In Search of Sleep Biomarkers of Alzheimer's Disease: K-Complexes Do Not Discriminate between Patients with Mild Cognitive Impairment and Healthy Controls.

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

doi:10.3390/brainsci7050051

Abstract

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer’s disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioration.

Highlights

It is well known that Alzheimer’s disease (AD), the most frequent age-related neurodegenerative disorder [1,2], is characterized by several sleep changes [3] associated with cognitive decline: neural degeneration can induce these sleep alterations, which in turn may provoke a worsening of theBrain Sci. 2017, 7, 51; doi:10.3390/brainsci7050051 www.mdpi.com/journal/brainsciBrain Sci. 2017, 7, 51 cognitive decline, e.g., by the impairment of sleep-dependent memory processes [4]
Our findings suggest that no KC density alteration characterizes the sleep of mild cognitive impairment (MCI) patients
KC density is positively associated with Mini-Mental State Examination (MMSE) scores, suggesting a role of KC alterations in the process of cognitive decline

Summary

Introduction

Brain Sci. 2017, 7, 51 cognitive decline, e.g., by the impairment of sleep-dependent memory processes [4]. Activity (SWA) generation, and an impairment of overnight memory consolidation in a sample of healthy older adults. Given this bidirectional influence between sleep disturbances and AD symptoms, the identification of sleep changes in mild cognitive impairment (MCI) [7,8,9], a clinical condition which is considered a possible transitional stage between normal cognitive function and probable AD [2], could be a relevant line of research. Converging evidence in animals and humans points to a cortical origin of the KCs [17,18,19,20], while the thalamus seems to have a role in mediating the cortically generated KCs [18,21]

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