Mediating role of obstructive sleep apnea in altering slow-wave activity and elevating Alzheimer's disease risk: Pilot study from a northern Taiwan cohort

Objectives: Obstructive sleep apnea is associated with alterations in slow-wave activity during sleep, potentially increasing the risk of Alzheimer's disease. This study investigated the associations between obstructive sleep apnea manifestations such as respiratory events, hypoxia, arousal, slow-wave patterns, and neurochemical biomarker levels. Methods: Individuals with suspected obstructive sleep apnea underwent polysomnography. Sleep disorder indices, oxygen metrics, and slow-wave activity data were obtained from the polysomnography, and blood samples were taken the following morning to determine the plasma levels of total tau (T-Tau) and amyloid beta-peptide 42 (Aβ₄₂) by using an ultrasensitive immunomagnetic reduction assay. Subsequently, the participants were categorized into groups with low and high Alzheimer's disease risk on the basis of their computed product Aβ₄₂ × T-Tau. Intergroup differences and the associations and mediation effects between sleep-related parameters and neurochemical biomarkers were analyzed. Results: Forty-two participants were enrolled, with 21 assigned to each of the low- and high-risk groups. High-risk individuals had a higher apnea–hypopnea index, oxygen desaturation index (≥3%, ODI-3%), fraction of total sleep time with oxygen desaturation (SpO_2-90% _TST), and arousal index and greater peak-to-peak amplitude and slope in slow-wave activity, with a correspondingly shorter duration, than did low-risk individuals. Furthermore, indices such as the apnea–hypopnea index, ODI-3% and SpO_2-90% _TST were found to indirectly affect slow-wave activity, thereby raising the Aβ₄₂ × T-Tau level. Conclusions: Obstructive sleep apnea manifestations, such as respiratory events and hypoxia, may influence slow-wave sleep activity (functioning as intermediaries) and may be linked to elevated neurochemical biomarker levels. However, a longitudinal study is necessary to determine causal relationships among these factors. Statement of significance: This research aims to bridge gaps in understanding how obstructive sleep apnea is associated with an elevated risk of Alzheimer's disease, providing valuable knowledge for sleep and cognitive health.