Alterations of the human K-complexes during NREM sleep in isolated REM sleep behaviour disorder

Introduction: REM sleep Behavior Disorder (RBD) represents a strong prodromal marker of a-synucleinopathies. Albeit recent findings underlined the importance of NREM sleep in protecting the aging brain from neurodegeneration, only few studies assessed NREM sleep alterations in RBD and their possible role in cognitive decline. The human K-complex (KC) during NREM sleep exhibits alterations in patients with Alzheimer’s disease, and a recent study highlighted a relation between KC density and cognitive functioning in isolated RBD (iRBD), particularly in specific domains known to be relevant in predicting conversion into neurodegenerative disorders. The aim of the present study was to assess for the first time the existence of KC alterations in iRBD compared to healthy controls (HC). Materials and Methods: we assessed KC density in 31 patients with iRBD (27 M; age: 68.64±6.67 y) and 31 HC (23 M; age: 69.03±6.12 y). In both groups, KCs were detected during Stage 2 NREM sleep in frontal (F3, F4), central (C3, C4, Cz), and parietal (P3, P4) derivations. We performed a direct comparison of the KC density between iRBD and HC. Moreover, we assessed the correlation between midline central KC density, Mini-Mental State Examination (MMSE) scores (in the whole iRBD+HC sample) and performance in specific neuropsychological measures (in the iRBD group). Results: iRBD patients exhibited a drastic reduction of KC density compared to HC in frontal, central, and parietal derivations. The midline central KC density in the whole sample was positively associated with MMSE scores. Finally, the midline central KC density in the iRBD group was also selectively and positively associated with performance in attention and executive functions (i.e., attentional matrices; Raven Colored Progressive Matrices). Conclusions: our results describe for the first time a clear reduction of the KC density in iRBD patients compared to HC. Moreover, we confirmed the relation between KC density and cognitive functioning, particularly in specific domains considered relevant for the prediction of conversion into a-synucleinopathies. These findings highlight the need of a further understanding of NREM sleep alterations (and particularly KC features) in iRBD, and their possible role in neurodegenerative processes.