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Sleep and Alzheimer disease pathology—a bidirectional relationship

Nature Reviews Neurology volume 10, pages 115–119 (2014)Cite this article

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Abstract

Factors other than age and genetics may increase the risk of developing Alzheimer disease (AD). Accumulation of the amyloid-β (Aβ) peptide in the brain seems to initiate a cascade of key events in the pathogenesis of AD. Moreover, evidence is emerging that the sleep–wake cycle directly influences levels of Aβ in the brain. In experimental models, sleep deprivation increases the concentration of soluble Aβ and results in chronic accumulation of Aβ, whereas sleep extension has the opposite effect. Furthermore, once Aβ accumulates, increased wakefulness and altered sleep patterns develop. Individuals with early Aβ deposition who still have normal cognitive function report sleep abnormalities, as do individuals with very mild dementia due to AD. Thus, sleep and neurodegenerative disease may influence each other in many ways that have important implications for the diagnosis and treatment of AD.

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Figure 1: The bidirectional relationship between sleep and AD.

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References

  1. Moran, M. et al. Sleep disturbance in mild to moderate Alzheimer's disease. Sleep Med. 6, 347–352 (2005).

    Article  Google Scholar 

  2. Ancoli-Israel, S. et al. Variations in circadian rhythms of activity, sleep, and light exposure related to dementia in nursing-home patients. Sleep 20, 18–23 (1997).

    Article  CAS  Google Scholar 

  3. Swaab, D. F., Fliers, E. & Partiman, T. S. The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res. 342, 37–44 (1985).

    Article  CAS  Google Scholar 

  4. Schneider, J. A., Arvanitakis, Z., Leurgans, S. E. & Bennett, D. A. The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann. Neurol. 66, 200–208 (2009).

    Article  Google Scholar 

  5. Petersen, R. C. Mild cognitive impairment as a diagnostic entity. J. Intern. Med. 256, 183–194 (2004).

    Article  CAS  Google Scholar 

  6. Westerberg, C. E. et al. Concurrent impairments in sleep and memory in amnestic mild cognitive impairment. J. Int. Neuropsychol. Soc. 18, 490–500 (2012).

    Article  Google Scholar 

  7. Sperling, R. A. et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging–Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 7, 280–292 (2011).

    Article  Google Scholar 

  8. Ju, Y. S. et al. Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 70, 587–593 (2013).

    Article  Google Scholar 

  9. Roh, J. H. et al. Disruption of the sleep-wake cycle and diurnal fluctuation of β-amyloid in mice with Alzheimer's disease pathology. Sci. Transl. Med. 4, 150ra122 (2012).

    Article  Google Scholar 

  10. Duncan, M. J. et al. Effects of aging and genotype on circadian rhythms, sleep, and clock gene expression in APPxPS1 knock-in mice, a model for Alzheimer's disease. Exp. Neurol. 236, 249–258 (2012).

    Article  CAS  Google Scholar 

  11. Platt, B. et al. Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1. PLoS ONE 6, e27068 (2011).

    Article  CAS  Google Scholar 

  12. Tworoger, S. S., Lee, S., Schernhammer, E. S. & Grodstein, F. The association of self-reported sleep duration, difficulty sleeping, and snoring with cognitive function in older women. Alzheimer Dis. Assoc. Disord. 20, 41–48 (2006).

    Article  Google Scholar 

  13. Faubel, R. et al. Usual sleep duration and cognitive function in older adults in Spain. J. Sleep Res. 18, 427–435 (2009).

    Article  Google Scholar 

  14. Blackwell, T. et al. Association of sleep characteristics and cognition in older community-dwelling men: the MrOS sleep study. Sleep 34, 1347–1356 (2011).

    Article  Google Scholar 

  15. Potvin, O. et al. Sleep quality and 1-year incident cognitive impairment in community-dwelling older adults. Sleep 35, 491–499 (2012).

    Article  Google Scholar 

  16. Lim, A. S. et al. Sleep fragmentation and the risk of incident Alzheimer's disease and cognitive decline in older persons. Sleep 36, 1027–1032 (2013).

    Article  Google Scholar 

  17. Yaffe, K. et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA 306, 613–619 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kang, J.-E. et al. Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science 326, 1005–1007 (2009).

    Article  CAS  Google Scholar 

  19. Huang, Y. et al. Effects of age and amyloid deposition on Aβ dynamics in the human central nervous system. Arch. Neurol. 69, 51–58 (2012).

    Article  Google Scholar 

  20. Maquet, P. et al. Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and 18F2-fluoro-2-deoxy-D-glucose method. Brain Res. 513, 136–143 (1990).

