Neuropsychological, electrophysiological, and neuroimaging biomarkers for REM behavior disorder

ABSTRACT

Introduction: Rapid eye movement (REM) sleep behavior disorder (RBD) is a REM sleep parasomnia characterized by dream enacting behaviors allowed by the loss of physiological atonia during REM sleep. This disorder is recognized as a prodromal stage of neurodegenerative disease, in particular Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). Therefore, a timely identification of biomarkers able to predict an early conversion into neurodegeneration is of utmost importance.

Areas covered: In this review, the authors provide updated evidence regarding the presence of neuropsychological, electrophysiological and neuroimaging markers in isolated RBD (iRBD) patients when the neurodegeneration is yet to come.

Expert opinion: Cognitive profile of iRBD patients is characterized by the presence of impairment in visuospatial abilities and executive function that is observed in α-synucleinopathies. However, longitudinal studies showed that impaired executive functions, rather than visuospatial abilities, augmented conversion risk. Cortical slowdown during wake and REM sleep suggest the presence of an ongoing neurodegenerative process paralleled by cognitive decline. Neuroimaging findings showed that impairment nigrostriatal dopaminergic system might be a good marker to identify those patients at higher risk of short-term conversion. Although a growing body of evidence the identification of biomarkers still represents a critical issue in iRBD.

KEYWORDS:

• REM sleep behavior disorder
• biomarkers
• cognitive function
• EEG
• neuroimaging
• neuropsychology

Article highlights

• RBD is a REM sleep parasomnia characterized by dream enacting behaviors allowed by the loss of physiological atonia present during REM sleep.

• RBD is classified as iRBD when it occurs in the absence of any other medical conditions, or as secondary when it is caused by the presence of other neurological conditions.

• iRBD is now well recognized as a prodromal stage of neurodegenerative disease, in particular Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB); therefore, there is a need of longitudinal studies aimed to identify reliable biomarker for conversion’s prediction.

• Several studies reported that iRBD patients are characterized by neuropsychological impairments, in particular in executive functions and visuospatial abilities. However, longitudinal findings showed that only impaired executive functions increased the risk for phenoconversion.

• MCI is frequent in iRBD patients with an estimated prevalence between 33% and 50%. Its presence at the baseline is able to identify those patients who firstly converted into dementia.

• iRBD patients are characterized by EEG slowing during wake and during REM sleep that are able to identify those iRBD patients with higher risk of short-term conversion.

• RSWA has been also suggest to be a good marker for phenoconversion. In particular, higher percentage of tonic chin EMG at baseline is predictive of a conversion toward PD.

• Neuroimaging biomarkers strictly related to neuropathological stages of Braak’s Model may be useful to better identify and characterize iRBD subjects converting in a clinical defined neurodegenerative disease such as PD and DLB.

• Neuroimaging signs of nigral damage including dopaminergic denervation are crucial for monitoring the disease progression and prediction the RBD phenoconversion. Furthermore, the use of combined, rather than single neuroimaging biomarkers (extranigral, nigral and cortical damages) represents a novel promising frontier.

• The availability of longitudinal data in neuropsychological, electrophysiological and neuroimaging studies is limited. Furthermore, a clear stratification for biomarkers that should predict patients’ trajectories over time and a clear distinction between different phenoconversion, namely PD, DLB, and MSA, is far from being satisfactory.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.