Sleep Quality as a Biomarker and Predictor of Alzheimer’s Disease

Written by Joyce Smith, BS. Reduced slow-wave activity and low sleep efficiency at baseline were both associated with an accelerated rate of cortical beta-amyloid plaque deposition in healthy older adults.

Abundant research has provided evidence that disruptions in the sleep-wake cycles of both humans and rodents can affect the deposition of beta-amyloid (Aß) in the brain ¹. Less time spent in REM sleep is associated with greater brain Aß, in rodent models ¹ and humans ². While some studies have shown that the Aß accumulation rate and cognitive function decline can occur simultaneously ³, other studies have demonstrated that the deposition of Aß can occur years before evidence of cognitive impairment ⁴ and is not always a predictor of  cognitive function ⁵.  Subjective data has associated excessive daytime sleepiness ⁶, and obstructive sleep apnea ⁷, with greater Aß accumulation over time.

Researchers tested the hypothesis ⁸ that initial baseline measures of non-rapid eye movement (NREM) sleep slow-wave activity (SWA) and sleep quality (efficiency) can predict the subsequent rates of Aβ accumulation in future years. By using objective sleep polysomnography (PSG) and electroencephalogram (EEG) researchers were able to establish baseline values of SWA, sleep efficiency, and the sleep stages of NREM and rapid eye movement (REM) in a cohort of 32 clinically normal, cognitively healthy older adults. Using (11C)PiB positron emission tomography (PET) imaging allowed the team to track the growth rate and accumulation of Aß protein in the brains of participants throughout the multi-year study, and to compare participants’ beta-amyloid levels to their sleep profiles. The mean duration follow-up was 3.7 years with an average of two to five PET scans per participant. Sleep efficiency was defined as actual time spent asleep, as opposed to lying sleepless in bed.

Results showed that reduced SLA and low sleep efficiency at baseline were both associated with accelerated rate of cortical Aß plaque deposition in participants. Those with low SWA at baseline experienced a significantly greater rate of cortical Aß accumulation compared to those with higher SWA (r=0.52, P=0.002).  More specifically, worse sleep efficiency and diminished low-frequency <1 Hz SWA during NREM sleep were associated with the rate of future Aß accumulation. These relationships were significant in that no other aspects of sleep beyond sleep efficiency, demonstrated such significant predictive associations. Furthermore, the relationships were strong when taking into account additional factors such as age, sex, and sleep apnea (p< 0.001)

PiB PET scans, which are sensitive markers of rates of future Aß increase, ⁹ are invasive, costly and have limited availability; thus, study results suggest sleep assessment as a possible non-invasive alternative. Researchers also suggest using EEG to assess NREM SWA, and EEG or wristwatch actigraphy to assess sleep efficiency. These are potentially non-invasive, repeatable, and safe options for quantifying the progression of Aß before cognitive symptoms of AD become evident. Sleep, when viewed as a biomarker of early Alzheimer’s disease (AD), it is a modifiable lifestyle factor; therefore, research focusing on middle-aged populations is highly recommended to determine whether sleep problems and evidence of AD pathology exist in this age group. Sleep deficiency, when detected early and treated, may be a potential preventative and therapeutic target for not only decreasing or controlling AD risk but also for delaying its onset of symptoms.

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 (2020).

Posted September 29, 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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