Sleep in Alzheimer's Disease: Further Considerations on the Role of Brainstem and Forebrain Cholinergic Populations in Sleep-Wake Mechanisms

Montplaisir, Jacques; Petit, Dominique; Lorrain, Dominique; Gauthier, Serge; Nielsen, Toré

doi:10.1093/sleep/18.3.145

Cited by 139 publications

(90 citation statements)

References 20 publications

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“…Alzheimer's disease [111], sporadic Creutzfeldt-Jakob disease [112], autism and Asperger's syndrome [113,114], and affective disorders [115]. In most of these cases, spindle reduction is just one of several sleep abnormalities associated with the pathology.…”

Section: Sleep Spindles In Pathologymentioning

confidence: 99%

Manipulating sleep spindles – expanding views on sleep, memory, and disease

Astori

Wimmer²,

Lüthi³

2013

Trends in Neurosciences

127

111

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Abstract:Sleep spindles are distinctive electroencephalographic (EEG) oscillations emerging during non-rapid-eye-movement sleep (NREMS) that have been implicated in multiple brain functions, including sleep quality, sensory gating, learning and memory. Despite considerable knowledge about the mechanisms underlying these neuronal rhythms, their function remains poorly understood and current views are largely based on correlational evidence. Here, we review recent studies in humans and rodents that have begun to broaden our understanding of the role of spindles in the normal and disordered brain. We show that newly identified molecular substrates of spindle oscillations, in combination with evolving technological progress, offer novel targets and tools to selectively manipulate spindles and dissect their role in sleep-dependent processes. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationAstori et al. Highlights Newly recognized ion channel subtypes generating spindle rhythms are described. The contribution of spindles to arousal threshold and sleep quality is discussed. The proposed role of spindles in memory consolidation is examined. A function of thalamic spindles in neural development is suggested. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 4 Previous excellent reviews have thoroughly described cellular and network bases of spindle generation [3,6,7]. Here, we first review recent work on genetic models that has expanded the mechanistic understanding of this EEG rhythm through the modification of novel molecular substrates. We then discuss the current views about the functional aspects of spindles in brain physiology and pathology, as obtained from studies in naturally sleeping animals and humans. We highlight studies indicating that spindles are accessible for selective interventions, and that, with emerging technologies, will open avenues to decipher spindle function. Novel molecular aspects of spindle generationSleep spindles emerge from a limited set of cellular participants: the resonating core of these waxing-and-waning oscillations resides in the nRt-TC loop, which sustains repetitive burst discharges of its cellular components under the control of cortical inputs (Figure 1 Another important factor in the generation and maintenance of reticular intrinsic oscillations is the aforementioned SK2 or Kcnn2 channel. The vigorous Ca 2+ influx in nRt dendrites originating from Ca V 3.3 channels gates SK2 channels, thereby creating a burstafterhyperpolarization (bAHP) [12,19]. As T channels recover partially from inactivation duri...

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Section: Sleep Spindles In Pathologymentioning

confidence: 99%

Manipulating sleep spindles – expanding views on sleep, memory, and disease

Astori

Wimmer²,

Lüthi³

2013

Trends in Neurosciences

127

111

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“…Sleep disturbances that have been reported in AD patients include significant loss of SWS and REM sleep, as well as increases in the latency to the first REM sleep episode and an increase in the amount of wakefulness and EEG slowing during wake and during REM sleep (2,32,41). Such perturbations in sleep structure lead to the breakdown of sleep/wake circadian rhythms and marked attenuations in delta sleep (31,41,48,61,62).…”

Section: Discussionmentioning

confidence: 99%

Human apolipoprotein E4 targeted replacement in mice reveals increased susceptibility to sleep disruption and intermittent hypoxia

Kaushal

Ramesh

Gozal

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…However, there are AD-associated changes in sleep architecture including sleep phase delay [12] , increased nighttime motor activity [13] , decreased slow-wave sleep (SWS), decreased rapid eye movement (REM) sleep [14,15] and disrupted stage 2 (S2) sleep. S2 is poorly organized and sleep spindles, bursts of brain activity that define S2 sleep, are affected [16,17] .…”

Section: Introductionmentioning

confidence: 99%

A SPECT Study of Sleep Disturbance and Alzheimer’s Disease

Ismail

Herrmann

Francis

et al. 2009

Dement Geriatr Cogn Disord

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Background/Aims: This study aimed to investigate the possible association of regional cerebral perfusion and sleep loss in Alzheimer’s disease (AD). Methods: 55 AD patients were characterized as having (SL) or not having (NSL) nocturnal sleep loss based on standard AD scales assessing sleep over the previous 4 weeks. ^99mTc-ethylcysteinate dimer SPECT scans were performed in a relaxed, wakeful state. Whole-brain analysis using Statistical Parametrical Mapping (SPM5) was performed to compare perfusion across groups. In addition, the AD groups were compared to normal control (NC) subjects of comparable age and gender to provide a context for interpretation of findings. Results: SPM analysis showed increased perfusion in the right middle frontal gyrus (R-MFG, Brodman area 9, p = 0.016, familywise-error-corrected) in SL versus NSL patients. Comparison with NC subjects confirmed that perfusion in the R-MFG among SL patients did not exceed that found in NCs (relative rather than absolute hyperperfusion). Conclusions: In this sample of mild-to-moderate AD patients, relative hyperperfusion in the R-MFG is associated with reports of SL. This region may play a role in regulating sleep.

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Sleep in Alzheimer's Disease: Further Considerations on the Role of Brainstem and Forebrain Cholinergic Populations in Sleep-Wake Mechanisms

Cited by 139 publications

References 20 publications

Manipulating sleep spindles – expanding views on sleep, memory, and disease

Manipulating sleep spindles – expanding views on sleep, memory, and disease

Human apolipoprotein E4 targeted replacement in mice reveals increased susceptibility to sleep disruption and intermittent hypoxia

A SPECT Study of Sleep Disturbance and Alzheimer’s Disease

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