Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Abstract

Background: Excessive aggregation of α-synuclein is the key pathophysiological feature of Parkinson's disease (PD). Rapid eye movement sleep behavior disorder (RBD) is also associated with synucleinopathies and considered as a powerful predictor of PD. Growing evidence suggests the diminished clearance of α-synuclein may be partly attributable to poor interstitial fluid drainage, which can be reflected by magnetic resonance imaging (MRI)-visible enlarged perivascular space (EPVS). However, the effect of MRI-visible EPVS on iRBD and PD, and their correlation with clinical characteristics remain unclear. Objective: To evaluate the clinical and neuroimaging significance of MRI-visible EPVS in iRBD and PD patients. Methods: We enrolled 33 iRBD patients, 82 PD (with and without RBD) patients, and 35 healthy controls (HCs), who underwent clinical evaluation and 3.0 Tesla MRI. Two neurologists assessed MRI-visible EPVS in centrum semiovale (CSO), basal ganglia (BG), substantia nigra (SN), and brainstem (BS). Independent risk factors for iRBD and PD were investigated using multivariable logistic regression analysis. Spearman analysis was used to test the correlation of MRI-visible EPVS with clinical characteristics of patients. Results: iRBD patients had significantly higher EPVS burdens (CSO, BG, SN, and BS) than PD patients. Higher CSO-EPVS and BS-EPVS burdens were independent risk factors for iRBD. Furthermore, higher CSO-EPVS and SN-EPVS burdens were positively correlated with the severity of clinical symptom in iRBD patients, and higher BG-EPVS burden was positively correlated with the severity of cognitive impairment in PD patients. Conclusion: iRBD and PD patients have different MRI-visible EPVS burdens, which may be related with a compensatory mechanism in glymphatic system. Lower MRI-visible EPVS burden in PD patients may be a manifestation of severe brain waste drainage dysfunction. These findings shed light on the pathophysiologic relationship between iRBD and PD with respect to neuroimaging marker of PD.

Sleep and perivascular spaces in the middle‐aged and elderly population

“…Our population‐based findings seem inconsistent with previous clinical studies in patients with sleep or neurological disorders, that predominantly report an association of poor sleep across different characteristics with higher PVS load (Berezuk et al, 2015; Opel et al, 2019; Si et al, 2020; Song et al, 2017; Wang et al, 2020). Noteworthy, two studies from one population‐based cohort also mostly reported null findings (Del Brutto et al, 2019, 2020).…”

Glymphatic dysfunction in isolated REM sleep behavior disorder

“…In a recent MRI study, patients with iRBD showed significantly higher enlarged perivascular space burdens than those with PD. As the disease progressed, poor perivascular space drainage caused increased deposition of metabolites and α‐synuclein aggregation, which may obstruct the perivascular drainage systems 20 18 .…”

“…Patients with iRBD, especially men aged >50 years, will show conversion to α‐synucleinopathy disease, with a mean interval for conversion from the time of RBD onset being ~10 years, and the average annual risk of neurodegeneration being 8% 16,18,19 . Recent study also suggested that sleep disruption during REM sleep and neuroinflammation may lead to increased metabolite deposition and α‐synucleinopathy aggregation 20 …”

Neurochemical Features of Rem Sleep Behaviour Disorder

“…The results of studies assessing structural and functional MRI (fMRI) studies are summarized, in chronological order, in Table 4 [ 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 ]. These include sudies of gray matter volume (GMV), cortical thickness, diffusion tensor imaging, dorsal nigral hyperintensity (DNH), neuromelanin-sensitive structural and diffusion MRI, and functional MRI.…”

“…A recent study described higher burdens of EPVS in the centrum semiovale, basal ganglia, substantia nigra, and brainstem of iRBD patients in comparison with PD patients and controls, being higher EPVS in the centrum semiovale and the brainstem as independent risk factors for iRBD [ 185 ].…”