Abstract
Evidence shows that sleep dysfunction and β-amyloid (Aβ) deposition work synergistically to impair brain function in individuals with normal cognition, increasing the risk of developing dementia later in life. However, whether Aβ continues to play an integral role in sleep dysfunction after the onset of cognitive decline in individuals with dementia is unclear. To determine whether Aβ deposition in the brain is associated with subjective measures of sleep quality and cognition in elderly individuals with cognitive disorders. A nested survey study was conducted at the Cognitive Disorders and Comprehensive Alzheimer Disease Center of Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. Participants included patients aged 65 years and older with cognitive disorders verified by neuropsychological testing. Eligible participants were identified from a referral center-based sample of patients who underwent fluorine 18-labeled florbetaben positron emission tomography imaging at Thomas Jefferson University Hospital as part of the multicenter Imaging Dementia-Evidence for Amyloid Scanning study. Data collection and analysis occurred between November 2018 and March 2019. Sleep quality was measured via responses to sleep questionnaires, Aβ deposition was measured via fluorine 18-labeled florbetaben positron emission tomography, and cognition was measured via Mini-Mental State Examination (MMSE) performance. Of the 67 eligible participants, 52 (77.6%) gave informed consent to participate in the study. Of the 52 enrolled participants (mean [SD] age, 76.6 [7.4] years), 27 (51.9%) were women. Daytime sleepiness was associated with Aβ deposition in the brainstem (B = 0.0063; 95% CI, 0.001 to 0.012; P = .02), but not MMSE performance (B = -0.01; 95% CI, -0.39 to 0.37; P = .96). The number of nocturnal awakenings was associated with Aβ deposition in the precuneus (B = 0.11; 95% CI, 0.06 to 0.17; P < .001) and poor MMSE performance (B = -2.13; 95% CI, -3.13 to -1.13; P < .001). Mediation analysis demonstrated an indirect association between Aβ deposition and poor MMSE performance that relied on nocturnal awakenings as an intermediary (B = -3.99; 95% CI, -7.88 to -0.83; P = .01). Nighttime sleep disruption may mediate the association between Aβ and cognitive impairment, suggesting that there is an underlying sleep-dependent mechanism that links Aβ burden in the brain to cognitive decline. Further elucidation of this mechanism may improve understanding of disease processes associated with Aβ accumulation.
Highlights
Daytime sleepiness was associated with Aβ deposition in the brainstem (B = 0.0063; 95% CI, 0.001 to 0.012; P = .02), but not Mini-Mental State Examination (MMSE) performance (B = −0.01; 95% CI, −0.39 to 0.37; P = .96)
The number of nocturnal awakenings was associated with Aβ deposition in the precuneus (B = 0.11; 95% CI, 0.06 to 0.17; P < .001) and poor MMSE performance (B = −2.13; 95% CI, −3.13 to −1.13; P < .001)
Mediation analysis demonstrated an indirect association between Aβ deposition and poor MMSE performance that relied on nocturnal awakenings as an intermediary (B = −3.99; 95% CI, −7.88 to −0.83; P = .01)
Summary
Sleep dysfunction is associated with cognitive decline in the aging population.[1,2] Increasing evidence shows that sleep and circadian rhythm disturbances predispose the brain to accumulation of β-amyloid (Aβ),[1,3] a protein metabolite that impairs neuronal function and is linked to numerous cognitive disorders, including Alzheimer disease (AD), dementia with Lewy bodies, Parkinson disease dementia, cerebrovascular dementia, and frontotemporal dementia.[4,5] Studies[6,7,8,9,10,11,12] in humans have shown that a variety of poor sleep indicators, including prolonged sleep latency, increased sleep fragmentation, decreased total sleep time, and excessive daytime sleepiness, are associated with increased Aβ deposition in the brain. The relationship between sleep dysfunction and Aβ appears to be bidirectional because elevated levels of Aβ in the brain impair slow-wave sleep,[16] thereby exacerbating sleep problems.[17,18] The synergistic relationship between Aβ abnormalities and sleep dysfunction has been shown to interfere with memory consolidation and recall.[9,16] individuals with normal cognition experiencing poor sleep quality have increased brain Aβ burden and are at higher risk of developing dementia later in life.[8,10,19,20]
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