Reduced Non-Rapid Eye Movement Sleep is Associated with Early Alzheimer’s Disease

Written by Joyce Smith, BS.  Slow wave activity (SWA) during non-rapid eye movement (NREM) sleep decreases with disease progression in patients with Alzheimer’s disease. 

The early stages of Alzheimer’s disease (AD) pathogenesis are characterized by an aggregation of amyloid-ß (Aß) into oligomers and fibrils that are present in the brain in early AD and can occur 15 – 20 years before the onset of cognitive decline ¹. By the time clinical symptoms of AD appear, Aß accumulation has almost peaked and tau pathology is usually evident in the neocortex of the brain ². Aß decreases in the cerebral spinal fluid (CSF) as brain amyloid increases ³. Interestingly, the dual effect of tau/amyloid pathology as measured by the CSF tau/ Aß42 ratio is a prediction of early symptomatic AD ⁴  and the period in which AD pathology accumulates before the manifestation of cognitive symptoms is known as “preclinical” AD ⁵.

A bi-directional relationship between sleep and AD exists. Poor sleep quality, short sleep duration, and increased napping have all been associated with increased risk of cognitive decline and increased Aß deposition ⁶. Aß concentrations in CSF fluctuate with sleep-wake activity and represent an Aβ cycling pattern that has been replicated in multiple studies in both mice and humans ⁷. A recent human study demonstrated that slow wave sleep disruption ⁸ and sleep deprivation ⁹ will increase overnight CSF concentrations of Aβ by 10–30%, most likely due to an increased production and release of Aß.

The objective of this on-going longitudinal observational study ¹⁰ was to assess a potential association between sleep parameters and biomarkers of Alzheimer’s disease. Holtzman and colleagues observed the sleep-wake activity of 119 participants for six consecutive nights. All were over 60 years of age, clinically assessed for dementia, and sleep monitored in three ways: sleep logs, an electroencephalogram (EEG) (a device that measures electrical activity in the brain) worn on the forehead,  and a sleep actigraph (a device that measures sleep/awake activity) worn on the  wrist. In addition, every participant was given a home sleep test that assessed for sleep apnea and restless legs. Thirty-eight participants underwent tau brain imaging using positron emission tomography (Pet) imaging with both amyloid and tau tracers while forty-five others had a lumbar puncture to measure the amount of Aß42, total tau, and p-tau 181 in their cerebral spinal fluid (SPF). Unpaired two-tailed t-test was used to determine the differences between the groups that were amyloid negative or positive and tau negative or positive.

Analysis revealed that NREM SWA decreased with increased evidence of Aß deposition and tau accumulation. Participants with the highest level of AD pathology (particularly tau) had the lowest level of NREM SWA sleep, yet they had the greatest amount of total sleep time and also napped more, suggesting that their quality of sleep was poor. This inverse association with increased AD pathology, particularly tau, and decreased NREM SWA sleep was most prevalent at the lowest frequencies of NREM SWA sleep. Given that most study participants were cognitively normal, changes in NREM SWA at the lower frequencies, especially at the lowest 1-2 Hz frequencies, might be an effective barometer for detecting tau pathology and cognitive impairment before or at the earliest stages of symptomatic AD.

Source:  Lucey, Brendan P., Austin McCullough, Eric C. Landsness, Cristina D. Toedebusch, Jennifer S. McLeland, Aiad M. Zaza, Anne M. Fagan et al. “Reduced non–rapid eye movement sleep is associated with tau pathology in early Alzheimer’s disease.” Science translational medicine 11, no. 474 (2019): eaau6550.   

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.  

Posted February 25, 2020.

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.

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