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

Introduction: REM sleep Behavior Disorder (RBD) represents a strongprodromal marker of a-synucleinopathies. Albeit recent findings underlinedthe importance of NREM sleep in protecting the aging brain fromneurodegeneration, only few studies assessed NREM sleep alterations inRBD and their possible role in cognitive decline. The human K-complex(KC) during NREM sleep exhibits alterations in patients with Alzheimer’sdisease, and a recent study highlighted a relation between KC density andcognitive functioning in isolated RBD (iRBD), particularly in specific domainsknown to be relevant in predicting conversion into neurodegenerativedisorders. The aim of the present study was to assess for the first timethe 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 bothgroups, KCs were detected during Stage 2 NREM sleep in frontal (F3, F4),central (C3, C4, Cz), and parietal (P3, P4) derivations. We performed adirect comparison of the KC density between iRBD and HC. Moreover, weassessed the correlation between midline central KC density, Mini-MentalState Examination (MMSE) scores (in the whole iRBD+HC sample) andperformance in specific neuropsychological measures (in the iRBD group).Results: iRBD patients exhibited a drastic reduction of KC densitycompared to HC in frontal, central, and parietal derivations. The midlinecentral KC density in the whole sample was positively associated withMMSE scores. Finally, the midline central KC density in the iRBD group wasalso selectively and positively associated with performance in attentionand executive functions (i.e., attentional matrices; Raven Colored ProgressiveMatrices).Conclusions: our results describe for the first time a clear reduction of theKC density in iRBD patients compared to HC. Moreover, we confirmed therelation between KC density and cognitive functioning, particularly inspecific domains considered relevant for the prediction of conversion intoa-synucleinopathies. These findings highlight the need of a further understandingof NREM sleep alterations (and particularly KC features) iniRBD, and their possible role in neurodegenerative processes.