Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder

Abstract

This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P < 0.000001), constipation, (P < 0.000001) and age over 70 years (P = 0.0002). Combined features obtained from the generalized logistic regression achieved a hazard ratio of 5.71 (95% confidence interval 2.85–11.43). Bayesian classifier suggested that patients with higher Mini-Mental State Examination score and lower caudate SBR asymmetry were more likely to develop parkinsonism, while patients with the opposite pattern were more likely to develop dementia. This study shows that iRBD patients older than 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.

Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review

“…Additionally, a progressive decline in striatal binding in patients with iRBD further support the notion that RBD is actually an integral prodromal period of a defined neurodegenerative syndrome [ 182 ]. Several recent studies confirmed the high sensitivity of abnormal DAT-SPECT to accurately predict the short-term conversion to a clinically-defined α-synucleinopathy [ 183 , 184 , 185 , 186 , 187 ].…”

Phase and amplitude electroencephalography correlations change with disease progression in people with idiopathic rapid eye-movement sleep behavior disorder

“…Rapid eye-movement sleep behavior disorder (RBD) is a parasomnia disorder that involves violent and undesirable behaviors [ 1 ] such as physical reactions to dreams due to the loss of normal muscle atonia during rapid eye movement (REM) sleep. RBD can occur alone (idiopathic RBD—iRBD) or in association with other neurological disorders (symptomatic RBD) [ 2 ], and people with iRBD have a high risk of developing Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple systemic atrophy [ 3 , 4 ].…”

Cardiac Autonomic Dysfunction Is Associated with Severity of REM Sleep without Atonia in Isolated REM Sleep Behavior Disorder

“…Accordingly, recent studies have suggested that 'isolated RBD (iRBD)' reflects the early phase of later development of neurodegenerative changes, as the concept of 'prodromal parkinsonism' has been suggested to represent an early expression of α-synucleinopathy [7]. According to the results of recently published prospective studies, the phenoconversion rate from iRBD to parkinsonism or dementia are similar [8,9].…”