Sleep Fragmentation and the Risk of Incident Alzheimer's Disease and Cognitive Decline in Older Persons

Lim, Andrew; Kowgier, Matthew; Yu, Lei; Buchman, Aron S.; Bennett, David A.

doi:10.5665/sleep.2802

Cited by 565 publications

(465 citation statements)

References 32 publications

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“…Poor sleep quality is more frequent in MCI and AD patients compared to age‐matched good sleepers (Hita‐Yanez et al, 2012) and as many as 63% of patients with MCI, and 44% of patients with AD demonstrate sleep disturbance. The presence of sleep disorders increases the risk of future cognitive decline in normal older adults (Osorio et al, 2011; Lim et al, 2013) and faster cognitive deterioration in AD patients, suggesting a bidirectional relationship between sleep and AD (Miyata et al, 2013; Spira and Gottesman, 2017). Sleep disruption, especially the reduction in SWS and or increased wakefulness may suppress the function of the glymphatic system that could result in a decreased clearance of pathogenic proteins such as Aβ, which in turn may result in Aβ accumulation and the development of the symptoms of Alzheimer's disease (Musiek and Holtzman, 2016).…”

Section: Melatonin In the Treatment Of Circadian Rhythm And Sleep Dismentioning

confidence: 99%

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

Zisapel

2018

British J Pharmacology

498

310

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In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24 h light–dark cycle to invigorate and optimize the internal temporal order. The SCN‐activated, light‐inhibited production of melatonin conveys the message of darkness to the clock and induces night‐state physiological functions, for example, sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo‐controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, for example, circadian rhythm‐related sleep disorders, jet lag and shift work, insomnia in children with neurodevelopmental disorders, poor (non‐restorative) sleep quality, non‐dipping nocturnal blood pressure (nocturnal hypertension) and Alzheimer's disease (AD). The diminished production of melatonin at the very early stages of AD, the role of melatonin in the restorative value of sleep (perceived sleep quality) and its sleep‐anticipating effects resulting in attenuated activation of certain brain networks are gaining a new perspective as the role of poor sleep quality in the build‐up of β amyloid, particularly in the precuneus, is unravelled. As a result of the recently discovered relationship between circadian clock, sleep and neurodegeneration, new prospects of using melatonin for early intervention, to promote healthy physical and mental ageing, are of prime interest in view of the emerging link to the aetiology of Alzheimer's disease.Linked ArticlesThis article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

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Section: Melatonin In the Treatment Of Circadian Rhythm And Sleep Dismentioning

confidence: 99%

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

Zisapel

2018

British J Pharmacology

498

310

View full text Add to dashboard Cite

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“…[25][26][27] Briefly, k RA is the probability per 15-sec period of having an arousal, as indicated by movement (a nonzero activity count) after a sustained (≥ ~5 min) period of rest (i.e., sleep). A higher k RA indicates greater sleep fragmentation.…”

Section: Assessment Of Sleep Fragmentationmentioning

confidence: 99%

Regional neocortical gray matter structure and sleep fragmentation in older adults

et al. 2015

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“…In essence, sleep impairment may represent a risk factor for the disease. In support of this hypothesis, studies show that both self-reported sleep problems [25][26][27] and rest fragmentation at night [28] increase the risk of developing dementia, including dementia caused by AD.…”

Section: Associations Between Sleep Disruption and Admentioning

confidence: 64%

“…Hahn et al [25], for example, conducted a study with 214 Swedish participants without dementia, aged ≥75 years at baseline and showed that the ones presenting with diminished selfreported sleep depth or duration were approximately 70-100% more likely to be affected by all-cause dementia and AD, measured by clinical evaluation 9 years later [25]. Lim et al [28] showed, in a study with 737 cognitively unimpaired older adults, that significant actigraphic sleep fragmentation measured during 10 days was associated with enhanced risk of developing AD at 6-year follow-up.…”

Section: Associations Between Sleep Disruption and Admentioning

confidence: 99%

Is Sleep Disruption a Risk Factor for Alzheimer’s Disease?

Macedo

Balouch

Tabet

2017

JAD

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Sleep disturbances are routinely encountered in Alzheimer's disease (AD) and affect about 25-40% of patients in the mild-to-moderate stages of the disease. In many, sleep pathology may represent a symptom of the underlying neurodegeneration. However, a history of sleep disruption occurring years prior to onset of cognitive symptoms could represent a potential risk factor for AD. The aim of the present narrative review was to evaluate current evidence linking sleep disturbances with AD development and to understand the mechanisms that may contribute to this.Although the mechanisms by which poor sleep may contribute to AD genesis is not fully understood, emerging evidence linking disturbances in the sleep wake cycle with Aβ deposition is shedding light on the relationship between sleep pathology and the subsequent development of AD. Aβ burden appears to be enhanced by sleep-wake cycle disruptions and is suspected as being an important mechanism by which sleep disruptions contribute in AD development. Other mechanisms triggered by sleep disruption may also be involved in AD development, such as brain hypoxia, oxidative stress, circadian activity rhythms disturbances, overexpression of orexins and blood brain barrier impairment. Further understanding of the link between sleep disturbances and future development of AD is still needed before sleep disturbances are clearly marked as a preventable risk factor for AD. In these circumstances, early lifestyle interventions to help increase the quantity and quality of sleep may have a favorable outcome on decreasing the incidence of AD and this needs to be investigated further.

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Sleep Fragmentation and the Risk of Incident Alzheimer's Disease and Cognitive Decline in Older Persons

Abstract: Lim ASP; Kowgier M; Yu L; Buchman AS; Bennett DA. Sleep fragmentation and the risk of incident alzheimer's disease and cognitive decline in older persons. 2013;36(7):1027-1032.

Cited by 565 publications

References 32 publications

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

Regional neocortical gray matter structure and sleep fragmentation in older adults

Is Sleep Disruption a Risk Factor for Alzheimer’s Disease?

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