Rapid Eye Movements (REMs) during Non‐REM Sleep as a Marker of Alpha‐Synucleinopathies

Abstract Background Alpha‐synuclein‐related neurodegeneration affects sleep figures, whether in the prodromal (rapid eye movement [REM] sleep behavior disorder, iRBD) or established (Parkinson's disease [PD] and multiple system atrophy [MSA]) stages. Objective To look for abnormal intrusions of REMs in non‐REM sleep in alpha‐synucleinopathies. Methods Clinical measures and polysomnography were collected from 554 participants with PD (N = 257), iRBD (N = 110), and MSA (N = 71) and 115 controls. Initially, the polysomnography was visually examined for REMs in N2 (presence and index). Subsequently, REMs were automatically detected in all wake and sleep stages, and thresholds discriminating between the disorders were sought. Results The REMs index in N2 (visually measured) was lower in controls than all patients groups. The REMs index in N2 (automatically measured) was lower in controls than in patients with PD and MSA, but not different from iRBD participants. The optimal cutoff of 4.6 REMs/h of N2 yielded a 77% specificity to discriminate controls from all neurodegenerative groups but sensitivity was 60%. The cutoff to discriminate MSA from PD participants had a low specificity (58%). The optimal cutoff of 2.1/h in iRBD patients had an 80% specificity for distinguishing them from controls. Conclusions Abnormal intrusion of REMs into non‐REM sleep distinguishes participants with alpha‐synucleinopathies from controls. This automated technique could be used to identify patients with neurodegenerative disorders in the large number of polysomnograms obtained for other purposes in the elderly. © 2025 International Parkinson and Movement Disorder Society.