Alzheimer’s disease genetic risk and sleep phenotypes in healthy young men: association with more slow waves and daytime sleepiness

Abstract

Study Objectives Sleep disturbances and genetic variants have been identified as risk factors for Alzheimer’s disease. Our goal was to assess whether genome-wide polygenic risk scores (PRS) for AD associate with sleep phenotypes in young adults, decades before typical AD symptom onset. Methods We computed whole-genome Polygenic Risk Scores (PRS) for AD and extensively phenotyped sleep under different sleep conditions, including baseline sleep, recovery sleep following sleep deprivation and extended sleep opportunity, in a carefully selected homogenous sample of healthy 363 young men (22.1 y ± 2.7) devoid of sleep and cognitive disorders. Results AD PRS was associated with more slow wave energy, i.e. the cumulated power in the 0.5-4 Hz EEG band, a marker of sleep need, during habitual sleep and following sleep loss, and potentially with large slow wave sleep rebound following sleep deprivation. Furthermore, higher AD PRS was correlated with higher habitual daytime sleepiness. Conclusions These results imply that sleep features may be associated with AD liability in young adults, when current AD biomarkers are typically negative, and the notion that quantifying sleep alterations may be useful in assessing the risk for developing AD.

“Genetic and chemical disruption of Amyloid Precursor Protein processing impairs zebrafish sleep maintenance”

“…For example, patients with Alzheimer’s Disease (AD) have reductions in the amount of rapid eye movement (REM) and non-REM (NREM) sleep, an increase in the amount of wakefulness, more sleep fragmentation (Allen et al, 1987; Loewenstein et al, 1982; Prinz et al, 1982; Vitiello et al, 1990), and electroencephalographic (EEG) alterations in sleep features (D’Atri et al, 2021), yet these symptoms occur many years before cognitive decline and cell death (Sterniczuk et al, 2013). Healthy young men (∼22 years old) with high genome-wide polygenic risk scores for AD have higher slow wave energy during sleep (Muto et al, 2021). Similarly, both excessive daytime sleepiness and high sleep fragmentation in cognitively normal adults are associated with increased risk of Aβ deposition (Spira et al, 2018) and AD, respectively (Lim et al, 2013).…”

“…Consistent with this, some transgenic AD mouse models that overproduce Aβ display sleep disruptions prior to plaque formation, even without evident neuronal loss [5][6][7][8][9][10][11] . Recently, human studies have found that harbouring a high genetic risk for AD correlates with sleep changes, such as increased sleep rebound following sleep loss, even in young adults 12 . These observations suggest that there may be underlying early biological processes important for sleep regulation that are governed by AD susceptibility genes and contribute to disease progression.…”

Association between sleep slow-wave activity and in-vivo estimates of myelin in healthy young men

“…A total of 364 young healthy men were initially recruited as part of a larger project assessing the genetic background of sleep regulation (see also Berthomier et al., 2020 ; Muto et al., 2021 ). Within that context, a homogeneous sample with respect to demographic variables (age [18–31], gender [male], ethnicity [Caucasian]) and health status was recruited.…”

“…Our sample of participants was recruited in the context of a project that aimed to assess the genetic background of sleep regulation (e.g. Muto et al., 2021 ) and is thus only composed of men, mainly university students. Women have been shown to present higher sleep SWA than men, and this difference seems to be present in adults of various ages ( Carrier et al., 2001 ; Dijk, 2006 ; Dijk et al., 1989 ).…”

pyActigraphy: Open-source python package for actigraphy data visualization and analysis

“…with multiple algorithms [58,59] or assess sleep fragmentation via transition state probability [60].…”