Sleep Quality Predicts Beta-Amyloid Accumulation Across Subsequent Years

by | Feb 15, 2021 | 2020, Brain Health, Cognitive Health, Sleep

Written by Joyce Smith, BS. This study demonstrates that reduced slow-wave activity and low sleep efficiency at baseline are both associated with accelerated rate of cortical b-amyloid (Aß) plaque deposition.

Study data show that self-reported daytime sleepiness 1 and sleep apnea 2 are predictors of greater Aß plaque accumulation. In rodents, sleep restriction increases levels of Aß in brain interstitial fluids, and Aß plaques increase following chronic sleep deprivation 3. When healthy adults have insufficient non-rapid eye movement (NREM) slow-wave sleep (SWS), they have higher next day circulating levels of Aß in their cerebrospinal fluid (CSF). Higher levels of restorative SWS increase the clearance of Aß in CSF 4. Although the rate of brain Aß accumulation has been linked with declining cognitive function over time, Aß deposition can occur years in advance of cognitive impairment 5.

A 2017 study revealed that by improving sleep in a mouse model of Alzheimer’s disease (AD), in which the animals’ slow wave sleep was disrupted, the progression of AD was halted 6. Winer and colleagues 7, building on this knowledge, sought to determine whether disruptors of sleep rhythm contribute to the accumulation of brain Aß amyloid in AD or whether sleep rhythm disruptors are artifacts of disease progression.  To that end, they selected 32 cognitively healthy adults (average age 75) from the Berkeley Aging Cohort Study. All participants underwent a four-year sleep study during which researchers assessed the Aß progression using objective sleep polysomnography and longitudinal tracking of Aß accumulation with [11C]PiB positron emission tomography (PET) imaging.

Both the amount of NREM SWA below 1 Hz and the measure of sleep efficiency (shorter sleep duration and greater nighttime wakefulness) predicted the speed of subsequent Aß deposition over time, and these associations remained strong even when accounting for cofactors such as age, sex, and sleep apnea. Specifically, those with less baseline sleep efficiency (<1 Hz SWA) at baseline accumulated a significantly greater rate of cortical Aß accumulation over time compared to those with higher baseline SWA (>1 Hz SWA) (p = 0.002). No significant associations were found between other stages of sleep and the rate of Aß accumulation, lending credence to the importance of efficiency of sleep rather than to a specific sleep stage.

Baseline slow wave activity (<1 Hz SWA) was not significantly associated with change in any of the three cognitive domains of memory (p = 0.56), working memory (p 0.61), and executive function (p = 0.16). Sleep efficiency was also not significantly associated with change in memory (p = 0.24), working memory (p = 0.86), and executive function (p = 0.28).

Amyloid accumulation on PET scans increased at different rates in amyloid-negative and amyloid-positive individuals and researchers could not prove causation (whether poor sleep was responsible for   Aß accumulation); however, less sleep efficiency could be an indicator of present and future Aß levels. Because researcher failed to adjust for participants’ baseline amyloid levels, they could not determine whether some participants may have had more amyloid accumulation than others, independent of sleep.

This report supports the hypothesis that objective markers of human sleep are sensitive and can forecast the amount of cortical Aß plaque deposition over time. In combination with other markers 8,9, electroencephalogram (EEG) or wristwatch actigraphy can be used to assess the restorative benefits of NREM SWA or measure sleep efficiency, both of which are potentially non-invasive, repeatable, and safe tools for measuring the amount of pathological Aß progression before cognitive symptoms of AD manifest. Sleep, as an early AD biomarker, is unique in that it not only signals the progression of Aß accumulation but is itself a modifiable lifestyle factor.

Source: Winer, Joseph R., Bryce A. Mander, Samika Kumar, Mark Reed, Suzanne L. Baker, William J. Jagust, and Matthew P. Walker. “Sleep disturbance forecasts β-amyloid accumulation across subsequent years.” Current Biology 30, no. 21 (2020): 4291-4298

© 2020 Elsevier Inc.

Posted February 15, 2021.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Spira AP, An Y, Wu MN, et al. Excessive daytime sleepiness and napping in cognitively normal adults: associations with subsequent amyloid deposition measured by PiB PET. Sleep. 2018;41(10).
  2. Bubu OM, Pirraglia E, Andrade AG, et al. Obstructive sleep apnea and longitudinal Alzheimer’s disease biomarker changes. Sleep. 2019;42(6).
  3. Kang JE, Lim MM, Bateman RJ, et al. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science. 2009;326(5955):1005-1007.
  4. Ju YS, Ooms SJ, Sutphen C, et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain. 2017;140(8):2104-2111.
  5. Donohue MC, Sperling RA, Petersen R, Sun CK, Weiner MW, Aisen PS. Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons. Jama. 2017;317(22):2305-2316.
  6. Kastanenka KV, Hou SS, Shakerdge N, et al. Optogenetic Restoration of Disrupted Slow Oscillations Halts Amyloid Deposition and Restores Calcium Homeostasis in an Animal Model of Alzheimer’s Disease. PLoS One. 2017;12(1):e0170275.
  7. Winer JR, Mander BA, Kumar S, et al. Sleep Disturbance Forecasts β-Amyloid Accumulation across Subsequent Years. Current biology : CB. 2020.
  8. Hadoux X, Hui F, Lim JKH, et al. Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer’s disease. Nat Commun. 2019;10(1):4227.
  9. Thijssen EH, La Joie R, Wolf A, et al. Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Nat Med. 2020;26(3):387-397.