Causal relationship between Alzheimer’s disease and obstructive sleep apnoea: Insights from a biomechanics-oriented bidirectional mendelian randomization study

Background: The latest observational studies revealed a possible association between Alzheimer ‘s disease (AD) and obstructive sleep apnoea (OSA). In AD, the accumulation of amyloid-beta plaques and tau tangles disrupts the normal structure and function of neurons in the brain. These pathological changes can affect the mechanical properties of neural tissues, altering their elasticity and stiffness. Such alterations might extend to the neural circuits responsible for regulating sleep and respiration, potentially influencing the occurrence of OSA. We used bidirectional Mendelian randomization approach to analyze causalities between OSA, its typical symptoms (snoring and daytime sleepiness) and AD in European populations. Methods: Single nucleotide polymorphisms of AD and OSA, snoring, daytime dozing were selected as instrumental variables. Preliminary MR analysis was inverse-variance weighted (IVW) method. The Cochran Q test, MR-Egger analysis, ‘leave-one-out’ test were used to verify the data robustness. Results were adjusted for Bonferroni correction thresholds. Results: Results from IVW demonstrated a suggestive correlation between AD and higher risks of sleep apnoea (OR 1.0008, 95%CI 1.0000–1.0016, p = 0.044) after Bonferroni correction. However, reverse MR analysis showed no association of genetically primed sleep apnoea towards AD (p = 0.294). No causal effect was detected between genetic AD and snoring, daytime dozing. From a biomechanical perspective, the positive correlation between AD and increased risk of sleep apnoea could be due to the fact that the structural changes in the brain caused by AD might lead to changes in the biomechanical forces exerted on the brainstem regions that control breathing during sleep. Conclusions: The findings of the MR study support that AD might increase the risk of OSA. Therefore, individuals with AD should strengthen sleep monitoring, sleep hygiene and develop a regular sleep-wake pattern. Understanding these underlying biomechanical mechanisms could provide valuable insights for developing targeted interventions to mitigate the risk of OSA in AD patients and potentially improve their overall sleep quality and disease management.