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呼吸暂停-低通气指数所包含的呼吸暂停事件与阿尔茨海默病的不良结局明显相关。

Breathing cessation events that compose the apnea-hypopnea index are distinctively associated with the adverse outcomes in Alzheimer's disease.

机构信息

Translational Research in Respiratory Medicine (TRRM), Hospital Universitari Arnau de Vilanova-Santa Maria, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain.

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.

出版信息

Alzheimers Res Ther. 2023 Jul 14;15(1):123. doi: 10.1186/s13195-023-01266-x.

Abstract

BACKGROUND

Previous studies challenge the impact of obstructive sleep apnea (OSA) once patients are diagnosed with Alzheimer's disease (AD). Nevertheless, OSA recognizably disrupts sleep, and relevant associations between sleep, AD pathological markers, and cognition have been demonstrated. We aimed to further explore this, evaluating the associations between each breathing cessation event that compose the apnea-hypopnea index (AHI) and the sleep structure to finally investigate whether this was related to increased levels of AD markers and higher cognitive decline.

METHODS

Observational, prospective study, including consecutive patients diagnosed with mild-moderate AD. The participants were submitted to overnight polysomnography followed by a cerebrospinal fluid collection for AD pathological markers levels determination. Neuropsychological assessment was performed at baseline and after 12 months of follow-up.

RESULTS

The cohort was composed of 116 patients (55.2% females) with a median [p25;p75] age of 76.0 [72.0;80.0] years and an AHI of 25.9 [15.1;48.5], which was mainly defined by the presence of hypopneas and obstructive apneas. These were distinctively associated with the sleep structure, with obstructive apneas being related to arousals and sleep lightening and hypopneas being related to an increased number of arousals only. Despite having a lower frequency, mixed and central apneas also presented associations with the sleep structure, particularly increasing the time spent in the lighter sleep stages. In relation to AD pathological markers, obstructive and mixed apneas were related to an augment in neurofilament light levels while hypopneas were associated with a higher phosphorylated-tau/amyloid-beta protein ratio. Hypopneas were the most important event for an increased cognitive decline at the 12-month follow-up.

CONCLUSIONS

Our findings highlight the importance of a patient-centered approach, with a comprehensive and detailed analysis of the AHI to effectively predict the different outcomes and tailor the appropriate therapeutic strategies.

摘要

背景

先前的研究对阻塞性睡眠呼吸暂停(OSA)患者在被诊断为阿尔茨海默病(AD)后的影响提出了挑战。然而,OSA 明显会扰乱睡眠,并且已经证明了睡眠、AD 病理标志物与认知之间存在相关关系。我们旨在进一步探索这一点,评估组成呼吸暂停低通气指数(AHI)的每个呼吸暂停事件与睡眠结构之间的关系,最终研究这是否与 AD 标志物水平升高和认知下降更快有关。

方法

这是一项观察性、前瞻性研究,纳入了连续诊断为轻度至中度 AD 的患者。参与者接受了一夜的多导睡眠图检查,随后采集脑脊液以确定 AD 病理标志物水平。在基线和 12 个月随访时进行了神经心理学评估。

结果

该队列由 116 名患者(55.2%为女性)组成,中位数[25 分位;75 分位]年龄为 76.0[72.0;80.0]岁,呼吸暂停低通气指数(AHI)为 25.9[15.1;48.5],主要由低通气和阻塞性呼吸暂停定义。这些与睡眠结构明显相关,阻塞性呼吸暂停与觉醒和睡眠变浅有关,而低通气仅与觉醒次数增加有关。尽管发生频率较低,但混合性和中枢性呼吸暂停也与睡眠结构有关,尤其是增加了更浅的睡眠阶段的时间。就 AD 病理标志物而言,阻塞性和混合性呼吸暂停与神经丝轻链水平升高有关,而低通气与磷酸化 tau/淀粉样蛋白 beta 蛋白比值升高有关。低通气是在 12 个月随访时认知下降增加的最重要事件。

结论

我们的研究结果强调了以患者为中心的方法的重要性,需要对 AHI 进行全面、详细的分析,以有效预测不同的结果并制定合适的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5966/10347810/4b1bb0faa9eb/13195_2023_1266_Fig1_HTML.jpg

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