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: 5.06). 07/2013; 36(7):1027-1032. DOI: 10.5665/sleep.2802
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The relationship between recent episodes of poor sleep and cognitive testing performance in healthy cognitively intact older adults is not well understood. In this exploratory study we examined the impact of recent sleep disturbance, sleep duration, and sleep variability on cognitive performance in 63 cognitively intact older adults using a novel unobtrusive in-home sensor-based sleep assessment methodology. Specifically, we examined the impact of sleep the night prior, the week prior, and the month prior to a neuropsychological evaluation on cognitive performance. Results showed that mildly disturbed sleep the week prior and month prior to cognitive testing was associated with reduced working memory on cognitive evaluation. One night of mild sleep disturbance was not associated with decreased cognitive performance the next day. Sleep duration was unrelated to cognition. In-home, unobtrusive, sensor monitoring technologies provide a novel method for objective, long-term, and continuous assessment of sleep behavior and other everyday activities that might contribute to decreased or variable cognitive performance in healthy older adults.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Disturbances in the sleep-wake cycle and circadian rhythms are common symptoms of Alzheimer Disease (AD), and they have generally been considered as late consequences of the neurodegenerative processes. Recent evidence demonstrates that sleep-wake and circadian disruption often occur early in the course of the disease and may even precede the development of cognitive symptoms. Furthermore, the sleep-wake cycle appears to regulate levels of the pathogenic amyloid-beta peptide in the brain, and manipulating sleep can influence AD-related pathology in mouse models via multiple mechanisms. Finally, the circadian clock system, which controls the sleep-wake cycle and other diurnal oscillations in mice and humans, may also have a role in the neurodegenerative process. In this review, we examine the current literature related to the mechanisms by which sleep and circadian rhythms might impact AD pathogenesis, and we discuss potential therapeutic strategies targeting these systems for the prevention of AD.
    Experimental and Molecular Medicine 03/2015; 47(3):e148. DOI:10.1038/emm.2014.121 · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    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