    Article  CAS  Google Scholar 

  21. Dang-Vu, T. T. et al. Functional neuroimaging insights into the physiology of human sleep. Sleep 33, 1589–1603 (2010).

    Article  Google Scholar 

  22. Nir, Y. et al. Regional slow waves and spindles in human sleep. Neuron 70, 153–169 (2011).

    Article  CAS  Google Scholar 

  23. Cirrito, J. R. et al. Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron 48, 913–922 (2005).

    Article  CAS  Google Scholar 

  24. Bero, A. W. et al. Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat. Neurosci. 14, 750–756 (2011).

    Article  CAS  Google Scholar 

  25. Huitrón-Reséndiz, S. et al. Age-independent and age-related deficits in visuospatial learning, sleep–wake states, thermoregulation and motor activity in PDAPP mice. Brain Res. 22, 126–137 (2002).

    Article  Google Scholar 

  26. Jagust, W. J. & Mormino, E. C. Lifespan brain activity, β-amyloid, and Alzheimer's disease. Trends Cogn. Sci. 15, 520–526 (2011).

    Article  Google Scholar 

  27. Horovitz, S. G. et al. Decoupling of the brain's default mode network during deep sleep. Proc. Natl Acad. Sci. USA 106, 11376–11381 (2009).

    Article  CAS  Google Scholar 

  28. Sämann, P. G. et al. Development of the brain's default mode network from wakefulness to slow wave sleep. Cereb. Cortex 21, 2082–2093 (2011).

    Article  Google Scholar 

  29. Mandrekar-Colucci, S., Karlo, J. C. & Landreth, G. E. Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease. J. Neurosci. 32, 10117–10128 (2012).

    Article  CAS  Google Scholar 

  30. Fagan, A. M. et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Aβ42 in humans. Ann. Neurol. 59, 512–519 (2006).

    Article  CAS  Google Scholar 

  31. Farajnia, S. et al. Evidence for neuronal desynchrony in the aged suprachiasmatic nucleus clock. J. Neurosci. 32, 5891–5899 (2012).

    Article  CAS  Google Scholar 

  32. Hastings, M. H. & Goedert, M. Circadian clocks and neurodegenerative diseases: time to aggregate? Curr. Opin. Neurobiol. 23, 880–887 (2013).

    Article  CAS  Google Scholar 

  33. Durmer, J. S. & Dinges, D. F. Neurocognitive consequences of sleep deprivation. Semin. Neurol. 25, 117–129 (2005).

    Article  Google Scholar 

  34. Lim, A. S. P. et al. Increased fragmentation of rest-activity patterns is associated with a characteristic pattern of cognitive impairment in older individuals. Sleep 35, 633–640B (2012).

    Article  Google Scholar 

  35. Vahtera, J. et al. Effect of retirement on sleep disturbances: the GAZEL prospective cohort study. Sleep 32, 1459–1466 (2009).

    Article  Google Scholar 

  36. Luik, A. I. et al. Stability and fragmentation of the activity rhythm across the sleep-wake cycle: the importance of age, lifestyle, and mental health. Chronobiol. Int. http://dx.doi.org/10.3109/07420528.2013.813528.

  37. Alzheimer's Association. Changing the trajectory of Alzheimer's disease: a national imperative. www.alz.org[online], (2010).

  38. Cardinali, D. P. et al. Therapeutic application of melatonin in mild cognitive impairment. Am. J. Neurodegener. Dis. 1, 280–291 (2012).

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors' work is supported by NIH grant P01NS074969 and the Ellison Medical Foundation Senior Scholar Award (both to D. M. Holtzman). The research described in this article was made possible by a grant to Y. S. Ju from the National Center for Research Resources (UL1 RR024992), which is a component of the NIH, and the NIH Roadmap for Medical Research.

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Authors and Affiliations

  1. Department of Neurology, Washington University School of Medicine, Washington University, 660 South Euclid Avenue, Box 8111, St Louis, 63110, MO, USA

    Yo-El S. Ju, Brendan P. Lucey & David M. Holtzman

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All authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

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Correspondence to David M. Holtzman.

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Competing interests

D. M. Holtzman is a co-founder and member of the scientific advisory board of C2N Diagnostics. He also acts as a consultant for Genentech and AstraZeneca, and his laboratory receives research grants from AstraZeneca and Eli Lilly. These interests are not related to the topic of this article. The other authors declare no competing interests.

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Ju, YE., Lucey, B. & Holtzman, D. Sleep and Alzheimer disease pathology—a bidirectional relationship. Nat Rev Neurol 10, 115–119 (2014). https://doi.org/10.1038/nrneurol.2013.269

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