Cognitive Function in Obstructive Sleep Apnea

Официальное название

Cognitive Function and Pathophysiological Mechanisms in Adults With Obstructive Sleep Apnea: Long-term Impact of Positive Airway Pressure Therapy

Обзор

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and has been increasingly recognized as a contributor to cognitive decline and a potential risk factor for neurodegeneration. Previous studies have identified several associated comorbidities, including vascular dysfunction, metabolic alterations, and neuroinflammatory changes. However, the impact and underlying interplay of these pathophysiological mechanisms remain poorly understood due to the lack of integrated, multidimensional assessment. This prospective, observational, longitudinal cohort study aims to investigate cognition and OSA-related physiological and pathophysiological processes in 100 adults newly diagnosed with OSA, who have no history of chronic diseases (except for overweight and obesity) and are not receiving chronic medication. A subgroup of patients with moderate to severe OSA indicated for positive airway pressure (PAP) therapy will be followed to evaluate its long-term effects on cognitive function and related mechanisms. All participants will undergo polysomnography (PSG), comprehensive neuropsychological assessment, brain MRI with volumetric analysis, biomarker profiling from blood and saliva, and evaluation of endothelial function, baroreflex sensitivity, and gut microbiome composition at baseline and after 12 months. PAP adherence will be continuously monitored. The primary objective of this study is to characterize the profile of cognitive impairment associated with OSA. Secondary exploratory analyses will focus on factors contributing to neurocognitive dysfunction in OSA.

Подробное описание

1. Background OSA is a multifaceted sleep disorder characterized by repeated episodes of upper airway obstruction during sleep, leading to significant reductions in airflow and oxygenation. Beyond its primary respiratory manifestations, OSA is associated with major comorbidities such as cardiovascular, metabolic, and neurocognitive disorders, affecting overall health and quality of life. Epidemiological data suggest that OSA affects nearly one billion individuals worldwide, yet remains markedly underdiagnosed, particularly in middle-aged and older adults. Chronic intermittent hypoxia and sleep fragmentation have been implicated in the disruption of neural networks involved in attention, executive function, memory, and emotion regulation. Neuroimaging studies further support these findings, revealing region-specific brain alterations such as hippocampal and cortical atrophy, white-matter hyperintensities, and changes in cerebral perfusion and metabolism. These mechanisms may contribute to accelerated brain aging and increase the vulnerability to neurodegenerative processes. With the global rise in dementia and aging populations, identifying modifiable contributors to cognitive decline is critical. Given that OSA is a treatable condition, timely diagnosis and effective management may represent one of the most accessible interventions to prevent or delay cognitive deterioration in vulnerable populations. 2. Aim of the study The primary aim of this study is to perform a detailed cognitive assessment in patients with OSA. The investigators seek to analyze the baseline prevalence, severity, and pattern of cognitive deficits in this population to gain a clearer understanding of the initial cognitive status from which potential therapeutic or disease-related changes may occur. The secondary aims of this study are exploratory. The investigators plan to investigate potential associations between cognitive impairment and a spectrum of PSG, sleep-related, neuroimaging, anthropometric, laboratory, and vascular measures. The investigators aim to compare the sensitivity of the Montreal Cognitive Assessment (MoCA) with that of a comprehensive neuropsychological battery. Furthermore, the investigators will evaluate the longitudinal effects of PAP therapy on cognition and the related processes under investigation. 3. Inclusion criteria Patients with newly diagnosed OSA who have no history of other chronic diseases except for overweight and obesity, are not taking any medication, and are aged between 18 and 65 years. 4. Study methodology This is a prospective, observational, single-centre cohort study conducted at the Sleep Laboratory of the 1st Department of Neurology, Faculty of Medicine, Comenius University and University Hospital Bratislava. One hundred adults with OSA will be examined at baseline and after 12 months. As part of standard clinical care, all participants will undergo overnight diagnostic PSG to confirm the OSA diagnosis and determine its severity. Patients indicated for PAP therapy will start treatment according to clinical indications, with adherence monitored via device memory cards. Additional research assessments include neuropsychological testing, brain MRI with volumetry, blood and saliva biomarker analysis, assessment of vascular functions, anthropometric measurements, oxidative stress evaluation, and gut microbiome analysis. All assessments will be performed by trained research personnel in a standardized order. Participants will first be hospitalized to undergo PSG to confirm the OSA diagnosis. After confirmation, those meeting the inclusion criteria and providing informed consent will be enrolled in the study. 5. What are the possible benefits and risks of participating? Participants may benefit from early detection of cognitive dysfunction, metabolic or vascular abnormalities, and sleep-related pathology. Risks associated with study participation are minimal and primarily related to standard blood sampling and mild discomfort during assessments. No experimental or invasive interventions are applied.

Первичные конечные точки

• Rey Auditory - Verbal Learning Test (RAVLT) [Срок оценки: Baseline]
• Figure Copy Task [Срок оценки: Baseline]
• Controlled Oral Word Association Test (COWAT) [Срок оценки: Baseline]
• Category Fluency Test [Срок оценки: Baseline]
• Trail Making Test (TMT) [Срок оценки: Baseline]
• The Stroop Color and Word Test [Срок оценки: Baseline]
• Digit Span [Срок оценки: Baseline]
• Montreal Cognitive Assessment (MoCA) [Срок оценки: Baseline]
• Generalized Anxiety Disorder 7-item scale (GAD - 7) [Срок оценки: Baseline]
• Patient´s Health Questionnaire (PHQ - 9) [Срок оценки: Baseline]

Вторичные конечные точки (12)

