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Cited by 111Sleep and Wakefulness ResearchDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

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The Fall of Sleep K-Complex in Alzheimer Disease

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De Gennaro, Luigi, Gorgoni, Maurizio, Reda, Flaminia, Lauri, Giulia, Truglia, Ilaria, Cordone, Susanna, Scarpelli, Serena, Mangiaruga, Anastasia, D’atri, Aurora, Lacidogna, Giordano, Ferrara, Michele, Marra, Camillo, Rossini, Paolo Maria·2017·Scientific Reports
DOI 10.1038/srep39688PMC PMC5206737
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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.

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  • These graphoelements have been addressed as markers for early cognitive deterioration conditions, such as Alzheimer's disease, where memory deterioration is one of the main complaints.

    “These graphoelements have been addressed as markers for early cognitive deterioration conditions, such as Alzheimer’s disease,127–129 where memory deterioration is one of the main complaints.”

    From Spotlight on dream recall: the ages of dreams (2018) · cites this paper as [127]

    The Results section, ‘The relation between KCs and cognitive impairment’ (page unavailable), reports that K-complex density predicted cognitive-impairment scores, and the Conclusions report fewer frontal K-complexes in patients with Alzheimer’s disease. The paper does not establish K-complexes as markers of early deterioration; its Conclusions call for prospective studies of their association with cognitive decline. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Age-related microstructural changes of sleep have been linked to cognitive deterioration.

    “age-related microstructural changes of sleep have been linked to cognitive deterioration.123,127–129”

    From Spotlight on dream recall: the ages of dreams (2018) · cites this paper as [127]

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Research works printed but not linked: 57

