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Cited by 8Obstructive Sleep Apnea ResearchSleep and Wakefulness ResearchSleep and related disorders

Sleep spindles are reduced in children with Down syndrome and sleep-disordered breathing

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Shetty, Marisha, Davey, Margot J., Nixon, Gillian M., Walter, Lisa M., Horne, Rosemary S. C.·2024·Pediatric Research
DOI 10.1038/s41390-023-02854-1PMC PMC11343711
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Abstract

Background: Children with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB). We investigated sleep spindle activity, as a marker of sleep quality, and its relationship with daytime functioning in children with DS compared to typically developing (TD) children. Methods: Children with DS and SDB (n = 44) and TD children matched for age, sex and SDB severity underwent overnight polysomnography. Fast or Slow sleep spindles were identified manually during N2/N3 sleep. Spindle activity was characterized as spindle number, density (number of spindles/h) and intensity (density × average duration) on central (C) and frontal (F) electrodes. Parents completed the Child Behavior Check List and OSA-18 questionnaires. Results: In children with DS, spindle activity was lower compared to TD children for F Slow and F Slow&Fast spindles combined (p < 0.001 for all). Furthermore, there were no correlations between spindle activity and CBCL subscales; however, spindle activity for C Fast and C Slow&Fast was negatively correlated with OSA-18 emotional symptoms and caregiver concerns and C Fast activity was also negatively correlated with daytime function and total problems. Conclusions: Reduced spindle activity in children with DS may underpin the increased sleep disruption and negative effects of SDB on quality of life and behavior. Impact: Children with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB), which is associated with sleep disruption affecting daytime functioning. Sleep spindles are a sensitive marker of sleep quality. We identified for the first time that children with DS had reduced sleep spindle activity compared to typically developing children matched for SDB severity. The reduced spindle activity likely underpins the more disrupted sleep and may be associated with reduced daytime functioning and quality of life and may also be an early biomarker for an increased risk of developing dementia later in life in children with DS.

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  • Sleep spindles are disrupted or completely absent in individuals with DS within the first year of life.

    “Furthermore, sleep spindles, which are thought to be reflective of memory potentiation and consolidation, are disrupted or completely absent in individuals with DS within the first year of life139.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [139]

    The Results report reduced spindle activity in children with Down syndrome and no recorded spindles in two of them. But the Methods (Subjects; page unavailable) specify that participants were aged 3–19 years, so the paper does not establish that this occurs within the first year of life. The Discussion also describes a proposed role for spindles in memory consolidation. (LLM, conf=0.90)

