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Background And Objectives: Cognitive impairments are common in idiopathic REM sleep behavior disorder (iRBD), in which the cholinergic degeneration of nucleus basalis of Meynert (NBM) may play an important role. However, the progressive changes of NBM, the relationship between progressive NBM degeneration and progression of cognitive impairments, and whether degeneration of the NBM can predict cognitive decline in patients with iRBD remain unclear. This study aimed to investigate the cross-sectional and longitudinal microstructural alterations in the NBM of patients with iRBD using free-water imaging and whether free water in the NBM is related to cognitive, mood, and autonomic function.
Methods: We compared the baseline free-water values in the NBM between 59 healthy controls (HCs), 57 patients with iRBD, 57 patients with Parkinson disease (PD) with normal cognition (PD-NC), and 64 patients with PD with cognitive impairment (PD-CI). Thirty patients with iRBD and 40 HCs had one longitudinal data. In patients with iRBD, we explored the associations between baseline and longitudinal changes of free-water values in the NBM and clinical characteristics and whether baseline free-water values in the NBM could predict cognitive decline.
Results: IRBD, PD-NC, and PD-CI groups had significantly increased free-water values in the NBM compared with HCs, whereas PD-CI had higher free-water values compared with iRBD and PD-NC. In patients with iRBD, free-water values in the NBM were progressively elevated over follow-up and correlated with the progression of cognitive impairment and depression. Free-water values in the NBM could predict cognitive decline in the iRBD group. Furthermore, we found that patients with iRBD with cognitive impairment had higher relative change of free-water value in the NBM compared with patients with iRBD with normal cognition over follow-up.
Discussion: This study proves that free-water values in the NBM are elevated cross-sectionally and longitudinally and are associated with the progression of cognitive impairment and depression in patients with iRBD. Moreover, the free-water value in the NBM can predict cognitive decline in patients with iRBD. Whether free-water imaging of the NBM has the potential to be a marker for monitoring progressive cognitive impairment and predicting the conversion to dementia in synucleinopathies needs further investigation.
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http://dx.doi.org/10.1212/WNL.0000000000209220 | DOI Listing |
Biomed Eng Lett
September 2025
Department of Biomedical Engineering, College of Health Science, Yonsei University, Wonju, South Korea.
Unlabelled: Purpose: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a sleep disorder considered to be a prodromal stage of neurodegeneration disease and is often accompanied by cognitive impairments. The purpose of this study was to investigate spatiotemporal characteristics of abnormal oscillatory cortical activity associated with dysfunction of visuospatial attention in iRBD based on an explainable machine learning approach. Methods: EEGs were recorded from 49 iRBD patients and 49 normal controls while they were performing Posner's cueing task and transformed to cortical current density time-series.
View Article and Find Full Text PDFSleep Med Clin
September 2025
Centre for Neurology, Academic Specialist Centre, Stockholm Health Services, Solnavägen 2, 11365 Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Neurology, Karolinska University Hospital, Bioclinicum J5:20, Stockholm 17164, Swede
Parkinson's disease is a neurodegenerative disorder with an increasing prevalence worldwide. The development of disease-modifying therapies remains a critical priority; however, early intervention is limited by the paucity of robust biomarkers for the prodromal stage. Sleep disturbances-particularly isolated rapid eye movement sleep behavior disorder (iRBD)-are emerging as key clinical markers of prodromal synucleinopathy, offering opportunities for early detection and risk stratification.
View Article and Find Full Text PDFMov Disord
September 2025
Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Background: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal manifestation of synucleinopathies and provides a critical window to identify early markers of progression to Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Time-averaged (static) and time-varying (dynamic) functional connectivity between large-scale brain networks may sensitively capture early pathophysiological changes and offer prognostic value beyond structural imaging.
Objectives: To use functional magnetic resonance imaging (fMRI) on a longitudinal iRBD cohort to assess alterations in static and dynamic functional connectivity and explore their relationship with disease conversion and regional neurotransmitter density.
J Parkinsons Dis
September 2025
Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada.
Individuals with isolated REM sleep behavior disorder (iRBD) are at high risk of developing α-synucleinopathies, particularly Parkinson's disease (PD) and dementia with Lewy bodies (DLB). With the development of potential neuroprotective treatments for synucleinopathies, including PD, identifying clinical features that can allow for tracking subtle changes in prodromal disease and thereby monitoring risk of phenoconversion in iRBD is paramount. Subtle motor deficits have been suggested to be present in iRBD, making them potentially important clinical markers for predicting future phenoconversion.
View Article and Find Full Text PDFMov Disord Clin Pract
July 2025
Centre for Preventive Neurology, Charterhouse Square, Queen Mary University of London, London, UK.
Background: Isolated RBD (iRBD) is a prominent early marker of Parkinson's disease and related disorders.
Objectives: Evaluate biomarkers of inflammation and axonal damage people with iRBD for disease progression.
Methods: Plasma samples from 27 video-polysomnography confirmed iRBD patients and 25 controls were analyzed for inflammatory biomarkers (CRP, IL-6, TNF-α, IFN-γ, IL-1β) and NfL using the Meso Scale Discovery platform.