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Semin Neurol 2025; 45(03): 348-357
DOI: 10.1055/a-2544-1482
Review Article

Sleep and Prodromal Synucleinopathies

Johnson D. Pounders
1   Mayo Clinic Department of Neurology, Division of Behavioral Neurology Rochester, Minnesota
,
Stuart J. McCarter
1   Mayo Clinic Department of Neurology, Division of Behavioral Neurology Rochester, Minnesota
2   Mayo Clinic Center for Sleep Medicine, Division of Pulmonology, Rochester, Minnesota
› Author Affiliations
Funding This work was supported by the NIH P30-AG062677.
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Abstract

α-synucleinopathies are a complex group of progressive neurodegenerative disorders with an increasingly recognized long prodromal period, during which sleep dysfunction is a hallmark. Sleep disorders during the prodromal synucleinopathy period, primarily isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and daytime hypersomnolence correlate best with the recently proposed “body-first” Lewy body disease progression. iRBD is the most widely recognized form of prodromal α-synucleinopathy, and patients with iRBD show abnormal α-synuclein in tissues and biofluids even in the absence of cognitive or motor symptoms. More importantly, individuals with iRBD have an elevated risk for near-term development of a clinically diagnosable symptomatic synucleinopathy. Other sleep disorders such as hypersomnia and circadian rhythm dysfunction also occur across the synucleinopathy spectrum, although their prognostic significance is less well understood than iRBD. Finally, isolated REM sleep without atonia may represent an even earlier stage of prodromal synucleinopathy, but further studies are needed.

Keywords

prodromal - synucleinopathy - REM sleep behavior disorder - Circadian Rhythm


Publication History

Article published online:
17 March 2025

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