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  1. [1]Marcus, C. L. et al. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 130, e714–e755 (2012). 22926176
  2. [2]Biggs, S. N., Nixon, G. M. & Horne, R. S. C. The conundrum of primary snoring in children: what are we missing in regards to cognitive and behavioural morbidity? Sleep. Med. Rev. 18, 463–475 (2014). 25060969
  3. [3]Beebe, D. W. & Gozal, D. Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. J. Sleep. Res. 11, 1–16 (2002). 11869421
  4. [4]Yang, J. S. C. et al. Determining sleep quality in children with sleep disordered breathing: EEG spectral analysis compared with conventional polysomnography. Sleep 33, 1165 (2010). 20857862 PMC2938856
  5. [5]Walter, L. M. et al. Age and autonomic control, but not cerebral oxygenation, are significant determinants of EEG spectral power in children. Sleep42, zsz118 (2019). 31181147
  6. [6]Silber, M. H. et al. The visual scoring of sleep in adults. J. Clin. Sleep. Med. 3, 121–131 (2007). 17557422
  7. [7]De Gennaro, L. & Ferrara, M. Sleep spindles: an overview. Sleep. Med. Rev. 7, 423–440 (2003). 14573378
  8. [8]Molle, M., Bergmann, T. O., Marshall, L. & Born, J. Fast and slow spindles during the sleep slow oscillation: disparate coalescence and engagement in memory processing. Sleep 34, 1411–1421 (2011). 21966073 PMC3174843
  9. [9]Steriade, M. Brainstem activation of thalamocortical systems. Brain Res. Bull. 50, 391–392 (1999). 10643450
  10. [10]Dang-Vu, T. T. et al. Spontaneous brain rhythms predict sleep stability in the face of noise. Curr. Biol. 20, R626–R627 (2010). 20692606
  11. [11]Dang-Vu, T. T. et al. Sleep spindles predict stress-related increases in sleep disturbances. Front. Hum. Neurosci. 9, 68 (2015). 25713529 PMC4322643
  12. [12]Fogel, S. M. & Smith, C. T. The function of the sleep spindle: a physiological index of intelligence and a mechanism for sleep-dependent memory consolidation. Neurosci. Biobehav. Rev. 35, 1154–1165 (2011). 21167865
  13. [13]Gruber, R. & Wise, M. S. Sleep spindle characteristics in children with neurodevelopmental disorders and their relation to cognition. Neural. Plast. 2016, 4724792 (2016). 27478646 PMC4958463
  14. [14]Chatburn, A. et al. Sleep spindle activity and cognitive performance in healthy children. Sleep 36, 237–243 (2013). 23372271 PMC3543056
  15. [15]Geiger, A. et al. The sleep EEG as a marker of intellectual ability in school age children. Sleep 34, 181–189 (2011). 21286251 PMC3022938
  16. [16]Hoedlmoser, K. et al. Slow sleep spindle activity, declarative memory, and general cognitive abilities in children. Sleep 37, 1501–1512 (2014). 25142558 PMC4153050
  17. [17]Tao, P. et al. Comparison of polysomnography in people with Alzheimer’s disease and insomnia versus non-demented elderly people with insomnia. Sleep. Med. 101, 515–521 (2023). 36529106
  18. [18]Horne, R. S., Wijayaratne, P., Nixon, G. M. & Walter, L. M. Sleep and sleep disordered breathing in children with Down syndrome: effects on behaviour, neurocognition and the cardiovascular system. Sleep. Med. Rev. 44, 1–11 (2018). 30576943
  19. [19]Shott, S. R. et al. Obstructive sleep apnea: should all children with Down syndrome be tested? Arch. Otolaryngol. Head. Neck Surg. 132, 432–436 (2006). 16618913
  20. [20]Subramanyam, R. et al. Upper airway morphology in Down syndrome patients under dexmedetomidine sedation. Braz. J. Anesthesiol. 66, 388 (2016). 27343789
  21. [21]Chen, C. C., Spano, G. & Edgin, J. O. The impact of sleep disruption on executive function in Down syndrome. Res. Dev. Disabil. 34, 2033–2039 (2013). 23584183
  22. [22]Churchill, S. S., Kieckhefer, G. M., Bjornson, K. F. & Herting, J. R. Relationship between sleep disturbance and functional outcomes in daily life habits of children with Down syndrome. Sleep 38, 61–71 (2015). 25325444 PMC4262957
  23. [23]Breslin, J. et al. Obstructive sleep apnea syndrome and cognition in Down syndrome. Dev. Med. Child Neurol. 56, 657–664 (2014). 24471822
  24. [24]Brooks, L. et al. Relationship between sleep, sleep apnea, and neuropsychological function in children with Down syndrome. Int. J. Sci. Pract. Sleep. Med. 19, 197–204 (2015). 24801138
  25. [25]Lee, N. C. et al. Rem sleep and sleep apnea are associated with language function in Down syndrome children: an analysis of a community sample. J. Formos. Med. Assoc. 119, 516–523 (2020). 31378642
  26. [26]Joyce, A. & Dimitriou, D. Sleep-disordered breathing and cognitive functioning in preschool children with and without Down syndrome. J. Intellect. Disabil. Res. 61, 778–791 (2017). 28612424
  27. [27]Joyce, A. et al. Obstructive sleep apnoea contributes to executive function impairment in young children with Down syndrome. Behav. Sleep. Med. 18, 611–621 (2020). 31311334
  28. [28]Sibarani, C. R. et al. Sleep-disordered breathing and sleep macro- and micro-architecture in children with Down syndrome. Pediatr. Res. 91, 1248–1256 (2022). 34230620
  29. [29]Berry, R. B. et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. Deliberations of the sleep apnea definitions task force of the American Academy of Sleep Medicine. J. Clin. Sleep. Med. 8, 597–619 (2012). 23066376 PMC3459210
  30. [30]Ogden, C. L. et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109, 45–60 (2002). 11773541
