Pilot Project: Intermittent Hypoxia in Alzheimer's Disease

Sleep disturbances are a common early symptom of neurodegenerative disease, including Alzheimer’s disease (AD), frontotemporal dementia, Lewy body and Parkinson disease dementia, and vascular contributions to cognitive impairment and dementia (VCID) (Guarnieri and Sorbi, 2015). Patients with obstructive sleep apnea have swings in blood pressure and heart rate associated with hypoxaemia that causes endothelial dysfunction and inflammation (Bokinsky et al., 1995; Yokoe et al., 2003). In autopsy tissue, aged patients with sleep apnea have increased microinfarcts, neuroinflammation and neuronal loss compared to the patients who did not have a recorded history of sleep apnea (Gelber et al., 2015). The overall prevalence of sleep-disordered breathing is high in the adult population affecting an estimated 10% -20% of adults in the United States. The prevalence is even greater in the elderly where it is estimated that 30 - 80% of aged population has some degree of sleep- disordered breathing (Osorio et al., 2015)(Roepke and Ancoli-Israel, 2010), with obstructive sleep apnea accounting for the majority of the sleep-disordered breathing cases. The clinical and epidemiological data clearly support a link between sleep-disordered breathing and age- related cognitive decline and dementia (Ju et al., 2013; Abner et al., 2015; Gelber et al., 2015; Lucey and Holtzman, 2015; Osorio et al., 2015). Yet, there has been very little experimental research directed at understanding the mechanism associated with this correlative link between sleep-disordered breathing and the increased risk for dementia. This is a critically important understudied area because there are clearly multiple potential mechanisms by which sleep-disordered breathing could be negatively affecting brain health. Sleep- disordered breathing is most common in patients with other risk factors for dementia, such as obesity and metabolic disorder. Therefore, we do not know if it is the sleep-disordered breathing or the metabolic syndrome which is the critical component that accelerates the onset of cognitive decline. Sleep apnea is treated with the continuous positive airway pressure (CPAP), and CPAP treatment has recently been shown to delay the age of onset of mild cognitive impairment (MCI) (Osorio et al., 2015) . While, CPAP treatment was found to slow the age of onset of MCI, the authors of the study noted that other factors such as “greater compliance with health advice” could be a cofounding variable (Osorio et al., 2015). Our study will be the first to experimentally explore the link between the effect of intermittent hypoxia (a model of sleep apnea) and Alzheimer’s disease related pathology.