Disfunzione del sistema glinfatico nei pazienti con disturbo comportamentale del sonno REM: studio di neuroimaging
Glymphatic system dysfunction in REM sleep behavior disorder patients: a neuroimaging study
Autori
Grassi Andrea – [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Vita-Salute San Raffaele University, Milan, Italy]
Basaia Silvia – [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy]
Sarasso Elisabetta – [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Vita-Salute San Raffaele University, Milan, Italy; and Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genoa, Genoa, Italy]
Gardoni Andrea -[Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; and Vita-Salute San Raffaele University, Milan, Italy]
Marelli Sara – [Division of Neuroscience, Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy]
Balestrino Roberta -[Neurology Unit, and Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy]
Zenere Lucia – [Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy]
Castelnuovo Alessandra – [Division of Neuroscience, Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy]
Ferini-Strambi Luigi – [Vita-Salute San Raffaele University, Milan, Italy; and Division of Neuroscience, Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy]
Filippi Massimo – [Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy] Agosta Federica – [Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy]
Introduction
Impairment of brain glymphatic function might play a role in the onset of α-synucleinopathies. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) is a non-invasive method that has been recently proposed for evaluating glymphatic system function. This study aimed to use DTI-ALPS to evaluate glymphatic system activity in patients with isolated rapid eye movement sleep behavior disorder (iRBD) that represents a prodromal condition for the development of neurodegenerative parkinsonism.
Methods
Thirty-eight patients with a polysomnography-confirmed iRBD and 36 age- and sex-matched controls were enrolled and underwent a brain MRI scan including DTI and susceptibility map-weighted imaging sequences. DTI-ALPS index from each individual was calculated by a ratio of the diffusivities along the x-axis in the projection and association neural fibers to the diffusivities perpendicular to them and compared between groups using ANCOVA models, age- and sex-adjusted. Correlations with clinical and cognitive measures were tested. The percentage risk of conversion to α-synucleinopathies in iRBD patients was evaluated using the most important predictors of progression (UPDRS-III scores, autonomic scales, cognitive dysfunction, hyposmia, and genetic mutations).
Results
Sixteen patients are likely to convert (c-iRBD), while 19 are not (nc-iRBD). c-iRBD have higher age, Beck’s Depression Inventory and Epworth Sleepiness Scale scores relative to nc-iRBD group. There are no differences in disease duration (DD) and UPDRS-III between the two groups of patients. c-iRBD presented a higher probability of conversion relative to nc-iRBD (95% vs 36%), with the probability of conversion being higher in subjects with a higher UPDRS-III score. iRBD patients exhibited lower mean DTI-ALPS index than controls (1.30 vs 1.55; P = 0.03). Moreover, DTI-ALPS index was lower in iRBD with DD greater than 5 years relative to controls (P=0.043), while iRBD with DD equal to 5 did not show any significant differences than controls. The DTI-ALPS index and DD were negatively correlated in iRBD patients.
Discussion and Conclusion
The findings indicate significant differences in clinical parameters between iRBD and controls and c-iRBD and nc-iRBD patients. The lack of difference in UPDRS-III scores highlights the complexity of disease mechanisms not captured by motor symptoms alone. We confirmed the presence of altered glymphatic function in iRBD patients, with greatest damage in patients with longer DD.
Age, depression, and sleepiness might be key predictors of conversion in iRBD patients, with the DTI-ALPS index serving as a promising biomarker for disease progression.
Supported by. Italian Ministry of Health [grant number #RF-2018-12366746]
REFERENCES
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