  31. [31]Shetty, M. et al. The effects of sleep disordered breathing on sleep spindle activity in children and the relationship with sleep, behavior and neurocognition. Sleep. Med. 101, 468–477 (2023). 36521367
  32. [32]Franco, R. A. Jr., Rosenfeld, R. M. & Rao, M. Quality of life for children with obstructive sleep apnea. Otolaryngol. Head. Neck Surg. 123, 9–16 (2000). 10889473
  33. [34]Oakland, T. & Harrison, P. L. Adaptive Behavior Assessment System-II (Academic Press, 2008).
  34. [35]Biggs, S. N. et al. Psychometric properties of an omnibus sleep problems questionnaire for school-aged children. Sleep. Med. 13, 390–395 (2012). 22342026
  35. [36]Janssen, K. C. et al. Validation of the Epworth Sleepiness Scale for Children and Adolescents using Rasch analysis. Sleep. Med. 33, 30–35 (2017). 28449902
  36. [39]Shibagaki, M. & Kiyono, S. Duration of spindle bursts during nocturnal sleep in mentally retarded children. Electroencephalogr. Clin. Neurophysiol. 55, 645–651 (1983). 6189694
  37. [40]Fernandez, F. & Edgin, J. O. Poor sleep as a precursor to cognitive decline in Down syndrome: a hypothesis. J. Alzheimers Dis. Parkinsonism 3, 124 (2013). 24558640 PMC3928031
  38. [41]Pulver, R. L. et al. Mapping sleep’s oscillatory events as a biomarker of Alzheimer’s disease. Preprint at bioRxiv (2023). PMC10840635 37610059
  39. [43]Levanon, A., Tarasiuk, A. & Tal, A. Sleep characteristics in children with Down syndrome. J. Pediatr. 134, 755–760 (1999). 10356146
  40. [44]O’Driscoll, D. M. et al. Cardiac and sympathetic activation are reduced in children with Down syndrome and sleep disordered breathing. Sleep 35, 1269 (2012). 22942505 PMC3413804
  41. [45]Nisbet, L. C., Phillips, N. N., Hoban, T. F. & O’Brien, L. M. Characterization of a sleep architectural phenotype in children with Down syndrome. Sleep. Breath. 19, 1065–1071 (2015). 25500979
  42. [46]Mims, M. et al. Characterization of sleep architecture in Down syndrome patients pre and post airway surgery. Cureus 9, e983 (2017). 28229031 PMC5315574
  43. [47]Ashworth, A., Hill, C. M., Karmiloff-Smith, A. & Dimitriou, D. The importance of sleep: attentional problems in school-aged children with Down syndrome and Williams syndrome. Behav. Sleep. Med. 13, 455–471 (2015). 25127421
  44. [48]Sawatari, H. et al. Characteristics of sleep-disordered breathing in children with Down syndrome – a comparison with typically developing children. Sleep. Med. X 4, 100045 (2022). 35495734 PMC9044005
  45. [49]Schabus, M. et al. Hemodynamic cerebral correlates of sleep spindles during human non-rapid eye movement sleep. Proc. Natl Acad. Sci. USA 104, 13164–13169 (2007). 17670944 PMC1941810
  46. [50]Shinomiya, S., Nagata, K., Takahashi, K. & Masumura, T. Development of sleep spindles in young children and adolescents. Clin. Electroencephalogr. 30, 39–43 (1999). 10358781
  47. [51]Ricci, A. et al. Sex and pubertal differences in the maturational trajectories of sleep spindles in the transition from childhood to adolescence: a population-based study. eNeuro8, ENEURO.0257-21.2021 (2021). PMC8281264 34168053
  48. [52]Tarokh, L., Carskadon, M. A. & Achermann, P. Trait-like characteristics of the sleep EEG across adolescent development. J. Neurosci. 31, 6371–6378 (2011). 21525277 PMC3758563
  49. [53]Piantoni, G. et al. Individual differences in white matter diffusion affect sleep oscillations. J. Neurosci. 33, 227–233 (2013). 23283336 PMC6618630
  50. [54]Gruber, R. et al. The association between sleep spindles and IQ in healthy school-age children. Int. J. Psychophysiol. 89, 229–240 (2013). 23566888
  51. [55]Marshall, L., Helgadottir, H., Molle, M. & Born, J. Boosting slow oscillations during sleep potentiates memory. Nature 444, 610–613 (2006). 17086200
  52. [57]Dworak, M. et al. Increased slow wave sleep and reduced stage 2 sleep in children depending on exercise intensity. Sleep. Med. 9, 266–272 (2008). 17644426
  53. [58]Hoedlmoser, K. et al. Instrumental conditioning of human sensorimotor rhythm (12-15 Hz) and its impact on sleep as well as declarative learning. Sleep 31, 1401–1408 (2008). 18853937 PMC2572745
  54. [59]Sterman, M. B., Howe, R. C. & Macdonald, L. R. Facilitation of spindle-burst sleep by conditioning of electroencephalographic activity while awake. Science 167, 1146–1148 (1970). 5411633
  55. [60]Mednick, S. C. et al. The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study. J. Neurosci. 33, 4494–4504 (2013). 23467365 PMC3744388
  56. [61]Poudel, G. R. et al. Functional changes during working memory in Huntington’s disease: 30-month longitudinal data from the IMAGE-HD study. Brain Struct. Funct. 220, 501–512 (2015). 24240602
  57. [62]Brockmann, P. E., Bruni, O., Kheirandish-Gozal, L. & Gozal, D. Reduced sleep spindle activity in children with primary snoring. Sleep. Med. 65, 142–146 (2020). 31869690
  58. [63]Brockmann, P. E. et al. Sleep spindle activity in children with obstructive sleep apnea as a marker of neurocognitive performance: a pilot study. Eur. J. Paediatr. Neurol. 22, 434–439 (2018). 29477593
  59. [64]Brockmann, P. E., Ferri, R. & Bruni, O. Association of sleep spindle activity and sleepiness in children with sleep-disordered breathing. J. Clin. Sleep. Med. 16, 583–589 (2020). 32022667 PMC7161436
  60. [65]DelRosso, L. M. et al. Sleep spindles in children with restless sleep disorder, restless legs syndrome and normal controls. Clin. Neurophysiol. 132, 1221–1225 (2021). 33867265

