The Fall of Sleep K-Complex in Alzheimer Disease

Luigi De Gennaro,Paolo Maria Rossini,Giulia Lauri,Anastasia Mangiaruga,Serena Scarpelli,Maurizio Gorgoni,Camillo Marra,Ilaria Truglia,Flaminia Reda,Giordano Lacidogna,Aurora D’Atri,Susanna Cordone,Michele Ferrara

doi:10.1038/srep39688

Abstract

Although a slowing of electroencephalographic (EEG) activity during wakefulness and –to some extent- sleep of Alzheimer disease (AD) patients (i.e., increased slow-frequency activity) was documented, recent findings in healthy elderly show a decreased 0.6–1 Hz slow wave activity (SWA) during NREM, which was associated to β-amyloid deposition and impaired hippocampal memory consolidation. We hypothesize that the apparent contradiction may be explained by the partial overlap between 0.6–1 Hz EEG activity and K-Complex (KC). According to this view, we studied both frontal KCs and SWA in 20 AD patients and 20 healthy age-matched controls (HC) during nightly sleep, under the hypothesis that KCs better discriminate patients from healthy elderly than ≤1 Hz SWA. A drastic decrease of KC density during stage 2 NREM was found in AD compared to HC. Patients show more than 40% reduction of the KC density, allowing a correct classification of 80%. On the other hand, ≤1 Hz SWA of AD patients is slightly (not significantly) higher in most cortical areas compared to HC. Although no significant changes of ≤1 Hz SWA are detectable over frontal areas in AD, KC density decreases over the same location, and its decrease is related to the cognitive decline.

Highlights

Alzheimer’s disease (AD) is characterized by several sleep alterations accompanying cognitive decline: the neural degeneration can induce per se alterations of sleep pattern and quality, which in turn may provoke a worsening of the cognitive decline, i.e. by the impairment of sleep-dependent memory consolidation processes[1]
We hypothesize that these findings do not necessarily contradict the phenomenon of EEG slowing in AD patients, and that the
Our results show a striking decrease of frontal spontaneous KC density during NREM sleep in AD patients compared to healthy elderly control subjects (HC)

Summary

Introduction

Alzheimer’s disease (AD) is characterized by several sleep alterations accompanying cognitive decline: the neural degeneration can induce per se alterations of sleep pattern and quality, which in turn may provoke a worsening of the cognitive decline, i.e. by the impairment of sleep-dependent memory consolidation processes[1]. Contradictory, a recent study showed in healthy subjects that the β-amyloid deposition is associated with an impaired frontal generation of NREM slow-wave activity (0.6–1 Hz) that, in turn, predicts hindered hippocampal memory consolidation[9]. The same group demonstrated that age-related NREM slow-wave activity mediates the relation between prefrontal grey matter atrophy and impaired long-term memory and reduced hippocampal-prefrontal functional connectivity[10]. We hypothesize that these findings do not necessarily contradict the phenomenon of EEG slowing in AD patients, and that the

Methods

Discussion

Conclusion