Stage-specific polysomnographic and MRI markers across phenoconversion in isolated REM sleep behavior disorder

Abstract

ObjectivesTo identify stage-specific neurophysiological and structural markers across non-converted isolated rapid eye movement (REM) sleep behavior disorder (iRBD), phenoconverted iRBD, and established alpha-synucleinopathy.MethodsWe retrospectively analyzed 86 patients who underwent video-polysomnography (PSG) and magnetic resonance imaging (MRI), classified at baseline as iRBD or established alpha-synucleinopathy, with longitudinal follow-up to define non-converted (n = 27), phenoconverted iRBD (n = 25), alongside established alpha-synucleinopathy (n = 34). Pairwise comparisons assessed stage-specific differences, followed by multivariable logistic regression to identify discriminative features. Trend analyses and Cox models evaluated progressive changes and predictors of phenoconversion.ResultsCompared with non-converters, phenoconverted iRBD showed PSG abnormalities, including higher NREM arousal and periodic limb movements and lower REM-apnea-hypopnea index (AHI), without structural differences. In contrast, alpha-synucleinopathy showed widespread cortical and limbic atrophy with PSG abnormalities, including reduced N2 sleep and elevated NREM arousal index and heart rate. Logistic regression identified higher NREM arousal index (odds ratio [OR] = 1.08, p = 0.005) and lower REM-AHI (OR = 0.94, p = 0.006) as predictors of phenoconversion. alpha-Synucleinopathy was distinguished from non-converters by left cingulate and hippocampal atrophy, reduced REM-AHI, and elevated NREM heart rate. Trend analyses demonstrated progressive cortical and limbic atrophy from non-converted iRBD to phenoconverted iRBD and established alpha-synucleinopathy. In Cox models, lower left cingulate cortex volume (hazard ratio [HR] = 0.77 per IQR, p = 0.018) and higher NREM arousal index (HR = 1.03, p = 0.010) predicted shorter time to phenoconversion.ConclusionsPSG and MRI capture distinct but complementary, stage-dependent processes in iRBD, with PSG reflecting early functional alterations and MRI indexing progressive neurodegeneration, supporting a stage-aware multimodal approach to risk stratification for alpha-synucleinopathy.