MINI REVIEW article
Front. Neurosci.
Sec. Sleep and Circadian Rhythms
This article is part of the Research TopicExploring Circadian Rhythms and Sleep in NeurodegenerationView all 3 articles
Circadian and sleep-wake rhythm alterations in isolated REM sleep behavior disorder: biomarkers of prodromal α-synucleinopathy
Provisionally accepted
- 1Sapienza University of Rome, Rome, Italy
- 2Universita degli Studi di Roma Tor Vergata, Rome, Italy
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Growing evidence highlights a tight interplay linking circadian and sleep–wake disturbances to the pathophysiology of neurodegenerative disorders. In α-synucleinopathies, three key points have emerged: (1) circadian and sleep–wake disruptions may increase the risk of neurodegeneration; (2) these alterations reflect widespread dysfunction in neural circuits regulating sleep, wakefulness, and biological rhythms; and (3) the prodromal condition of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) offers a unique window into early pathological changes, as it is characterized by neurodegeneration in brainstem structures critical for sleep–wake regulation and REM sleep control. Hence, sleep-and circadian-related biomarkers may represent feasible tools for early diagnosis, prevention, and treatment across the spectrum of α-synucleinopathies. However, despite their potential, diagnostic or therapeutic pathways grounded in sleep and circadian biology have yet to be systematically explored or validated, and key questions remain, including the trajectories that characterize the clinical progression from iRBD to overt α-synucleinopathies. Key challenges include translational barriers, inter-individual variability in biomarker profiles, and the need for longitudinal studies to define clinically actionable thresholds. Against this backdrop, this mini-review synthesizes current evidence on sleep–wake rhythm alterations in iRBD as a prodromal stage of α-synucleinopathy-driven neurodegeneration. Candidate circadian biomarkers are discussed, including objective parameters from long-term actigraphic monitoring, encompassing rest–activity rhythms modeled with parametric and non-parametric
Keywords: biomarkers, circadianrhythms, isolated REM sleep behavior disorder (iRBD), Melatonin, Rest–activity rhythms, α-synucleinopathies
Received: 18 Oct 2025; Accepted: 01 Dec 2025.
Copyright: © 2025 Carpi and Liguori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Claudio Liguori
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