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

项目摘要 衰老是发生阻塞性睡眠呼吸暂停(OSA)的已知危险因素，尽管潜在的 机制直到最近才被理解。阻塞性睡眠呼吸暂停综合征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。一系列机制已经被 建议包括氧化应激、淀粉样蛋白和tau沉积，这可能有助于观察到的联系。 最近著名的出版物都强调了睡眠障碍对阿尔茨海默氏症风险的潜在影响。我们 即使患有轻度阻塞性睡眠呼吸暂停，也清楚地观察到睡眠依赖记忆巩固方面的障碍，并有 制定了强有力的方法，以严格评估这些结果。最近的证据表明 老年人的OSA可能与年轻人的OSA疾病略有不同，基于 相对独特的潜在机制。我们最近发布并验证了一些技术，允许 应用微创方法评估阻塞性睡眠呼吸暂停的病理生理学基础 内切分型可在临床上使用。我们最近还发现OSA患者的亚群对 氧气，并可根据阻塞性睡眠呼吸暂停的潜在病理生理学进行预测。我们计划研究并进一步 通过评估氧疗对有发展风险的OSA患者的影响来验证我们的模型 阿尔茨海默氏症。我们有一个强大的神经认知结果小组，并有令人兴奋的初步数据 显示了一些观察到的海马体记忆损害的可逆性。此外，我们现在是 与影像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(例如容量分析、淀粉样蛋白、tau)。最终，我们希望该应用程序 将为一项机械效率比较试验奠定基础，我们可以用氧气和 为选定的阻塞性睡眠呼吸暂停综合征患者提供标准治疗，以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，我们都将对这些机制和 为患有阻塞性睡眠呼吸暂停综合症的老年人提供最佳护理。

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.