The Fall of Sleep K-Complex in Alzheimer Disease

Gennaro, Luigi De; Gorgoni, Maurizio; Reda, Flaminia; Lauri, G.; Truglia, I.; Cordone, Susanna; Scarpelli, Serena; Mangiaruga, Anastasia; D’Atri, Alessandro; Lacidogna, Giordano; Ferrara, Michele; Marra, Camillo; Rossini, Paolo Maria

doi:10.1038/srep39688

Cited by 88 publications

(83 citation statements)

References 66 publications

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“…Thus, larger slow waves are associated with stronger and faster hemodynamic changes that may lead to a more efficient mobilization of the CSF. This hypothesis would be consistent with previous reports of a direct link between alterations of slow wave activity and cognitive decline related to the accumulation of β-amyloid in the medial prefrontal cortex of older individuals (De Gennaro et al, 2017;Mander et al, 2015).…”

Section: Human Slow Waves Are Coupled With Cortically Propagating Hemsupporting

confidence: 93%

Cortical and subcortical hemodynamic changes during human sleep slow waves

Betta

Handjaras

Leo

et al. 2020

Preprint

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EEG slow waves, the hallmarks of NREM sleep, are closely linked to the restorative function of sleep and their regional cortical distribution reflects plasticity-and learning-related processes. Here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to sleep slow waves. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLDsignal decreases were found in several areas, including insula and somatomotor cortex, and were preceded by slow signal increases that peaked around slow-wave onset. EEG slow waves and BOLD fluctuations showed similar cortical propagation patterns, from centro-frontal to temporo-occipital cortices. These regional patterns of hemodynamic-electrical coupling are consistent with theoretical accounts of the functions of sleep slow waves.

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Section: Human Slow Waves Are Coupled With Cortically Propagating Hemsupporting

confidence: 93%

Cortical and subcortical hemodynamic changes during human sleep slow waves

Betta

Handjaras

Leo

et al. 2020

Preprint

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“…De Gennaro et al. () explained this apparent contradiction by the partial frequency overlap between delta EEG activity and K‐complexes that have been associated with memory consolidation. The K‐complex number and shape are altered in the course of neurodegeneration but seem to be unaltered in earlier stages of cognitive impairment (Reda et al., ).…”

Section: Discussionmentioning

confidence: 99%

Sleep efficiency and neurophysiological patterns in middle‐aged men are associated with cognitive change over their adult life course

Waser

Lauritzen

Fagerlund

et al. 2018

Journal of Sleep Research

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Summary Disrupted sleep is a contributing factor to cognitive ageing, while also being associated with neurodegenerative disorders. Little is known, however, about the relation of sleep and the gradual cognitive changes over the adult life course. Sleep electroencephalogram (EEG) patterns are potential markers of the cognitive progress. To test this hypothesis, we assessed sleep architecture and EEG of 167 men born in the Copenhagen Metropolitan Area in 1953, who, based on individual cognitive testing from early (~18 years) to late adulthood (~58 years), were divided into 85 subjects with negative and 82 with positive cognitive change over their adult life. Participants underwent standard polysomnography, including manual sleep scoring at age ~58 years. Features of sleep macrostructure were combined with a number of EEG features to distinguish between the two groups. EEG rhythmicity was assessed by spectral power analysis in frontal, central and occipital sites. Functional connectivity was measured by inter‐hemispheric EEG coherence. Group differences were assessed by analysis of covariance (p < 0.05), including education and severity of depression as potential covariates. Subjects with cognitive decline exhibited lower sleep efficiency, reduced inter‐hemispheric connectivity during rapid eye movement (REM) sleep, and slower EEG rhythms during stage 2 non‐REM sleep. Individually, none of these tendencies remained significant after multiple test correction; however, by combining them in a machine learning approach, the groups were separated with 72% accuracy (75% sensitivity, 67% specificity). Ongoing medical screenings are required to confirm the potential of sleep efficiency and sleep EEG patterns as signs of individual cognitive progress.

