Impaired sleep was associated with a higher rate of future beta amyloid accumulation, a potential catalyst of Alzheimer disease onset, according to study findings.
In examining risk of Alzheimer disease (AD), the accumulation of beta amyloid (β-amyloid), which is a naturally occurring protein that clumps together to form plaques within neurons, has been indicated as the primary catalyst driving AD pathogenesis, based on the amyloid hypothesis.
When distinguishing what drives β-amyloid accumulation, researchers of a study published in Current Biology note that experimental sleep-wake disruption in rodents and humans causally determines the dynamics behind this protein. This finding has contributed to a hypothesis that pinpoints impaired sleep structure and physiology as prospective biomarkers that influence the progression of β-amyloid accumulation over time.
Researchers sought to test this hypothesis by assessing baseline measures of non-rapid eye movement (NREM) sleep slow-wave activity (SWA) and sleep quality (efficiency). In the study, 32 healthy older adults (mean [SD] age, 75.5 [4.3] years), part of the Berkeley Aging Cohort Study, spent an 8-hour night of sleep in the lab of study author Matthew Walker, neuroscientist at the University of California, Berkeley (UC Berkeley). Each participant additionally underwent polysomnography, a battery of tests that record brain waves, heart rate, blood-oxygen levels, and other physiological measures of sleep quality.
Across the multiyear study, researchers periodically tracked the growth rate of β-amyloid in each participant's brain via PET scans and then compared these levels with one’s sleep profile.
In the study findings, both the proportion of NREM SWA below 1 Hz and the measurement of sleep quality predicted the speed, or slope, of subsequent β-amyloid deposition over time, with these associations remaining robust after stratifying for additional cofactors of interest, such as age, sex, and sleep apnea. The researchers note that measures were specific; no other macro- or microphysiological architecture metrics of sleep were as sensitive.
"Rather than waiting for someone to develop dementia many years down the road, we are able to assess how sleep quality predicts changes in β-amyloid plaques across multiple timepoints," said lead study author Joseph Winer, PhD student in the Center for Human Sleep Science at UC Berkeley. “In doing so, we can measure how quickly this toxic protein accumulates in the brain over time, which can indicate the beginning of AD.”
In addressing next steps, Walker and Winer note they will look into assessing the impact of an intervention that would boost the quality of sleep among study participants who are at high risk of developing AD. "Our hope is that if we intervene, then in 3 or 4 years, the buildup is no longer where we thought it would be because we improved their sleep," concluded Winer.
Winer JR, Mander BA, Kumar S, et al. Sleep disturbance forecasts β-amyloid accumulation across subsequent years. Published online September 3, 2020. Curr Biol. doi:10.1016/j.cub.2020.08.017