Sleep arousals are associated with the polygenic risk for developing Alzheimer's disease and with cognitive decline in healthy late middle-aged individuals

Objective: Sleep disturbances are increasingly recognized as early features of Alzheimer's disease (AD) neuropathology. In that context, spontaneous arousals during sleep have been associated with the burden of Amyloid beta in the brain of healthy late middle-aged individuals. Whether the heterogeneity of arousals during sleep may be related to the genetic risk of developing AD in young adults is not established. Likewise, whether arousals may be associated with cognitive decline is not known. Here, we evaluated the association between arousals, the genetic risk for developing AD and cognitive performance and cognitive decline in healthy young and late-middle-aged individuals. Methods: We classified spontaneous arousals using in-lab EEG recordings of sleep in 453 younger individuals (22+/-2.7y; 49 women) and 87 late middle-aged individuals (59.3+/-5.3y; 59 women) based on their association with sleep stage transitions and changes in muscle tone. We examined the associations between arousal types and the polygenic risk scores (PRS) for AD, cognitive performance at baseline and, in late middle-aged individuals, cognitive decline over 2 and 7 years. Results: The prevalence of arousals associated with sleep stage transition was higher in late middle-aged vs. younger individuals. Among these arousals, those with and without muscle tone increases were, respectively, associated with lower and higher PRS for AD in late middle-aged but not in younger individuals. In the late middle-aged individuals, transition arousals associated with and without muscle tone increases were, respectively, correlated with better and worse attentional performance at baseline, and lower and larger memory decline over 2 or 7 years. Conclusion: The heterogeneity in spontaneous arousals during sleep may reflect their physiological intensity or underlying neural activation, and may indicate vulnerability to AD in late middle-aged individuals. The findings may contribute to identifying early markers of neurodegenerative risk.