Alzheimer’s disease genetic risk and sleep phenotypes: association with more slow-waves and daytime sleepiness

Study ObjectivesSleep 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.MethodsWe 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.ResultsAD 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.ConclusionsThese 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.Statement of SignificanceWe show that the genetic liability for developing for Alzheimer’s disease (AD), as grasped over the entire genome using polygenic risk scores (PRS), is associated with sleep intensity and daytime sleepiness in healthy individuals devoid of sleep disorders and aged < 30 y, i.e. 30 to 60 years before typical onset of AD cognitive symptoms. Sleep features may be associated with AD liability in young adults, when current AD biomarkers are typically negative. The findings reinforce the notion that quantifying sleep alterations may be useful in assessing the risk for developing AD.