San Diego State University/University of California San Diego, Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
Alzheimers Res Ther. 2024 May 9;16(1):102. doi: 10.1186/s13195-024-01446-3.
Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk.
Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined.
Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers.
Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.
阻塞性睡眠呼吸暂停（OSA）会增加认知能力下降和阿尔茨海默病（AD）的风险。虽然潜在机制尚不清楚，但 OSA 期间的低氧血症与认知障碍有关。REM 睡眠期间的 OSA 通常比非快速眼动（NREM）睡眠期间更严重，但 REM 与 NREM 睡眠期间氧合血红蛋白饱和度下降对记忆的相对影响尚未完全描述。在这里，我们研究了 OSA 以及 AD 风险因素的调节作用对具有较高 AD 风险的中年和老年人样本中言语记忆的影响。
81 名成年人（平均年龄：61.7±6.0 岁，62%女性，32%载脂蛋白 E ε4 等位基因（APOE4）携带者，70%有 AD 家族史）接受了临床多导睡眠图检查，包括 OSA 评估。OSA 特征在总睡眠、NREM 睡眠和 REM 睡眠中得出。还计算了 OSA 特征的 REM-NREM 比值。使用 Rey 听觉言语学习测试（RAVLT）评估言语记忆。在调整性别、年龄、评估时间、教育年限、体重指数（BMI）和 APOE4 状态或 AD 家族史后，使用多元回归模型评估 OSA 特征与 RAVLT 评分之间的关系。研究了 OSA 特征对 RAVLT 表现的显著主要影响以及 AD 风险因素（即性别、年龄、APOE4 状态和 AD 家族史）的调节作用。
REM 睡眠期间的呼吸暂停低通气指数（AHI）、呼吸紊乱指数（RDI）和氧合血红蛋白饱和度下降指数（ODI）与 RAVLT 总学习和长时延迟回忆呈负相关。此外，AHI、RDI 和 ODI 的 REM-NREM 比值更大（即 REM 中发生的事件多于 NREM）与总学习和回忆能力下降有关。我们发现，REM ODI 与总学习之间的负相关主要由 60 岁以上的成年人驱动。此外，REM-NREM ODI 比值与总学习之间的负相关，以及 REM-NREM RDI 比值与长时延迟回忆之间的负相关主要由 APOE4 携带者驱动。
OSA 严重程度增加，特别是在 REM 睡眠期间，会对言语记忆产生负面影响，尤其是对 AD 风险较高的人群。这些发现强调了即使总体 AHI 较低，积极筛查和治疗 REM OSA 的潜在重要性。
