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，人们努力确定“可采取行动的”风险因素，如果及早确定和解决， 预防认知能力下降和ADRD发作的潜力。阻塞性睡眠呼吸暂停（OSA）与 认知能力下降和ADRD的风险，尤其是老年人。由于有有效的治疗方法， 条件（例如，持续气道正压通气[CPAP]），已被证明非常有效 坚持使用OSA可能是降低ADRD风险的理想靶点。在这项研究中，我们建议 描述OSA治疗（特别是CPAP）与认知功能下降和ADRD之间的相关性 在两个具有全国代表性的由NIA资助的美国老年人队列中进行了14年的随访（2010-2024）： 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在ADRD的高风险人群中不同（例如， 少数民族/种族、高龄、心血管风险因素/疾病等）为了确定种群 其中治疗最有可能产生效果，并且OSA治疗方法可以在组中优化 而不是受益。HRS和NHATS都包括全国代表性样本，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OSA的诊断和治疗。该研究将采用创新方法， 统一数据集，并将实现三个具体目标。目的1将是确定OSA与 2010-2024年的认知轨迹和ADRD事件，并检查OSA是否与其他ADRD相互作用 认知能力下降和ADRD风险的风险因素。目标2将是确定， OSA，CPAP是否与2010-2024年更好的认知结果相关。具体来说，我们将研究 a）接受CPAP（与未治疗相比）是否与较慢的认知衰退和较低的 ADRD的风险，B）在接受治疗的患者中，开始CPAP是否与认知下降的减缓相关 开始治疗前后ADRD的风险较低，以及c）这些相关性是否因CPAP水平而异 坚持。最后，目标3将检查目标2中发现的相关性是否会在已知的ADRD风险中存在差异 因素如果我们发现解决OSA在减缓认知能力下降/预防ADRD方面特别有效， 特别是在高危人群中，那么我们的研究结果将有助于我们了解OSA的发病机制。 在人群中进行治疗，并有助于开发在这些人群中治疗OSA的计划， 风险此外，它将为美国遏制ADRD负担的努力提供信息，并大大有助于痴呆症 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.