Inefficient Sleep May Forecast Risk of Alzheimer Disease

Reduced slow-wave activity during non-rapid eye movement sleep and low sleep efficiency, both of which sleep assessments can measure, may be part of biomarkers that forecast the rate of cortical β-amyloid deposition in the brain.

Reduced slow-wave activity (SWA) during non-rapid eye movement (NREM) sleep and low sleep efficiency are both associated with an accelerated rate of future β-amyloid (Aβ) accumulation, and therefore sleep assessment could be an effective, non-invasive alternative to a PiB positron emission tomography (PET) scan before cognitive symptoms of Alzheimer disease (AD) appear, a longitudinal cohort study published in Current Biology found.

The researchers assessed a cohort of 32 adults (23 women, mean age of 75.5, standard deviation (SD)=4.3 years) using overnight polysomnography recording and repeat PET brain scan assessments of Aβ. They administered full-head electroencephalogram (EEG) polysomnography (PSG) to quantify SWA and recorded the subjects’ sleep efficiency (total amount of sleep as a percentage of total time in bed) and NREM and rapid-eye movement (REM) sleep stages.

Each participant underwent a mean total number of 2.6 PET scans (including the first scan and follow-up scans, range of 2 to 5), at a mean duration of follow-up assessment of 3.7 years (SD=2.4 years), so the researchers could measure longitudinal change in Aβ accumulation.

The researchers found that individuals with lower proportions of <1 Hz SWA at baseline experienced a significantly greater rate of cortical Aβ accumulation than those who had higher proportions of <1 Hz SWA (r = -0.52, P =.002) and the baseline measure of Aβ was associated with Aβ change (r = 0.80, P < .001). Sleep efficiency was negatively associated with baseline Aβ burden (r = -0.43, P =.01).

The investigators noted that the study results cannot prove that impaired sleep causes Aβ plaque accumulation because most of the study subjects already had substantial Aβ deposition at baseline, they treated PiB DVR as a continuous variable and they could not separate subjects according to initial Aβ status.

“In conclusion, the current data support the hypothesis that objective markers of human sleep are statistically sensitive in forecasting the longitudinal trajectory of cortical Aβ plaque deposition,” the researchers said. “Alongside other promising markers, the assessment of NREM SWA with EEG, and sleep efficiency measured using EEG or wristwatch actigraphy, could represent part of a set of potentially non-invasive, repeatable, and safe tools for quantification of Aβ pathological progression, before cognitive symptoms of AD.”

Disclosure: Several study authors declared industry affiliations. Please see the original reference for a full list of authors’ disclosures.


Winer JR, Mander BA, Kumar S, et al. Sleep disturbance forecasts β-amyloid accumulation across subsequent years. Curr Bio. 2020;30(21):4291-4298 doi:10.1016/j.cub.2020.08.017