-1912. doi:10.1007/s00259-020-04817-8
Fluss R, Faraggi D, Reiser B. Estimation of the Youden index and its associated cutoff point. Biometrical J Math Methods Biosci. 2005;47(4):458-472.
Lang AE, Espay AJ. Disease modification in Parkinson's disease: current approaches, challenges, and future considerations. Mov Disord. 2018;33(5):660-677. doi:10.1002/MDS.27360
Pagano G, Taylor KI, Anzures-Cabrera J, et al. Trial of prasinezumab in early-stage Parkinson's disease. N Engl J Med. 2022;387(5):421-432. doi:10.1056/NEJMOA2202867/SUPPL_FILE/NEJMOA2202867_DATA-SHARING.PDF
Lang AE, Siderowf AD, Macklin EA, et al. Trial of cinpanemab in early Parkinson's disease. N Engl J Med. 2022;387(5):408-420. doi:10.1056/NEJMOA2203395/SUPPL_FILE/NEJMOA2203395_DATA-SHARING.PDF
Arnaldi D, Famà F, Girtler N, et al. Rapid eye movement sleep behavior disorder: a proof-of-concept neuroprotection study for prodromal synucleinopathies. Eur J Neurol. 2021;28(4):1210-1217. doi:10.1111/ENE.14664
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(8):671-684. doi:10.1016/S1474-4422(21)00176-9
Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984;32(3):489-502. doi:10.1016/0031-9384(84)90269-5
Mahlknecht P, Iranzo A, Högl B, et al. Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD. Neurology. 2015;84(7):654-658. doi:10.1212/WNL.0000000000001265