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

Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Sleep (Impact Factor: 4.59). 07/2013; 36(7):1027-1032. DOI: 10.5665/sleep.2802
Source: PubMed


Cross-sectional studies suggest that sleep fragmentation is associated with cognitive performance in older adults. We tested the hypothesis that sleep fragmentation is associated with incident Alzheimer's disease (AD) and the rate of cognitive decline in older adults.
Prospective cohort study.
737 community dwelling older adults without dementia.
Sleep fragmentation was quantified from up to 10 consecutive days of actigraphy. Subjects underwent annual evaluation for AD with 19 neuropsychological tests. Over a follow-up period of up to 6 years (mean 3.3 years), 97 individuals developed AD. In a Cox proportional hazards model controlling for age, sex, and education, a higher level of sleep fragmentation was associated with an increased risk of AD (HR = 1.22, 95%CI 1.03-1.44, P = 0.02 per 1SD increase in sleep fragmentation). An individual with high sleep fragmentation (90(th) percentile) had a 1.5-fold risk of developing AD as compared with someone with low sleep fragmentation (10(th) percentile). The association of sleep fragmentation with incident AD did not vary along demographic lines and was unchanged after controlling for potential confounders including total daily rest time, chronic medical conditions, and the use of common medications which can affect sleep. In a linear mixed effect analysis, a 0.01 unit increase in sleep fragmentation was associated with a 22% increase in the annual rate of cognitive decline relative to the average rate of decline in the cohort (Estimate = -0.016, SE = 0.007, P = 0.03).
Sleep fragmentation in older adults is associated with incident AD and the rate of cognitive decline.
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. SLEEP 2013;36(7):1027-1032.

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    • "In AD, both sleep and circadian dysfunction are commonly reported. While sleep disturbances in AD are beyond the scope of this discussion and have been reviewed elsewhere (Ju et al., 2014; Peter-Derex et al., 2014), it is important to mention that subtle sleep disturbances appear to occur early in the disease process and may predict amyloid-beta (Aβ) plaque pathology and precede subsequent development of clinical dementia (Ju et al., 2013; Lim et al., 2013a; Spira et al., 2013). Disrupted circadian rhythms in activity, physiologic parameters, and melatonin secretion have been reported in AD reported by several groups (Witting et al., 1990; Skene and Swaab, 2003; Hatfield et al., 2004; Wu et al., 2006; Hu et al., 2009; Coogan et al., 2013). "
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    ABSTRACT: Disturbance of the circadian system, manifested as disrupted daily rhythms of physiologic parameters such as sleep, activity, and hormone secretion, has long been observed as a symptom of several neurodegenerative diseases, including Alzheimer disease. Circadian abnormalities have generally been considered consequences of the neurodegeneration. Recent evidence suggests, however, that circadian disruption might actually contribute to the neurodegenerative process, and thus might be a modifiable cause of neural injury. Herein we will review the evidence implicating circadian rhythms disturbances and clock gene dysfunction in neurodegeneration, with an emphasis on future research directions and potential therapeutic implications for neurodegenerative diseases.
    Frontiers in Pharmacology 02/2015; 6:29. DOI:10.3389/fphar.2015.00029 · 3.80 Impact Factor
    • "SWS is strongly reduced in aging related disorders like mild cognitive dementia and associated with cortical thinning and prefrontal cortical atrophy (Mander et al., 2013; Sanchez–Espinosa et al., 2014). Furthermore, reduced sleep quality and sleep fragmentation in non-demented elderly participants are reliable predictors for later cognitive decline, increased amyloid beta disposition and development of Alzheimer's disease after several years (Keage et al., 2012; Lim et al., 2013; see Pace-schott and Spencer, 2014 for a review). Frequently prescribed sleep-inducing drugs typically hinder the occurrence of SWS, loose their efficacy during long-term treatment, have adverse side effects and often a high risk of addiction (Hajak and Rüther, 2006; Riemann and Perlis, 2009). "
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    ABSTRACT: Sleep quality markedly declines across the human lifespan. Particularly the amount of slow-wave sleep (SWS) decreases with age and this decrease is paralleled by a loss of cognitive functioning in the elderly. Here we show in healthy elderly females that the amount of SWS can be extended by a hypnotic suggestion “to sleep deeper” before sleep. In a placebo-controlled cross-over design, participants listened to hypnotic suggestions or a control tape before a midday nap while high density electroencephalography was recorded. After the hypnotic suggestion, we observed a 57% increase in SWS in females suggestible to hypnosis as compared to the control condition. Furthermore, left frontal slow-wave activity (SWA), characteristic for SWS, was significantly increased, followed by a significant improvement in prefrontal cognitive functioning after sleep. Our results suggest that hypnotic suggestions might be a successful alternative for widely-used sleep-enhancing medication to extend SWS and improve cognition in the elderly.
    Neuropsychologia 02/2015; DOI:10.1016/j.neuropsychologia.2015.02.001 · 3.30 Impact Factor
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    • "In addition, disrupted sleep–wake rhythms (eg, chronic shift work) can strongly increase the risk for cancer.5,6 Sleep loss and disruption can also lead to weakened immune system function,7,8 diminished memory consolidation,9 disrupted neuroendocrine function, including changes in glucose metabolism,10–12 and cognitive decline, including a diagnosis of Alzheimer’s disease.13,14 Not only does impaired sleep lead to the development of many illnesses, it is also associated with impaired healing and recovery,15–17 perhaps reflecting a further association with weakened immune system function.7,8 "
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    ABSTRACT: Maintaining a stable and adequate sleeping pattern is associated with good health and disease prevention. As a restorative process, sleep is important for supporting immune function and aiding the body in healing and recovery. Aging is associated with characteristic changes to sleep quantity and quality, which make it more difficult to adjust sleep–wake rhythms to changing environmental conditions. Sleep disturbance and abnormal sleep–wake cycles are commonly reported in seriously ill older patients in the intensive care unit (ICU). A combination of intrinsic and extrinsic factors appears to contribute to these disruptions. Little is known regarding the effect that sleep disturbance has on health status in the oldest of old (80+), a group, who with diminishing physiological reserve and increasing prevalence of frailty, is at a greater risk of adverse health outcomes, such as cognitive decline and mortality. Here we review how sleep is altered in the ICU, with particular attention to older patients, especially those aged 80 years. Further work is required to understand what impact sleep disturbance has on frailty levels and poor outcomes in older critically ill patients.
    Clinical Interventions in Aging 06/2014; 9:969. DOI:10.2147/CIA.S59927 · 2.08 Impact Factor
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