Sleep Disturbance: An Early Sign of Alzheimer’s Disease

  • Chao HeEmail author
  • Zhian HuEmail author
  • Chenggang JiangEmail author

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with cognitive impairment in older adults. The accumulation of insoluble forms of amyloid-β (Aβ) in plaques in extracellular spaces and the aggregation of hyperphosphorylated microtubule-associated protein tau in neurofibrillary tangles in neurons are considered to be central pathological features of AD [1, 2]. Before the cognitive symptoms and pathological signs are present, preclinical synaptic and neuronal injury begins to occur, and this continues for 10–20 years. Currently, one focus of AD research is to discern the preclinical stage of AD, when Aβ deposition has begun to occur but before clear cognitive impairment, as well as to develop therapeutic interventions at this stage to prevent AD progression [3].

Sleep disturbance is recognized as a common and often highly disruptive behavioral symptom associated with AD. It has been reported that Aβ deposition pathology itself can alter sleep architecture [


  1. 1.
    Gao Y, Liu Q, Xu L, Zheng N, He X, Xu F. Imaging and spectral characteristics of amyloid plaque autofluorescence in brain slices from the APP/PS1 mouse model of Alzheimer’s disease. Neurosci Bull 2019, 35: 1126–1137.CrossRefGoogle Scholar
  2. 2.
    Wei YP, Ye JW, Wang X, Zhu LP, Hu QH, Wang Q, et al. Tau-induced Ca(2+)/calmodulin-dependent protein kinase-IV activation aggravates nuclear Tau hyperphosphorylation. Neurosci Bull 2018, 34: 261–269.CrossRefGoogle Scholar
  3. 3.
    Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, 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 2011, 7: 280–292.CrossRefGoogle Scholar
  4. 4.
    Roh JH, Huang Y, Bero AW, Kasten T, Stewart FR, Bateman RJ, et al. Disruption of the sleep-wake cycle and diurnal fluctuation of beta-amyloid in mice with Alzheimer’s disease pathology. Sci Transl Med 2012, 4: 150ra122.CrossRefGoogle Scholar
  5. 5.
    Holth JK, Fritschi SK, Wang C, Pedersen NP, Cirrito JR, Mahan TE, et al. The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science 2019, 363: 880–884.CrossRefGoogle Scholar
  6. 6.
    Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science 2013, 342: 373–377.CrossRefGoogle Scholar
  7. 7.
    Zhang F, Zhong R, Li S, Fu Z, Wang R, Wang T, et al. Alteration in sleep architecture and electroencephalogram as an early sign of Alzheimer’s disease preceding the disease pathology and cognitive decline. Alzheimers Dement 2019, 15: 590–597.CrossRefGoogle Scholar
  8. 8.
    Jyoti A, Plano A, Riedel G, Platt B. EEG, activity, and sleep architecture in a transgenic AbetaPPswe/PSEN1A246E Alzheimer’s disease mouse. J Alzheimers Dis 2010, 22: 873–887.CrossRefGoogle Scholar
  9. 9.
    Schneider F, Baldauf K, Wetzel W, Reymann KG. Behavioral and EEG changes in male 5xFAD mice. Physiol Behav 2014, 135: 25–33.CrossRefGoogle Scholar
  10. 10.
    Brayet P, Petit D, Frauscher B, Gagnon JF, Gosselin N, Gagnon K, et al. Quantitative EEG of rapid-eye-movement sleep: a marker of amnestic mild cognitive impairment. Clin EEG Neurosci 2016, 47: 134–141.CrossRefGoogle Scholar
  11. 11.
    Hot P, Rauchs G, Bertran F, Denise P, Desgranges B, Clochon P, et al. Changes in sleep theta rhythm are related to episodic memory impairment in early Alzheimer’s disease. Biol Psychol 2011, 87: 334–339.CrossRefGoogle Scholar
  12. 12.
    Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM, Bilgel M, et al. Self-reported sleep and beta-amyloid deposition in community-dwelling older adults. JAMA Neurol 2013, 70: 1537–1543.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Vitiello MV, Prinz PN, Williams DE, Frommlet MS, Ries RK. Sleep disturbances in patients with mild-stage Alzheimer’s disease. J Gerontol 1990, 45: M131–138.CrossRefGoogle Scholar
  14. 14.
    Zhang Z, Zhong P, Hu F, Barger Z, Ren Y, Ding X, et al. An excitatory circuit in the perioculomotor midbrain for non-REM sleep control. Cell 2019, 177: 1293–1307.Google Scholar
  15. 15.
    Ren S, Wang Y, Yue F, Cheng X, Dang R, Qiao Q, et al. The paraventricular thalamus is a critical thalamic area for wakefulness. Science 2018, 362: 429–434.CrossRefGoogle Scholar
  16. 16.
    Goedert M. Neurodegeneration. Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Abeta, tau, and alpha-synuclein. Science 2015, 349: 1255555.CrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  1. 1.Department of Physiology, Institute of Brain and IntelligenceThird Military Medical UniversityChongqingChina
  2. 2.Department of Medical PsychologyChongqing Health Center for Women and ChildrenChongqingChina
  3. 3.Department of Sleep and PsychologyDaping Hospital, Third Military Medical UniversityChongqingChina

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