Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly

Abstract

Study Objectives: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Aβ). We thus aimed to examine relationships between concentrations of Aβ42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. Methods: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Aβ42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" Aβ42 groups to compare SWS bout length using survival analyses. Results: A significant inverse correlation was found between CSF Aβ42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Aβ42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Aβ42. Conclusions: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Aβ42, suggesting that disturbed sleep might drive an increase in soluble brain Aβ levels prior to amyloid deposition.

Amyloid Burden in Obstructive Sleep Apnea

“…In cognitively normal elderly without OSA, reduced and fragmented slow wave sleep is associated with increased CSF amyloid [26], which suggests the augmented production and clearance of amyloid. Actigraphic sleep fragmentation is related to incident AD and cognitive decline [27], and better sleep consolidation attenuates the risk of incident AD [28].…”

The Accuracy, Night-to-Night Variability, and Stability of Frontopolar Sleep Electroencephalography Biomarkers

“…2,7,8 When these patients were stratified by condition, reduced slow wave sleep was noted in those with hypertension, but not depression, sleeping aids, or obstructive sleep apnea. It is unlikely, however, that the clinical application of this sleep biomarker can be broadened when the human scoring of standard PSG is not only time consuming and expensive, but unreliable.…”

“…For example, sleep spindle characteristics during non-rapid eye movement (NREM) sleep have been associated with cognitive decline in patients with Parkinson disease, [3][4][5] and reduced slow wave sleep has been associated with increased beta amyloid (directly linked to Alzheimer disease) concentrations in the cerebrospinal fluid. 6 Because sleep spindles and slow wave sleep are believed to be associated with the metabolic clearance systems of the brain, 7 it is now argued that the routine monitoring of change in these measures are useful in evaluating the risk for, or progression of neurodegeneration. 8 …”

Sleep and mild cognitive impairment

“…A recent study by Varga, et al (Varga et al 2016) found higher levels of amyloid beta in the brain, the deposition of which remains a hallmark of Alzheimer's Disease (AD), which are associated with reduced and fragmented slow-wave sleep. Further, the daytime sleepiness and nighttime experience of parasomnias, such a rapid eye movement (REM) behavior disorder (RBD), observed in association with Lewy Body and Parkinson's related dementia, provide yet another example of disturbed sleep's connection to cognitive impairment.…”