Pathways between OSA and cognitive decline in older women and men: a longitudinal population-based study

摘要 大约有570万美国人患有痴呆症。阿尔茨海默氏症占大多数病例。 美国痴呆症的患病率和影响不断上升，再加上缺乏有效的预防治疗， 治愈或延缓痴呆症的进展，促使人们迫切需要确定可改变的危险因素。一 可能是阻塞性睡眠呼吸暂停(OSA)。这种高度低估的和相应的睡眠障碍影响 至少24%的美国老年人。尽管新出现的证据表明阻塞性睡眠呼吸暂停与认知障碍和 痴呆症发病率，现有报告没有充分研究潜在的关键混杂因素以及 可能影响这种关系的生物相关生物标志物。此外，很少有研究聚焦于 呼吸道正压治疗对阻塞性睡眠呼吸暂停综合征发病风险的影响 痴呆症。来自调查人员的最新数据表明，阿尔茨海默氏症的发病率在 与非PAP用户相比，接受PAP治疗的OSA患者的联邦医疗保险受益人。这表明一种 在受阻塞性睡眠呼吸暂停综合征影响的老年人中，使用PAP对痴呆风险的保护作用。来自调查人员的数据还包括 在阻塞性睡眠呼吸暂停综合征的治疗中表现出性别差异。女性对阿尔茨海默氏症和阻塞性睡眠呼吸暂停综合征的易感性 治疗不足进一步突出了OSA是否是阿尔茨海默氏症的危险因素的问题。 因此，本项目的总体目标是评估OSA和PAP对以下方面的纵向影响 老年女性和男性的认知结果，并解构 病理性睡眠和痴呆症。这将通过利用客观的认知、睡眠、健康、 以及从健康和退休研究中每两年收集一次的生物标志物数据。来自于此的数据 具有全国代表性的多种族老年人纵向队列将与医疗保险相协调 声明数据以创建唯一适合于解决不可行的关键问题的大型数据集 以前瞻性的方式进行调查的成本很高。这项研究的发现将为睡眠提供新的见解-- 基于降低老年女性和男性认知发病率的目标；提供更有针对性的随机临床 试验；并促进努力确定最有可能从评估和治疗中受益的老年人 睡眠障碍。

ABSTRACT Approximately 5.7 million Americans have dementia. Alzheimer’s dementia accounts for the majority of cases. The rising prevalence and impact of dementia in the US, coupled with a lack of effective treatments to prevent, cure, or slow dementia progression, have galvanized an urgent need to identify modifiable risk factors. One may be obstructive sleep apnea (OSA). This highly underdiagnosed and consequential sleep disorder affects at least 24% of older Americans. Although emerging evidence has linked OSA to cognitive impairment and dementia incidence, existing reports have insufficiently examined potential key confounders as well as biologically relevant biomarkers that may influence this relationship. Furthermore, little research has focused on the effects of OSA treatment with positive airway pressure therapy (PAP) on risk for development of dementia. Recent data from the investigators demonstrate a lower incidence of Alzheimer’s dementia among Medicare beneficiaries with OSA who are treated with PAP, compared to non-PAP users. This suggests a protective role for PAP use on dementia risk in OSA-affected older adults. Data from the investigators also has shown sex disparities in OSA treatment. The vulnerability of women to both Alzheimer’s dementia and OSA under-treatment further highlights the question of whether OSA is a risk factor for Alzheimer’s dementia. Therefore, the overarching goal of this project is to assess the longitudinal impact of OSA and PAP on cognitive outcomes among older women and men, and to deconstruct unexplored pathways between pathological sleep and dementia. This will be accomplished by leveraging objective cognitive, sleep, health, and biomarker data that are collected biennially from the Health and Retirement Study. Data from this nationally representative, multi-ethnic longitudinal cohort of older adults will be harmonized with Medicare claims data to create a large dataset uniquely suited to address critical questions that would be unfeasibly expensive to investigate in a prospective manner. Findings from this study will provide new insight into sleep- based targets to reduce cognitive morbidity of older women and men; inform more targeted randomized clinical trials; and foster efforts to identify older individuals most likely to benefit from evaluation and treatment for sleep disorders.