ArticleNeurology2025
Association of Cardiovascular Autonomic Failure With Progression and Phenoconversion in Isolated REM Sleep Behavior Disorder.
Article in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Impaired Dynamic Cerebral Autoregulation Across the REM Sleep Behavior Disorder Spectrum: Evidence From Isolated REM Sleep Without Atonia to Parkinson's Disease With RBD.CNS neuroscience & therapeutics · 2026Observational
- Utility and best practices for clinical diagnostic testing of the autonomic nervous system: A Consensus Statement Endorsed by the American Autonomic Society and the American Association of Neuromuscular & Electrodiagnostic Medicine.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Review
- Early Autonomic Burden in Prodromal Parkinson's Disease Predicts Cognitive Impairment.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- REM Sleep Behavior Disorder as a Prodromal Synucleinopathy: Updates on Clinical and Laboratory Biomarkers, and Implications for Neuroprotective Trials.Current neurology and neuroscience reports · 2025Review
- Article
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13 authors.
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Abstract
BACKGROUND AND
objectivesIsolated REM sleep behavior disorder (iRBD) is a prodromal state of α-synucleinopathies, presenting years before overt neurodegenerative disorders. Autonomic nervous system (ANS) involvement, particularly cardiovascular autonomic failure, may indicate progression. However, its role as a (multidimensional) marker for disease progression and phenoconversion remains unclear. This study aimed to investigate whether cardiovascular autonomic failure and symptoms of autonomic dysfunction serve as multidimensional markers in patients with iRBD.
methodsWe conducted a prospective cohort study of patients with iRBD (iRBDs) and controls. Participants underwent cardiovascular reflex tests (CRTs) with beat-to-beat monitoring of blood pressure (BP) and ANS symptom assessments at baseline and annually. Primary outcomes were prevalence and progression of cardiovascular autonomic failure and the risk factors of phenoconversion. Longitudinal changes were evaluated through mixed-effects regression, predictors associated with conversion with Cox regression analysis.
resultsSixty-four iRBDs (mean age 68.89 ± 6.75 years, 75% male) and 67 controls (66.57 ± 7.91 years, 68% male) were recruited. At baseline, iRBDs exhibited a prevalent sympathetic cardiovascular dysfunction, with more frequent neurogenic orthostatic hypotension (nOH in 9 iRBDs) and abnormal BP responses to CRTs (pathologic Valsalva maneuver [VM] overshoot in 27 iRBDs). Longitudinal data demonstrated progressive deterioration of sympathetic baroreflex function, with increased prevalence of nOH (7 iRBDs with incident nOH; yearly odds ratio [OR] = 2.44) and deterioration of parasympathetic cardiovagal function. Thirteen patients (20.3%) phenoconverted to α-synucleinopathies. Neurogenic OH (hazard ratio [HR] = 5.05), altered sympathetic baroreflex function (pathologic VM HR = 3.49), and blunted parasympathetic cardiovagal responses (pathologic deep breathing heart rate ratio HR = 3.27) were significant risk factors for phenoconversion; their early appearance 5 years from iRBD onset increased the conversion risk, up to 4-fold. Symptoms of autonomic failure were more prevalent in iRBD and deteriorated over time but failed to predict conversion. DISCUSSION: Progressive deterioration of cardiovascular autonomic function is a feature of iRBDs and affects the risk of phenoconversion. Limitations include the relatively short follow-up period and small number of converters. This study highlights the importance of objective cardiovascular autonomic testing as a multidimensional marker for risk stratification in iRBD.
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