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Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies

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Abstract

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = –0.69), memory (RE model = –0.64), and executive function (RE model = –0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. “Vita-Salute” San Raffaele University, Milan, Italy

    Caterina Leitner, Giada D’Este, Marco Sforza, Luigi Ferini-Strambi & Andrea Galbiati

  2. Department of Clinical Neurosciences, Neurology – Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Via Stamira d’Ancona, 20, 20127, Milan, Italy

    Caterina Leitner, Giada D’Este, Samantha Mombelli, Marco Sforza, Francesca Casoni, Marco Zucconi, Luigi Ferini-Strambi & Andrea Galbiati

  3. Comparative Bioacoustics Group, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands

    Laura Verga

  4. Faculty of Psychology and Neuroscience, Department NP&PP, Maastricht University, Maastricht, The Netherlands

    Laura Verga

  5. The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, QC, Canada

    Shady Rahayel

  6. Center for Advanced Research in Sleep Medicine, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord‐de‐l’Île‐de‐Montréal – Hôpital du Sacré‐Cœur de Montréal, Montréal, QC, Canada

    Shady Rahayel

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Contributions

Andrea Galbiati devised and directed the study. Material preparation, data collection and analysis were performed by Caterina Leitner and Giada D’Este. Laura Verga and Shady Rahayel contributed to the interpretation of the results. The first draft of the manuscript was written by Caterina Leitner with support from Andrea Galbiati and Giada D’Este. All authors commented on previous versions of the manuscript, provided critical feedback, and helped shape the research. Finally, all authors read and approved the final manuscript.

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Leitner, C., D’Este, G., Verga, L. et al. Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies. Neuropsychol Rev 34, 41–66 (2024). https://doi.org/10.1007/s11065-022-09572-1

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