Disrupted Sleep and Alzheimer’s – Is there a Link?

by | Feb 14, 2018 | 2015, Alzheimer's Disease, Brain Health, Sleep

Written by Joyce Smith, BS. This study of 26 older adults demonstrated a significant association between beta-amyloid accumulation in the brain, a reduction in NREM slow wave activity (SWA), and an increase in memory impairment.

brain healthAlzheimer’s disease is characterized by excessive deposits of cortical beta-amyloid, subcortical tau proteins, memory loss and gradual brain cell death 1. Mounting evidence for the links between sleep, beta-amyloid, memory, and Alzheimer’s continually increases and suggests that an accumulation of beta-amyloid in the medial prefrontal cortex of the brain may contribute to a vicious cycle in which sleep is disturbed and memory impaired 2.

Mender et al 3 in a previous study, found that our powerful brain waves generated during non-rapid eye movement (NREM) sleep are necessary for the transfer of memories from our hippocampus (responsible for short-term memory storage) to the frontal cortex for longer-term memory storage. Consequently, poor quality sleep in the elderly has been linked to decreased functioning in this frontal region of the brain and consequent memory loss.

Xie et al 4 in a study of mice extolled the restorative power of sleep, claiming that when we sleep, the flow of cerebrospinal fluid in the brain increases dramatically, washing away harmful waste proteins that build up between brain cells during our waking hours. Specifically, they showed that sleep is associated with a 60% increase in the brain interstitial space, which allows for an exchange of cerebrospinal fluid with interstitial fluid and an increased rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the increased removal of potentially neurotoxic waste products that accumulate in the central nervous system during our waking hours.

Knowing that NREM slow wave activity is impaired when sleep is disrupted, researchers in this study 5 attempt to demonstrate that beta-amyloid driven pathology, by impairing NREM slow wave activity and overnight memory retention, indirectly contributes to cognitive decline in our aging population. The study involved twenty-six cognitively normal older adults (aged 65-81years) with no dementia, and no neurodegenerative sleep or psychiatric disorders. All participants had PET scans done to measure beta-amyloid levels in their brains. They took a “short-delay” recognition memory test in which they were asked to memorize 120 word pairs, after which their memory recall was tested. This was followed by eight hours of sleep, during which an electroencephalogram (EEG) measured their brain waves. The following day, a “long-delay” recognition memory test was done. During this time, Magnetic Resonance Imaging scans were done on all participants to track hippocampal activity, while they recalled portions of their previously memorized words. (Memories are temporarily stored in the hippocampus before they are moved to the prefrontal cortex) 6 . Overnight memory retention was calculated by subtracting short-delay recognition scores from long-delay recognition scores 3 using an established algorithm.

Was there an association between ß amyloid pathology and NREM Slow wave activity (SWA)? Researchers found that the deposition of prefrontal cortex beta-amyloid is associated with the generation of fewer NREM slow waves (P<0.05).

Also, did the reduction in the prefrontal cortex slow waves (that were associated with higher precortex ß-amyloid) predict impaired memory retention in healthy older adults? Researchers also found that a reduction in prefrontal cortex NREM slow wave activity predicted decreased overnight memory retention (P=0.019). (Those with the highest levels of beta-amyloid had the poorest quality of sleep and consequently, performed worst on memory recall the following morning, with some participants forgetting over 50% of the information they had memorized the previous day.)

This is the first study to show that “cortical beta-amyloid pathology is associated with impaired generation of NREM slow wave oscillations that in turn predict the failure in long-term hippocampus-dependent memory consolidation”. While this study did not prove causation, it did establish that “beta amyloid and NREM sleep physiology and hippocampus-dependent memory are significantly and directionally interrelated”.

The researchers conclude that beta-amyloid may impair hippocampus-dependent memory in older adults through its impact on NREM SWA. Furthermore, they believe that sleep is a “potentially modifiable factor”; therefore, “therapeutic sleep intervention may minimize the degree of cognitive decline associated with ß-amyloid pathology in old age”.

Source: Mander, Bryce A., Shawn M. Marks, Jacob W. Vogel, Vikram Rao, Brandon Lu, Jared M. Saletin, Sonia Ancoli-Israel, William J. Jagust, and Matthew P. Walker. “β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation.” Nature neuroscience 18, no. 7 (2015): 1051.

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Posted February 14, 2018.

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:

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  2. Westerberg CE, Mander BA, Florczak SM, et al. Concurrent impairments in sleep and memory in amnestic mild cognitive impairment. Journal of the International Neuropsychological Society. 2012;18(3):490-500.
  3. Mander BA, Rao V, Lu B, et al. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nature neuroscience. 2013;16(3):357.
  4. Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. science. 2013;342(6156):373-377.
  5. Mander BA, Marks SM, Vogel JW, et al. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nature neuroscience. 2015;18(7):1051.
  6. Kim H. Neural activity that predicts subsequent memory and forgetting: a meta-analysis of 74 fMRI studies. Neuroimage. 2011;54(3):2446-2461.