Slow wave–spindle coupling during deep sleep is selectively linked to Plasma Amyloid-β levels in Older Adults

Abstract Background Slow wave activity, the signature of deep/slow wave sleep, has consistently been linked to amyloid-beta (Aβ), a biomarker of Alzheimer’s disease. Less is known about how Aβ relates to specific microstructural processes within slow wave sleep, such as the coupling of slow waves (SW) and sleep spindles. Although better SW–spindle coupling has been associated with younger age, increased memory performance, and less brain atrophy, its relationship with Aβ remains poorly understood, particularly due to a lack of research in cognitively impaired older adults. Here, we investigate the association between SW–spindle coupling and Aβ in both cognitively normal and cognitively impaired older individuals. Additionally, we examine how an acoustic stimulation intervention known to boost slow wave sleep affects the link between SW–spindle coupling and Aβ. Methods Forty-seven older adults (agemean = 70.5 (0.68)), ranging from cognitively impaired to cognitively healthy, completed one adaptation and one baseline night. A subsample (n = 39, agemean = 70.5 (0.74)) additionally underwent a three-night acoustic stimulation intervention designed to boost slow wave activity. Blood samples post-baseline and post-intervention were analyzed for Aβ 1–42/1-40-ratio. Results Regardless of cognitive functioning, SW–spindle coupling was the best predictor for baseline Aβ, better than slow wave activity, age or cognitive functioning. Specifically, more favorable Aβ-levels were linked to a SW–spindle coupling physiology resembling a younger brain. While intervention-induced increases in slow wave activity were linked to a beneficial Aβ-response across all cognitive levels, intervention-induced increases in SW–spindle coupling benefited Aβ-response exclusively in cognitively impaired individuals. Conclusions Our results suggest a link between SW–spindle coupling and Aβ going beyond slow wave activity. This hints towards a potential specific function of SW–spindle coupling related to the early pathophysiology of Alzheimer’s disease.