Cognitive Function and Pathophysiological Mechanisms in Adults With Obstructive Sleep Apnea: Long-term Impact of Positive Airway Pressure Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Rey Auditory - Verbal Learning Test (RAVLT)
研究概览
简要总结
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.
详细描述
- 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.
- 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.
- 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.
- 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.
- 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Newly diagnosed OSA
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).
结局指标
主要结局
Rey Auditory - Verbal Learning Test (RAVLT)
时间窗: Baseline
Measure of verbal episodic memory, encompassing immediate recall, learning across trials, delayed recall, and recognition. Units: total number of correctly recalled words (0-75); z-score. Higher scores indicate better performance.
Figure Copy Task
时间窗: Baseline
A visuoconstructional task used to assess visual perception, spatial planning, and visual memory. Units: score 0-24 points; z-score. Higher scores indicate better performance.
Controlled Oral Word Association Test (COWAT)
时间窗: Baseline
A verbal fluency task requiring rapid generation of words beginning with specified letters. It assesses phonemic fluency, executive function, and lexical retrieval. Units: number of correct words generated per minute; z-score. Higher scores indicate better performance.
Category Fluency Test
时间窗: Baseline
A semantic fluency measure where subjects list as many words from a given category. It evaluates semantic memory and executive retrieval processes. Units: number of correct words generated per minute; z-score. Higher scores indicate better performance.
Trail Making Test (TMT)
时间窗: Baseline
A two-part test evaluating processing speed, visual search, attention, and task-switching. Units: completion time in seconds; z-score. Shorter completion times indicate better performance.
The Stroop Color and Word Test
时间窗: Baseline
Measure of selective attention, processing speed, cognitive flexibility, and inhibitory control. Units: completion time in seconds; z-score. Shorter completion times indicate better performance.
Digit Span
时间窗: Baseline
A working memory test comprising forward and backward recall of digit sequences. Assesses attention, concentration, and short-term memory. Units: total score (0-14 points); z-score. Higher scores indicate better performance.
Montreal Cognitive Assessment (MoCA)
时间窗: Baseline
General cognition screening targeting attention, executive function, memory, language, visuospatial abilities, and orientation. Units: total score (0-30 points); ≥26 = normal cognition. Higher scores indicate better performance.
Generalized Anxiety Disorder 7-item scale (GAD - 7)
时间窗: Baseline
A 7-item self-report questionnaire to screen and assess the severity of generalized anxiety disorder. Items are rated on a 4-point scale. Units: total score (0-21 points); cut-off ≥ 10. Higher scores indicate greater anxiety symptom severity.
Patient´s Health Questionnaire (PHQ - 9)
时间窗: Baseline
A 9-item scale assessing depression severity based on DSM IV criteria. Items are rated on a 4-point scale. Units: total score (0-27 points); cut-off ≥ 10. Higher scores indicate greater depressive symptom severity.
Rey Auditory - Verbal Learning Test (RAVLT) 12 moths
时间窗: Change from baseline to 12 months
Measure of verbal episodic memory, encompassing immediate recall, learning across trials, delayed recall, and recognition. Units: total number of correctly recalled words (0-75); z-score. Higher scores indicate better performance. Assessments will be performed after 12 months.
Figure Copy Task 12 months
时间窗: Change from baseline to 12 months
A visuoconstructional task used to assess visual perception, spatial planning, and visual memory. Units: score 0-24 points; z-score. Higher scores indicate better performance. Assessments will be performed after 12 months.
Controlled Oral Word Association Test (COWAT) 12 months
时间窗: Change from baseline to 12 months
A verbal fluency task requiring rapid generation of words beginning with specified letters. It assesses phonemic fluency, executive function, and lexical retrieval. Units: number of correct words generated per minute; z-score. Higher scores indicate better performance. Assessments will be performed after 12 months.
Category Fluency Test 12 months
时间窗: Change from baseline to 12 months
A semantic fluency measure where subjects list as many words from a given category. It evaluates semantic memory and executive retrieval processes. Units: number of correct words generated per minute; z-score. Higher scores indicate better performance. Assessments will be performed after 12 months.
Trail Making Test (TMT) 12 months.
时间窗: Change from baseline to 12 months
A two-part test evaluating processing speed, visual search, attention, and task-switching. Units: completion time in seconds; z-score. Shorter completion times indicate better performance. Assessments will be performed after 12 months.
The Stroop Color and Word Test 12 months.
时间窗: Change from baseline to 12 months
Measure of selective attention, processing speed, cognitive flexibility, and inhibitory control. Units: completion time in seconds; z-score. Shorter completion times indicate better performance. Assessments will be performed after 12 months.
Digit Span 12 months.
时间窗: Change from baseline to 12 months
A working memory test comprising forward and backward recall of digit sequences. Assesses attention, concentration, and short-term memory. Units: total score (0-14 points); z-score. Higher scores indicate better performance. Assessments will be performed after 12 months.
Montreal Cognitive Assessment (MoCA) 12 months.
时间窗: Change from baseline to 12 months
General cognition screening targeting attention, executive function, memory, language, visuospatial abilities, and orientation. Units: total score (0-30 points); ≥26 = normal cognition. Higher scores indicate better performance. Assessments will be performed after 12 months.
Generalized Anxiety Disorder 7-item scale (GAD - 7) 12 months.
时间窗: Change from baseline to 12 months
A 7-item self-report questionnaire to screen and assess the severity of generalized anxiety disorder. Items are rated on a 4-point scale. Units: total score (0-21 points); cut-off ≥ 10. Higher scores indicate greater anxiety symptom severity. Assessments will be performed after 12 months.
Patient´s Health Questionnaire (PHQ - 9) 12 months.
时间窗: Change from baseline to 12 months
A 9-item scale assessing depression severity based on DSM IV criteria. Items are rated on a 4-point scale. Units: total score (0-27 points); cut-off ≥ 10. Higher scores indicate greater depressive symptom severity. Assessments will be performed after 12 months.
次要结局
- Apnea-Hypopnea Index (AHI)(Baseline)
- Apnea-Hypopnea Index (AHI) 12 months(12 months)
- Positive Airway Pressure (PAP) Therapy Adherence(12 months)
- Pittsburgh Sleep Quality Index (PSQI)(Change from baseline to 12 months)
- Epworth Sleepiness Scale (ESS)(Change from baseline to 12 months)
- Brain Volumetry(Change from baseline to 12 months)
- Body Mass Index (BMI)(Change from baseline to 12 months)
- Apolipoprotein E (APOE)(Baseline)
- Plasma Neurofilament Light Chain (pNfL)(Change from baseline to 12 months)
- Total cholesterol(Change from baseline to 12 months)
- Trolox Equivalent Antioxidant Capacity (TEAC)(Change from baseline to 12 months)
- Reactive Hyperemia Index (RHI)(Change from baseline to 12 months)
- Baroreflex Sensitivity(Change from baseline to 12 months)
- Gut Microbiome Composition(Change from baseline to 12 months)