持续正压通气治疗对中-重度阻塞性睡眠呼吸暂停低通气综合征患者嗅觉及认知功能的影响

Effects of continuous positive airway pressure on olfactory and cognitive functions in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome

摘要

目的 系统评估持续正压通气(continuous positive airway pressure, CPAP)治疗对中-重度阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome, OSAHS)患者嗅觉及认知功能的纵向改善作用。方法 纳入90例中-重度OSAHS患者，接受为期6个月的标准化CPAP治疗。分别在基线、治疗3个月和6个月时，采用Sniffin' Sticks嗅觉测试评估嗅觉阈值、辨别力、识别力及总分(threshold-discrimination-identification, TDI)，采用蒙特利尔认知评估量表(Montreal Cognitive Assessment, MoCA)评估认知功能。采用Pearson相关分析评估基线睡眠呼吸暂停低通气指数(apnea-hypopnea index, AHI)与嗅觉、认知功能改善程度(Δ)的相关性，以及嗅觉功能改善与认知功能改善的相关性。结果 疗后，患者嗅觉总分从(19.81±2.88)分提高至(26.49±2.56)分(P<0.05)，MoCA总分从(19.52±2.48)分提高至(22.58±1.87)分(P<0.05)。嗅觉各维度呈现差异化恢复轨迹:阈值和识别力在治疗3个月时即改善(P<0.05)，辨别力至治疗6个月时方显改善(P<0.05)；认知功能中视空间与执行功能、注意力、记忆力在治疗3个月时改善(P<0.05)。嗅觉阈值改善与基线AHI呈正相关(r=0.41, P<0.05)，嗅觉总分改善与认知总分改善亦呈正相关(r=0.46, P<0.05)。亚组分析显示，非肥胖、年龄≤50岁及女性患者的嗅觉改善更为明显(P<0.05)。结论 CPAP治疗可有效改善中-重度OSAHS患者的嗅觉与认知功能，功能恢复呈现时程差异与人群异质性，嗅觉与认知改善存在正相关关系。

Abstract

Objective To longitudinally evaluate the effects of continuous positive airway pressure (CPAP) on olfactory and cognitive functions in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods Ninety patients with moderate-to-severe OSAHS received standardized CPAP therapy for 6 months. Olfactory function, including threshold, discrimination, identification, and the total threshold-discrimination-identification (TDI) score, was assessed using the Sniffin' Sticks test at baseline, 3 months, and 6 months. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA) at the same time points. Pearson correlation analysis was used to assess the relationships between baseline apnea-hypopnea index (AHI) and improvements (Δ) in olfactory and cognitive functions, as well as the correlation between olfactory and cognitive improvements. Results After treatment, the total olfactory score increased from 19.81±2.88 to 26.49±2.56 (P<0.05), and the total MoCA score increased from 19.52±2.48 to 22.58±1.87 (P<0.05). Olfactory subdomains showed differential recovery trajectories: threshold and identification improved significantly at 3 months (P<0.05), while discrimination improved only at 6 months (P<0.05). Among cognitive subdomains, visuospatial/executive function, attention, and memory showed significant improvement at 3 months (P<0.05). Improvement in olfactory threshold was positively correlated with baseline AHI (r=0.41, P<0.05), and improvement in total olfactory score was positively correlated with improvement in total cognitive score (r=0.46, P<0.05). Subgroup analysis revealed that non-obese patients, those aged ≤50 years, and females exhibited greater olfactory improvement (P<0.05). Conclusion CPAP therapy effectively improves olfactory and cognitive functions in patients with moderate to severe OSAHS, with functional recovery demonstrating temporal differences and population heterogeneity. Olfactory improvement is positively correlated with cognitive improvement.

关键词

睡眠呼吸暂停 / 阻塞性 / 嗅觉功能 / 认知功能 / 持续气道正压通气

Key words

Sleep apnea / Obstructive / Olfactory function / Cognitive function / Continuous positive airway pressure

参考文献

[1] Yuan FJ , Zhang SS , Liu X , et al. Correlation between obstructive sleep apnea hypopnea syndrome and hypertension: a systematic review and meta-analysis[J]. Ann Palliat Med, 2021, 10(12): 12251-12261. doi: 10.21037/apm-21-3302

[2] Lyons MM , Bhatt NY , Pack AI , et al. Global burden of sleep-disordered breathing and its implications[J]. Respirology, 2020, 25(7): 690-702. doi: 10.1111/resp.13838

[3] Tondo P , Fanfulla F , Sabato R , et al. Obstructive sleep apnoea-hypopnoea syndrome: state of the art[J]. Minerva Med, 2023, 114(1): 74-89. doi: 10.23736/s0026-4806.22.08190-3

[4] Jonsson Fagerlund M , Franklin KA . Perioperative continuous positive airway pressure therapy: a review with the emphasis on randomized controlled trials and obstructive sleep apnea[J]. Anesth Analg, 2021, 132(5): 1306-1313. doi: 10.1213/ane.0000000000005480

