Is Obstructive Sleep Apnea Important in the Development of Alzheimer's Disease

项目摘要 衰老是阻塞性睡眠呼吸暂停（OSA）发展的已知危险因素，尽管潜在的 机制只是最近才被理解。OSA与阿尔茨海默病有关， 流行病学研究以及具有共同的遗传联系。了若干机制 提出包括氧化应激和淀粉样蛋白和tau蛋白沉积，这可能有助于观察到的联系。 最近的著名出版物已经强调了睡眠中断对阿尔茨海默氏症风险的潜在影响。我们 已经清楚地观察到睡眠依赖性记忆巩固的损害，即使是轻度OSA， 制定了强有力的方法，以严格的方式评估这些结果。最近的证据表明 老年人中的OSA可能与年轻人中的OSA有所不同， 相对独特的潜在机制。我们最近发布并验证了允许 使用微创方法评估OSA的病理生理学基础， 临床上可进行内分型。我们最近还发现，OSA患者的亚组对 并且可以基于OSA的潜在病理生理学来预测。我们计划研究和进一步 通过评估氧气治疗对OSA患者的影响来验证我们的模型， 老年痴呆症我们有一个强大的神经认知结果面板，并有令人兴奋的初步数据 显示了海马记忆中观察到的一些损伤的可逆性。而且我们现在 与影像学和神经心理学专家合作，他们将帮助我们定义可靠的结果指标 使用MRI和PET扫描（例如体积分析、淀粉样蛋白、tau）。最终，我们希望这个应用程序 将为机械比较有效性试验奠定基础， 标准治疗选择阻塞性睡眠呼吸暂停症患者，努力防止阿尔茨海默病的发展。 然而，无论拟议工作的结果如何，我们都将获得对机制的重要见解， 对患有OSA的老年人进行最佳护理。

Project Abstract Aging is a known risk factor for the development of obstructive sleep apnea (OSA), although the underlying mechanisms are only recently being understood. OSA is associated with Alzheimer’s disease in epidemiological studies as well as having common genetic links. A number of mechanisms have been proposed including oxidative stress and amyloid and tau deposition which may contribute to the observed link. Recent prominent publications have hi-lighted the potential impact of sleep disruption on Alzheimer’s risk. We have clearly observed impairment in sleep-dependent memory consolidation even with mild OSA and have developed robust methods to assess these outcomes in a rigorous manner. Recent evidence suggests that OSA in older individuals may be a somewhat different disease than OSA in younger individuals, based on relatively unique underlying mechanisms. We have recently published and validated techniques allowing the assessment of the pathophysiology underlying OSA using minimally invasive methods making disease endotyping clinically accessible. We have also recently found subgroups of OSA patients who respond well to oxygen and can be predicted based on the underlying pathophysiology of OSA. We plan to study and further validate our model by assessing the impact of oxygen therapy in OSA patients who are at risk of developing Alzheimer’s disease. We have a robust panel of neurocognitive outcomes and have exciting preliminary data showing reversibility of some of the observed impairment in hippocampal memory. Moreover we are now working with expert imaging and neuropsychology collaborators who will help us define robust outcome metrics using MRI and PET scanning (e.g. volumetric analyses, amyloid, tau). Ultimately we hope that this application will lay the groundwork for a mechanistic comparative effectiveness trial whereby we can compare oxygen with standard therapy for select OSA patients in an effort to prevent the development of Alzheimer’s disease. Regardless of the results of the proposed work however we will gain major insights into the mechanisms and optimal care of elderly people with OSA.