• Apnea-Hypopnea Index (AHI) [Срок оценки: Baseline]
• Apnea-Hypopnea Index (AHI) 12 months [Срок оценки: 12 months]
• Positive Airway Pressure (PAP) Therapy Adherence [Срок оценки: 12 months]
• Pittsburgh Sleep Quality Index (PSQI) [Срок оценки: Change from baseline to 12 months]
• Epworth Sleepiness Scale (ESS) [Срок оценки: Change from baseline to 12 months]
• Brain Volumetry [Срок оценки: Change from baseline to 12 months]
• Body Mass Index (BMI) [Срок оценки: Change from baseline to 12 months]
• Apolipoprotein E (APOE) [Срок оценки: Baseline]
• Plasma Neurofilament Light Chain (pNfL) [Срок оценки: Change from baseline to 12 months]
• Total cholesterol [Срок оценки: Change from baseline to 12 months]
• Trolox Equivalent Antioxidant Capacity (TEAC) [Срок оценки: Change from baseline to 12 months]
• Reactive Hyperemia Index (RHI) [Срок оценки: Change from baseline to 12 months]

Критерии участия

Критерии включения

• Informed consent.
• Age 18 - 65 years.
• Newly diagnosed OSA according to the criteria of the American Academy of Sleep Medicine Guidelines (overnight PSG with an AHI ≥5 events per hour, hypopneas defined by ≥ 10 seconds of airflow reduction accompanied by ≥ 3% desaturation or an arousal).
• Able to accomplish relevant tests and follow-up.

Критерии исключения

• History of any chronic disease other than overweight and obesity.
• Severe psychiatric condition that could affect cognitive functions.
• Chronic use of medication or nicotine that may affect the study results.
• Prior neuropsychological assessment less than 6 months before the start of the research.
• Prior therapy for OSA (i.e., CPAP, upper airway surgery, or oral appliance).
• Motor or sensory deficits that would significantly complicate test administration.
• Patients who do not have Slovak as their native language actively used in daily communication.
• Considered by the study team as not suitable for enrollment based on clinical judgment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Словакия · 1 центр

• 1st Department of Neurology, Faculty of Medicine, Comenius University and University Hospi — Bratislava

Публикации

• Sehr T, Akgun K, Benkert P, Kuhle J, Ziemssen T, Brandt MD. Effects of obstructive sleep apnea treatment on neurodegenerative biomarker neurofilament light chain and cognitive performance. J Sleep Res. 2024 Oct;33(5):e14164. doi: 10.1111/jsr.14164. Epub 2024 Feb 13. PMID 38351662
• Xue X, Zhao Z, Zhao LB, Gao YH, Xu WH, Cai WM, Chen SH, Li TJ, Nie TY, Rui D, Ma Y, Qian XS, Lin JL, Liu L. Gut microbiota changes in healthy individuals, obstructive sleep apnea patients, and patients treated using continuous positive airway pressure: a whole-genome metagenomic analysis. Sleep Breath. 2024 Nov 26;29(1):11. doi: 10.1007/s11325-024-03185-z. PMID 39589660
• Silva WA, Almeida-Pititto B, Santos RB, Aielo AN, Giatti S, Parise BK, Souza SP, Vivolo SF, Lotufo PA, Bensenor IM, Drager LF. Obstructive sleep apnea is associated with lower adiponectin and higher cholesterol levels independently of traditional factors and other sleep disorders in middle-aged adults: the ELSA-Brasil cohort. Sleep Breath. 2021 Dec;25(4):1935-1944. doi: 10.1007/s11325-021-02290-7. PMID 33590375
• Salari N, Khazaie H, Abolfathi M, Ghasemi H, Shabani S, Rasoulpoor S, Mohammadi M, Rasoulpoor S, Khaledi-Paveh B. The effect of obstructive sleep apnea on the increased risk of cardiovascular disease: a systematic review and meta-analysis. Neurol Sci. 2022 Jan;43(1):219-231. doi: 10.1007/s10072-021-05765-3. Epub 2021 Nov 19. PMID 34797460
• Durtette A, Dargent B, Gierski F, Barbe C, Deslee G, Perotin JM, Henry A, Launois C. Impact of continuous positive airway pressure on cognitive functions in adult patients with obstructive sleep apnea: A systematic review and meta-analysis. Sleep Med. 2024 Nov;123:7-21. doi: 10.1016/j.sleep.2024.08.019. Epub 2024 Aug 22. PMID 39226674
• Bubu OM, Andrade AG, Umasabor-Bubu OQ, Hogan MM, Turner AD, de Leon MJ, Ogedegbe G, Ayappa I, Jean-Louis G G, Jackson ML, Varga AW, Osorio RS. Obstructive sleep apnea, cognition and Alzheimer's disease: A systematic review integrating three decades of multidisciplinary research. Sleep Med Rev. 2020 Apr;50:101250. doi: 10.1016/j.smrv.2019.101250. Epub 2019 Dec 12. PMID 31881487
• Xu H, Liu Y, Li C, Li X, Shen L, Wang H, Liu F, Zou J, Xia Y, Huang W, Liu Y, Gao Z, Fu Y, Wang F, Huang S, Song Z, Song F, Gao Y, Peng Y, Zou J, Zhu H, Liu S, Li L, Zhu X, Xiong Y, Hu Y, Yang J, Li Y, Gao F, Guo Q, Huang H, Zhang W, Li J, Chen Y, Dong P, Yang J, Lv J, Wang P, Sun Y, Qian B, Yaffe K, Guan J, Yi H, Leng Y, Yin S. Effects of Continuous Positive Airway Pressure on Neuroimaging Biomar PMID 39998447

Идентификаторы

NCT: NCT07364318 · CUFM1DN-0111202431122025 · VEGA 1/0075/25

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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