Sleep apnea treatment and risk for cognitive decline and Alzheimers disease

摘要 到2050年，阿尔茨海默病和相关痴呆症(ADRD)的患病率预计将增加四倍。 因此，必须努力找出“可采取行动”的风险因素，如果及早发现并加以解决，就会产生 预防认知功能减退和ADRD发病的可能性。阻塞性睡眠呼吸暂停(OSA)与 认知衰退和ADRD的风险，特别是在老年人中。因为有有效的治疗方法可用于 已证明有效的条件(如持续正压[CPAP]) 如果坚持使用，OSA可能是降低ADRD风险的理想目标。在这项研究中，我们建议 描述阻塞性睡眠呼吸暂停(OSA)治疗(特别是CPAP)与认知衰退和UP上的ADRD之间的关系 对NIA资助的两个具有全国代表性的美国老年人队列进行了14年(2010-2024年)的随访： 健康与退休研究(HRS)和国家健康与老龄化趋势研究(NHATS)。我们还打算 为了确定OSA治疗对认知的影响是否与ADRD风险较高的人不同(例如， 少数民族种族/民族、高龄、心血管危险因素/疾病等)为了识别种群 其中治疗最有可能产生效果，以及OSA治疗可以分组优化的方法 而不是受益。HRS和NHATS都包括具有全国代表性的样本，具有重复性能- 基于认知测量来表征认知表现轨迹和ADRD，以及与 医疗保险要求确定阻塞性睡眠呼吸暂停综合征的诊断和治疗。这项研究将使用创新的方法 统一数据集，并将解决三个具体目标。目标1将确定阻塞性睡眠呼吸暂停综合征与 2010-2024年认知轨迹和事件ADRD，并检查OSA是否与其他ADRD相互作用 与认知能力下降和ADRD风险有关的风险因素。目标2将确定，在患有 阻塞性睡眠呼吸暂停综合症，CPAP是否与2010-2024年更好的认知结果相关。具体来说，我们将审查 A)接受CPAP治疗(与不接受治疗相比)是否与认知功能下降较慢和较低有关 ADRD的风险，b)在接受治疗的患者中，CPAP的启动是否与认知衰退的减缓有关 以及启动前后ADRD的风险降低，以及c)这些关联是否随CPAP水平的不同而不同 坚持不懈。最后，目标3将检查在目标2中发现的关联是否会在已知的ADRD风险中有所不同 各种因素。如果我们发现解决阻塞性睡眠呼吸暂停综合症在减缓认知衰退/预防ADRD方面特别有效， 尤其是在高危人群中，我们的研究结果将帮助我们理解阻塞性睡眠呼吸暂停综合征 在人群中接受治疗，并为制定最大限度地治疗这些人群中的阻塞性睡眠呼吸暂停综合征的计划做出贡献 风险。此外，它将为在美国遏制ADRD负担的努力提供信息，并大大促进痴呆症的发生 预防工作。

ABSTRACT The prevalence of Alzheimer’s disease and related dementias (ADRD) is expected to increase four-fold by 2050. Consequently, there are efforts to identify “actionable” risk factors, that if identified and addressed early, have the potential to prevent cognitive decline and onset of ADRD. Obstructive sleep apnea (OSA) is associated with risk of cognitive decline and ADRD, particularly among older adults. As effective treatments are available for the condition (e.g., Continuous Positive Airway Pressure [CPAP]) that are demonstrated to be highly efficacious when used adherently, OSA may be an ideal target for ADRD risk reduction. In this study, we propose to characterize associations between OSA treatment (specifically CPAP) and cognitive decline and ADRD over up to 14 years of follow-up (2010-2024) in two nationally representative NIA-funded cohorts of U.S. older adults: the Health and Retirement Study (HRS), and National Health and Aging Trends Study (NHATS). We also intend to determine whether the effects of OSA treatment on cognition differ in those at higher risk for ADRD (e.g., minority race/ethnicity, advanced age, cardiovascular risk factors/disease, etc.) in order to identify populations among whom treatment is most likely to yield effects and ways OSA treatments could be optimized in groups not benefiting. Both HRS and NHATS include nationally representative samples, have repeated performance- based cognitive measures to characterize cognitive performance trajectories and ADRD, and linkages to Medicare claims for ascertainment of OSA diagnosis and treatment. The study will use innovative methods to harmonize datasets and will address three specific aims. Aim 1 will be to determine the association of OSA with cognitive trajectories and incident ADRD from 2010-2024, and examine whether OSA interacts with other ADRD risk factors with regard to cognitive decline and ADRD risk. Aim 2 will be to determine, among individuals with OSA, whether CPAP is associated with better cognitive outcomes from 2010-2024. Specifically, we will examine whether a) receipt of CPAP (compared to no treatment) is associated with slower cognitive decline and lower risk for ADRD, b) among those treated whether initiation of CPAP is associated with a slowing of cognitive decline and lower risk for ADRD before and after initiation, and c) whether these associations vary across levels of CPAP adherence. Finally, Aim 3 will examine whether associations found in Aim 2 will differ across known ADRD risk factors. If we find that addressing OSA is particularly effective in slowing cognitive decline/preventing ADRD, especially in high-risk groups, then our study’s results will help us understand the means by which OSA can be treated in the population and contribute to development of programs to treat OSA in these populations at greatest risk. Further, it will inform efforts to curb the burden of ADRD in the U.S. and contribute substantially to dementia prevention efforts.