EEG slow waves and cognitive decline in Isolated Rapid Eye Movements Behavior Disorder: A multicenter longitudinal study

This multicenter retrospective longitudinal study aims to evaluate the association between electroencephalographic slow oscillations (0.3–1 Hz) and slow waves (1–4 Hz) with cognitive performance, and their impact on phenoconversion in patients affected by isolated rapid eye movement (REM) sleep behavior disorder (iRBD). 69 iRBD patients underwent baseline overnight video-polysomnography, clinical assessment, and a neuropsychological evaluation. Phenoconversion was assessed with a follow-up clinical evaluation. Automatic detection of slow oscillations and slow waves was performed during non-REM sleep stage 2 (N2) and 3 (N3) on frontal and central derivations. Clinical, neuropsychological and electrophysiological measures were compared between converters and non-converters. Correlations were computed between cognitive performance and slow oscillations and slow wave densities, as well as between N2 slow oscillation density and N3 slow/fast wave densities. Time-to-event analyses, including Kaplan-Meier and Cox proportional hazards model were performed to assess phenoconversion risk and potential predictors. 30.36 % of patients phenoconverted to an overt alpha-synucleinopathy with a mean follow-up of 45.57 ± 37.26 months. Both slow wave and slow oscillation densities were significantly associated with cognitive performance. Moreover, slow oscillation density in N2 positively correlated with slow oscillation and slow wave density in N3. At baseline, patients who phenoconverted at follow-up showed significantly lower executive function performance and reduced N2 slow oscillation density. In the Cox model including covariates, only executive functions remained a significant predictor. Baseline differences in executive functions may help identify iRBD patients at greater risk of phenoconversion, whereas reduced N2 slow oscillation density may reflect early neurophysiological alterations preceding overt disease.