[5] Shieu MM , Zahed AB , Shannon C , et al. Positive airway pressure and cognitive disorders in adults with obstructive sleep apnea: a systematic review of the literature[J]. Neurology, 2022, 99(4): e334-e346. doi: 10.1212/wnl.0000000000200383

[6] Binar M , Gokgoz MC . Olfactory function in patients with obstructive sleep apnea and the effect of positive airway pressure treatment: a systematic review and meta-analysis[J]. Sleep Breath, 2021, 25(4): 1791-1802. doi: 10.1007/s11325-021-02349-5

[7] Berry RB , Brooks R , Gamaldo CE , et al. The AASM manual for the scoring of sleep and associated events[J]. Rules, Terminology and Technical Specifications, Darien, Illinois, American Academy of Sleep Medicine, 2012, 176(2012): 1-7

[8] 中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组, 中华医学会耳鼻咽喉头颈外科学分会鼻科学组, 魏永祥 . 嗅觉障碍诊断和治疗专家共识(2017年)[J]. 中华耳鼻咽喉头颈外科杂志, 2018, 53(7): 484-494. doi: 10.3760/cma.j.issn.1673-0860.2018.07.002

[9] 中华医学会神经病学分会痴呆与认知障碍学组写作组, 中国阿尔茨海默病协会(ADC) . 中国痴呆与认知障碍诊治指南:轻度认知障碍的诊断和治疗[J]. 中华医学杂志, 2010, 90(41): 2887-2893. doi: 10.3760/cma.j.issn.0376-2491.2010.41.003

[10] Magliulo G , De Vincentiis M , Iannella G , et al. Olfactory evaluation in obstructive sleep apnoea patients[J]. Acta Otorhinolaryngol Ital, 2018, 38(4): 338-345. doi: 10.14639/0392-100x-1981

[11] Boerner B , Tini GM , Fachinge r P , et al. Significant improvement of olfactory performance in sleep apnea patients after three months of nasal CPAP therapy-Observational study and randomized trial[J]. PLoS One, 2017, 12(2): e0171087. doi: 10.1371/journal.pone.0171087

[12] Gelardi M , Carbonara G , Maffezzoni E , et al. Regular CPAP utilization reduces nasal inflammation assessed by nasal cytology in obstructive sleep apnea syndrome[J]. Sleep Med, 2012, 13(7): 859-863. doi: 10.1016/j.sleep.2012.04.004

[13] Osorio RS , Gumb T , Pirraglia E , et al. Sleep-disordered breathing advances cognitive decline in the elderly[J]. Neurology, 2015, 84(19): 1964-1971. doi: 10.1212/wnl.0000000000001566

[14] 万晓勇, 赵文瑞, 吴欣然, 等 . 阻塞性睡眠呼吸暂停的脑影像研究: 来自静息态脑电和功能磁共振的证据[J]. 生理学报, 2019, 71(5): 760-768. doi: 10.13294/j.aps.2019.0049

[15] WAN Xiaoyong , ZHAO Wenrui , WU Xinran , et al. The brain imaging studies of obstructive sleep apnea: evidence from resting-state EEG and fMRI[J]. Acta Physiologica Sinica, 2019, 71(5): 760-768. doi: 10.13294/j.aps.2019.0049

[16] Daurat A , Foret J , Bret-Dibat JL , et al. Spatial and temporal memories are affected by sleep fragmentation in obstructive sleep apnea syndrome[J]. J Clin Exp Neuropsychol, 2008, 30(1): 91-101. doi: 10.1080/13803390701236116

[17] Dintica CS , Marseglia A , Rizzuto D , et al. Impaired olfaction is associated with cognitive decline and neurodegeneration in the brain[J]. Neurology, 2019, 92(7): e700-e709. doi: 10.1212/wnl.0000000000006919

[18] Altundag A , Salihoglu M , Tekeli H , et al. Lateralized differences in olfactory function and olfactory bulb volume relate to nasal septum deviation[J]. J Craniofac Surg, 2014, 25(2): 359-362. doi: 10.1097/scs.0000000000000617

[19] Salihoğlu M , Kendirli MT , Altundağ A , et al. The effect of obstructive sleep apnea on olfactory functions[J]. Laryngoscope, 2014, 124(9): 2190-2194. doi: 10.1002/lary.24565

[20] Loch D , Heidel C , Breer H , et al. Adiponectin enhances the responsiveness of the olfactory system[J]. PLoS One, 2013, 8(10): e75716. doi: 10.1371/journal.pone.0075716

[21] Franco R , Garrigós C , Capó T , et al. Olfactory receptors in neural regeneration in the central nervous system[J]. Neural Regen Res, 2025, 20(9): 2480-2494. doi: 10.4103/nrr.nrr-d-24-00495

[22] Xie YQ , Wang SL , Cha XD , et al. Aging and chronic inflammation: impacts on olfactory dysfunction-a comprehensive review[J]. Cell Mol Life Sci, 2025, 82(1): 199. doi: 10.1007/s00018-025-05637-5

[23] Abaffy T , Lu HY , Matsunami H . Sex steroid hormone synthesis, metabolism, and the effects on the mammalian olfactory system[J]. Cell Tissue Res, 2023, 391(1): 19-42. doi: 10.1007/s00441-022-03707