Sleep · May 22, 2026

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

By Mortazavi N, Zubkov M, Chylinski D et al.

STUDY OBJECTIVES: Sleep disturbances are increasingly recognized as early features of Alzheimer's disease (AD) neuropathology. Specifically, spontaneous arousals during sleep have been associated with the burden of Amyloid beta in the brain of healthy late middle-aged individuals. However, it remains unclear whether heterogeneity of arousals relates to genetic risk for AD in younger adults or to cognitive change later in life. Here, we evaluated the association between arousals, polygenic risk scores (PRS) for AD, and cognitive performance and change in healthy young and late-middle-aged individuals. METHODS: We classified spontaneous arousals using in-lab EEG sleep recordings 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, AD-PRS, baseline cognitive performance and, in late middle-aged individuals, cognitive change over 2 and 7 years. RESULTS: The prevalence of arousals associated with sleep stage transition was higher in late middle-aged vs. younger individuals. In late middle-aged but not younger individuals, transition arousals with muscle tone increases correlated with lower AD-PRS, better attentional performance and lower memory change over follow-ups, whereas transition arousals without muscle tone increases were linked to higher AD-PRS, poorer baseline attention, and greater memory change across follow-up periods. CONCLUSIONS: 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 help identify early markers of neurodegenerative risk. Statement of Significance Sleep arousals are often considered disruptive, yet their physiological diversity may provide key insights into brain health. This study shows that distinct subtypes of spontaneous sleep arousals are differentially associated with genetic vulnerability to Alzheimer's disease (AD) and future cognitive change in healthy late middle-aged adults. Arousals linked to sleep stage transitions without muscle activation were related to higher polygenic risk for AD and greater memory change, whereas those with muscle tone increases showed the opposite pattern. These results suggest that subtle variations in sleep microstructure reflect neurobiological vulnerability to AD before symptoms appear. Identifying electrophysiological markers tied to genetic risk and cognition highlights the potential of sleep-based biomarkers for early neurodegenerative detection.

doi.org/10.1093/sleep/zsag143 Open access, accepted manuscript PubMed 42171655 Biomarkers