  1. Peter-Derex, L., Yammine, P., Bastuji, H. & Croisile, B. Sleep and Alzheimer’s disease. Sleep. Med. Rev. 19, 29–38 (2015). · DOI
  2. Bliwise, D. L. Sleep disorders in Alzheimer’s disease and other dementias. Neurodegener. Dis. 6, S16–S28 (2004).
  3. Dauwels, J., Vialatte, F. & Cichocki, A. Diagnosis of Alzheimer’s disease from EEG signals: where are we standing? Curr. Alzheimer Res. 7, 487–505 (2010). · DOI
  4. Bonanni, L. et al. EEG comparisons in early Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease with dementia patients with a 2-year follow-up. Brain 131, 690–705 (2008). · DOI
  5. Petit, D., Gagnon, J. F., Fantini, M. L., Ferini-Strambi, L. & Montplaisir, J. Sleep and quantitative EEG in neurodegenerative disorders. J. Psychosom. Res. 56(5), 487–496 (2004). · DOI
  6. Gorgoni, M. et al. Parietal fast sleep spindle density decrease in Alzheimer’s disease and amnesic Mild Cognitive Impairment. Neural Plast. 10.1155/2016/8376108 (2016). · DOI · Paper page
  7. Bonanni, E. et al. Differences in EEG delta frequency characteristics and patterns in slow-wave-sleep between dementia patients and controls: a pilot study. J. Clin. Neurophysiol. 29, 50–54 (2012). · DOI
  8. Mander, B. A. et al. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat. Neurosci. 18, 1051–1057 (2015). · DOI · Paper page
  9. Mander, B. A. et al. Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging. Nat. Neurosci. 16, 357–364 (2013). · DOI · Paper page
  10. Cash, S. S. et al. The human K-complex represents an isolated cortical down-state. Science 324, 1084–1087 (2009). · DOI · Paper page
  11. Colrain, I. M. The K-complex: a 7-decade history. Sleep 28, 255–273 (2005). · DOI
  12. Contreras, D. & Steriade, M. Cellular basis of EEG slow rhythms: a study of dynamic corticothalamic relationships. J. Neurosci. 15(1Pt 2), 604–622 (1995). · DOI
  13. Amzica, F. & Steriade, M. The K-complex: its slow (<1-Hz) rhythmicity and relation to delta waves. Neurology. 49(4), 952–959 (1997). · DOI
  14. Amzica, F. & Steriade, M. The functional significance of K-complexes. Sleep Med. Rev. 6, 139–149 (2002). · DOI
  15. De Gennaro, L., Ferrara, M. & Bertini, M. The spontaneous K-complex during stage 2 sleep: is the ‘forerunner’ of delta waves? Neurosci. Lett. 291, 41–43 (2000). · DOI
  16. Curcio, G., Ferrara, M., Pellicciari, M. C., Cristiani, R. & De Gennaro, L. Effect of total sleep deprivation on the landmarks of stage 2 sleep. Clin. Neurophysiol. 114, 2279–2285 (2003). · DOI
  17. Amzica, F. & Steriade, M. Electrophysiological correlates of sleep delta waves. Electroencephalogr. Clin. Neurophysiol. 107, 69–83 (1998). · DOI · Paper page
  18. Wennberg, R. Intracranial cortical localization of the human K-complex. Clin. Neurophysiol. 121, 1176–1186 (2010). · DOI
  19. Jahnke, K. et al. To wake or not to wake? The two-sided nature of the human K-complex. Neuroimage 59, 1631–1638 (2011). · DOI
  20. Davis, H., Davis, P. A., Loomis, A. L., Harvey, E. N. & Hobart, G. Electrical reactions of the human brain to auditory stimulation during sleep. J. Neurophysiol. 2, 500–514 (1939). · DOI
  21. Cote, K. A., de Lugt, D. R., Langley, S. D. & Campbell, K. B. Scalp topography of the auditory evoked K-complex in stage 2 and slow wave sleep. J. Sleep Res. 8, 263–272 (1999). · DOI
  22. Colrain, I. M. et al. Independent contributions of cortical gray matter, aging sex and alcoholism to K-complex amplitude evoked during sleep. Sleep 34, 787–795 (2011). · DOI
  23. Crowley, K., Trinder, J., Kim, Y., Carrington, M. & Colrain, I. M. The effects of normal aging on sleep spindle and K-complex production. Clin. Neurophysiol. 113, 1615–1622 (2002). · DOI · Paper page
  24. Kubicki, S., Scheuler, W., Jobert, M. & Pastelak-Price, C. The effect of age on sleep spindle and K complex density. EEG EMG Z Elektroenzephalogr. Elektromyogr. Verwandte. Geb. 20, 59–63 (1989).
  25. Colrain, I. M. et al. Sleep evoked delta frequency responses show a linear decline in amplitude across the adult lifespan. Neurobiol. Aging 31, 874–883 (2010). · DOI
  26. Crowley, K., Trinder, J. & Colrain, I. M. An examination of evoked K-complex amplitude and frequency of occurrence in the elderly. J. Sleep Res. 11, 129–140 (2002). · DOI
  27. Crowley, K., Trinder, J. & Colrain, I. M. Evoked K-complex generation: the impact of sleep spindles and age. Clin. Neurophysiol. 115, 471–476 (2004). · DOI
  28. Prinz, P. N. et al. Changes in the sleep and waking EEGs of nondemented and demented elderly subjects. J. Am. Geriatr. Soc. 30, 86–93 (1982). · DOI
  29. Reynolds, C. F. et al. EEG sleep in elderly depressed, demented, and healthy subjects. Biol. Psychiatry 20, 431–442 (1985). · DOI
  30. Montplaisir, J., Petit, D., Lorrain, D., Gauthier, S. & Nielsen, T. Sleep in Alzheimer’s disease: further considerations on the role of brainstem and forebrain cholinergic populations in sleep-wake mechanisms. Sleep 18, 145–148 (1995). · DOI
  31. Nicholas, C. L., Trinder, J., Crowley, K. E. & Colrain, I. M. The impact of slow wave sleep proximity on evoked K-complex generation. Neurosci. Lett. 404, 127–131 (2006). · DOI
  32. Amzica, F. & Massimini, M. Glial and neuronal interactions during slow wave and paroxysmal activities in the neocortex. Cereb. Cortex 12, 1101–1113 (2002). · DOI