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“…Spatial orientation and navigation involve hippocampal-parietal cortex (PC) interactions (Aguirre and D'Esposito, 1999;Byrne et al, 2007;Clark et al, 2018;Jarrard, 1993;Ji and Wilson, 2006;Kolb et al, 1994;Maingret et al, 2016;McNaughton et al, 1995;Morris et al, 1982;Nitz, 2012;Oess et al, 2017;Pai and Yang, 2013;Rogers and Kesner, 2006;Sherrill et al, 2013;Tu et al, 2017;Whitlock et al, 2012;Wilber et al, 2014;Wilber et al, 2017), and dysfunctional cortical-hippocampal interactions are a prominent feature in AD (Cacucci et al, 2008;Huijbers et al, 2014;Jacobs et al, 2012;Kunz et al, 2015;Morbelli et al, 2012;Mormino et al, 2012;Song et al, 2016;Wang et al, 2013), including abnormal communication between the PC and hippocampus (Jacobs et al, 2012;Kunz et al, 2015;Morbelli et al, 2012;Wang et al, 2013). These findings, make the hippocampal-PC network an ideal model for studying altered hippocampal-cortical interactions in AD (Cacucci et al, 2008;De Gennaro et al, 2017;Huijbers et al, 2014;Mormino et al, 2012;Song et al, 2016) .…”

Section: Introductionmentioning

confidence: 92%

“…For example, the density and amplitude of hippocampal sharp wave ripples (SWRs) are reduced in these models (Ciupek et al, 2015;Gillespie et al, 2016;Witton et al, 2016). Additionally, later in AD progression, both animal models and humans show changes in slow-wave sleep (SWS) (De Gennaro et al, 2017;Mander et al, 2016;Van Erum et al, 2019). Finally, impaired navigation-related learning and memory in AD mice is largely a consequence of forgetting from one day to the next (Billings et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Impaired Hippocampal-cortical interactions during sleep and memory reactivation without consolidation in a mouse model of Alzheimer’s disease

Benthem¹,

Skelin

Moseley³

et al. 2019

Preprint

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Spatial learning is impaired in preclinical Alzheimer's disease (AD). We reported similar impairments in 3xTg-AD mice learning a spatial reorientation task. Memory reactivation during sleep is critical for learning related plasticity, and memory consolidation is correlated with hippocampal sharp wave ripple (SWR) density, cortical delta waves (DWs), and their temporal coupling -postulated as a physiological substrate of memory consolidation. Finally, hippocampal-cortical dyscoordination is prevalent in individuals with AD. Thus, we hypothesized impaired memory consolidation mechanisms in hippocampal-cortical networks could account for spatial memory deficits. We assessed sleep architecture, SWR/DW dynamics and memory reactivation in a mouse model of tauopathy and amyloidosis implanted with a recording array targeting isocortex and hippocampus. Mice underwent daily recording sessions of rest-task-rest while learning the spatial reorientation task. We assessed memory reactivation by matching activity patterns from the approach to the unmarked reward zone to patterns during slow wave sleep (SWS). AD mice had more SWS, but reduced SWR density. The increased SWS compensated for reduced SWR density so there was no reduction in SWR number. Conversely, DW density was not reduced so the number of DWs was increased. In control mice hippocampal SWR-cortical DW coupling was strengthened in post-tasksleep and was correlated with performance on the spatial reorientation task the following day. However, in AD mice SWR-DW coupling was reduced and not correlated with behavior, suggesting behavioral decoupling. Thus, reduced SWR-DW coupling may cause impaired learning in AD and may serve as a biomarker for early AD related changes. Significance StatementUnderstanding the relationship between network dynamics and cognition early in Alzheimer's disease progression is critical for identifying therapeutic targets for earlier treatment. We assessed hippocampal-cortical interactions during sleep in AD mice as a potential cause of early spatial learning and memory deficits. We identified compensatory sleep changes in AD mice, that ameliorated some brain dysfunction. Despite the compensatory changes, impaired spatial navigation and impaired hippocampal-cortical (sharp wave ripple-delta wave) interactions were apparent in AD mice. In control but not AD mice hippocampal-cortical interactions were correlated with performance on the spatial task, the following day, suggesting a potential mechanism of impaired consolidation in AD mice. Thus, changes in hippocampal-cortical brain dynamics during sleep may underlie early memory deficits in AD.

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The Fall of Sleep K-Complex in Alzheimer Disease

Cited by 88 publications

References 66 publications

Cortical and subcortical hemodynamic changes during human sleep slow waves

Cortical and subcortical hemodynamic changes during human sleep slow waves

Sleep efficiency and neurophysiological patterns in middle‐aged men are associated with cognitive change over their adult life course

Impaired Hippocampal-cortical interactions during sleep and memory reactivation without consolidation in a mouse model of Alzheimer’s disease

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