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) 发生的一个已知危险因素，尽管潜在的因素 机制直到最近才被了解。 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。多项机制已出台 建议包括氧化应激以及淀粉样蛋白和 tau 蛋白沉积，这可能有助于观察到的联系。 最近的著名出版物强调了睡眠中断对阿尔茨海默病风险的潜在影响。我们 即使患有轻度 OSA，也可以清楚地观察到睡眠依赖性记忆巩固受损，并且 制定了稳健的方法来严格评估这些结果。最近的证据表明 老年人的 OSA 可能与年轻人的 OSA 是一种有些不同的疾病，基于 相对独特的底层机制。我们最近发布并验证了技术，允许 使用微创方法评估 OSA 的病理生理学 临床上可进行内分型。我们最近还发现 OSA 患者亚组对以下药物反应良好 氧，并且可以根据 OSA 的潜在病理生理学进行预测。我们计划学习并进一步 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 阿尔茨海默病。我们拥有强大的神经认知结果面板和令人兴奋的初步数据 显示一些观察到的海马记忆损伤的可逆性。而且我们现在 与专家成像和神经心理学合作者合作，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，我们可以将氧气与 针对特定 OSA 患者的标准治疗，以预防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和机制的重要见解。 患有 OSA 的老年人的最佳护理。

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.