  33. Crowley, K., Sullivan, E. V., Adalsteinsson, E., Pfefferbaum, A. & Colrain, I. A. Differentiating pathologic delta from healthy physiologic delta in patients with Alzheimer disease. Sleep 28, 865–870 (2005). · DOI
  34. Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T. & DeLong, M. R. Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann. Neurol. 10, 122–126 (1981). · DOI · Paper page
  35. Arendt, T., Bigl, V., Tennstedt, A. & Arendt, A. Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer’s disease. Neuroscience 14, 1–14 (1985). · DOI
  36. Colrain, I. M. & Crowley, K. E. Evoked potentials during non-REM sleep: utility and functional significance In Clinical Neurophysiology of Sleep Disorders, Vol. 6 (ed. Guilleminault, C. ), 125–135 (Elsevier, 2005).
  37. Tononi, G. & Cirelli, C. Sleep function and synaptic homeostasis. Sleep Med. Rev. 10, 49–62 (2006). · DOI · Paper page
  38. Westerberg, C. E. et al. Memory improvement via low-frequency stimulation during sleep in older adults. Neurobiol. Aging 36, 2577–2586 (2015). · DOI
  39. Massimini, M. et al. Triggering sleep slow waves by transcranial magnetic stimulation. Proc. Natl. Acad. Sci. USA 104, 8496–8501 (2007). · DOI · Paper page
  40. Ngo, H. V., Martinetz, T., Born, J. & Mölle, M. Auditory closed-loop stimulation of the sleep slow oscillation enhances memory. Neuron 78, 545–553 (2013). · DOI · Paper page
  41. Ngo, H. V. et al. Driving sleep slow oscillations by auditory closed-loop stimulation-a self-limiting process. J. Neurosci. 35, 6630–6638 (2015). · DOI
  42. Cox, R., Korjoukov, I., de Boer, M. & Talamini, L. M. Sound asleep: processing and retention of slow oscillation phase-targeted stimuli. PLoS ONE 9, e101567 (2014). · DOI
  43. Santostasi, G. et al. Phase locked loop for precisely timed acoustic stimulation during sleep. J. Neurosci. Methods 259, 101–114 (2015). · DOI
  44. Simor, P. et al. Lateralized rhythmic acoustic stimulation during NREM sleep. J. Sleep Res. 25(Suppl. 1), 104 (2016). · DOI
  45. Parrino, L., Ferri, R., Bruni, O. & Terzano, M. G. Cyclic alternating pattern (CAP): the marker of sleep instability. Sleep Med. Rev. 16(1), 27–45 (2012). · DOI
  46. Maestri, M. et al. NREM sleep transient events in fronto-temporal dementia: beyond sleep stage architecture. Arch. Ital. Biol. 153(2–3), 214–224 (2015).
  47. Folstein, M. F., Folstein, S. E. & McHugh, P. R. “Mini Mental State”: a practical method for grading the cognitive state of patients for clinician. J. Psychiatr. Res. 12, 189–198 (1975). · DOI · Paper page
  48. Spielberger, C. D. State-Trait Anxiety Inventory: Bibliography 2nd ed. (Consulting Psychologists Press, 1989).
  49. Hamilton, M. Development of a rating scale for primary depressive illness. Br. J. Soc. Clin. Psychol. 6, 278–296 (1967). · DOI
  50. Carlesimo, G. A., Caltagirone, C. & Gainotti, G. The Group for the Standardization of the Mental Deterioration Battery. The Mental Deterioration Battery: Normative data, diagnostic reliability and qualitative analyses of cognitive impairment. Eur. Neurol. 36, 378–384 (1996). · DOI
  51. Chandler, M. J. et al. Three-word recall in normal aging. J. Clin. Exp. Neuropsychol. 26, 1128–1133 (2004). · DOI
  52. Babiloni, C. et al. Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during rey auditory verbal learning test. Hum. Brain Mapp. 30, 2077–2089 (2009). · DOI
  53. Lawton, M. P. & Brodie, E. M. Assessment of older people: Self maintaining and instrumental activity of daily living. Gerontologist 9, 179–186 (1969). · DOI · Paper page
  54. McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 263–269 (2011). · DOI · Paper page
  55. Curcio, G. et al. Validity of the Italian Version of the Pittsburgh Sleep Quality Index (PSQI). Neurol. Sci. 34, 511–519 (2013). · DOI
  56. Vignatelli, L. et al. Italian version of the Epworth sleepiness scale external validity. Neurol. Sci. 23, 295–300 (2003). · DOI
  57. Bastien, C. H. et al. Spontaneous K-complexes in chronic psychophysiological insomnia. J. Psychosom. Res. 67, 117–125 (2009). · DOI

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Metadata

Authors
De Gennaro, L., Gorgoni, M., Reda, F., Lauri, G., Truglia, I., Cordone, S., Scarpelli, S., Mangiaruga, A., D’atri, A., Lacidogna, G., Ferrara, M., Marra, C., & Rossini, P. M.
Affiliations
  • Sapienza University of Rome (IT)
  • Università Cattolica del Sacro Cuore (IT)
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-01-03
Volume
7
Issue
1
Pages
39688-39688
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep39688
PMC
PMC5206737
OpenAlex
W2566067878
Cited by
111
References
5
Citations by year
2026: 7 · 2025: 11 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 21 · 2020: 16 · 2019: 12 · 2018: 7 · 2017: 7
FWCI
6.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
  • Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion, cc-by-nc-nd)
  • PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
Funders
Sapienza Università di Roma
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, K-complexes, slow-wave activity, NREM sleep, sleep EEG, frontal EEG, cognitive decline, amyloid-beta, stage 2 sleep
MeSH terms
Aged, Alzheimer Disease, Female, Frontal Lobe, Humans, Male, Sleep Stages, Brain Waves

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