Chronic intermittent hypoxia-mediated cognitive dysfunction in ovariectomized rats

Obstructive sleep apnoea (OSA) is a prevalent cardiorespiratory disorder associated with significant neurocognitive consequences. Despite the higher prevalence of OSA in men, there is a strong association between OSA and Alzheimer's disease (AD), which disproportionately affects women. This study aimed to investigate the impact of chronic intermittent hypoxia (CIH), a hallmark of OSA, on cognitive function and AD markers in ovariectomized, female rats. At 8 weeks of age, 16 Sprague-Dawley rats underwent ovariectomy and were exposed to CIH for 26 weeks. Cognitive function was assessed using the Morris water maze, revealing significant deficits in spatial learning (P < 0.0001) and memory (P = 0.008) in CIH-exposed rats, compared to controls. Analysis of hippocampal tissue showed increased total tau protein (P = 0.0078), indicative of AD pathology. Additionally, CIH-exposed rats exhibited respiratory dysfunction characterized by increased frequency of apnoeas (P = 0.0328). These findings provide preclinical evidence of the association between OSA, cognitive decline and AD pathology in females, emphasizing the importance of sex-specific research in understanding and addressing these pathophysiological interconnections.