Cited by

Sorted by citations

Authors
Shetty, M., Davey, M. J., Nixon, G. M., Walter, L. M., & Horne, R. S. C.
Affiliations
  • Monash University (AU)
  • Monash Children’s Hospital (AU)
Corresponding author
Horne, Rosemary S. C.
ORCID
Venue
Pediatric Research
Publisher
Springer Science and Business Media LLC
Published
2023-10-16
Volume
96
Issue
2
Pages
457-470
ISSN
  • 0031-3998 (ISSN-L)
  • 1530-0447
DOI
10.1038/s41390-023-02854-1
PMC
PMC11343711
OpenAlex
W4387667327
Cited by
8
References
4
Citations by year
2026: 2 · 2025: 4 · 2024: 2
FWCI
1.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Pediatric Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Medical Research Council
  • National Health and Medical Research Council (1195453)
Topics
  • Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords
Down syndrome, sleep-disordered breathing, sleep spindles, slow-wave sleep, sleep quality, obstructive sleep apnea, daytime functioning, emotional symptoms, quality of life, biomarkers, dementia risk, children
MeSH terms
Sleep Quality, Child, Down Syndrome, Electroencephalography, Female, Humans, Male, Surveys and Questionnaires, Sleep, Sleep Apnea Syndromes, Case-Control Studies, Polysomnography

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