Cognitive Functions, OSA - Obstructive Sleep Apnea
Conditions
Keywords
Cognitive Function, Positive Airway Pressure Therapy, Obstructive Sleep Apnea, Neuroimaging, Biomarkers, Vascular Changes, Metabolic Changes
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Comenius University
University Hospital Bratislava
Slovak Academy of Sciences
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Informed consent. 2. Age 18 - 65 years. 3. 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). 4. Able to accomplish relevant tests and follow-up.
Exclusion criteria
1. History of any chronic disease other than overweight and obesity. 2. Severe psychiatric condition that could affect cognitive functions. 3. Chronic use of medication or nicotine that may affect the study results. 4. Prior neuropsychological assessment less than 6 months before the start of the research. 5. Prior therapy for OSA (i.e., CPAP, upper airway surgery, or oral appliance). 6. Motor or sensory deficits that would significantly complicate test administration. 7. Patients who do not have Slovak as their native language actively used in daily communication. 8. Considered by the study team as not suitable for enrollment based on clinical judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rey Auditory - Verbal Learning Test (RAVLT) | 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 | 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) | 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 | 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) | 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 | 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 | 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) | 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) | 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) | 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 | 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 | 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 | 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 | 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. | 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. | 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. | 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. | 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. | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apnea-Hypopnea Index (AHI) | Baseline | A polysomnographic measure representing the number of apneas and hypopneas per hour of sleep. Units: events per hour. Higher scores indicate more severe OSA. |
| Apnea-Hypopnea Index (AHI) 12 months | 12 months | A polysomnographic measure representing the number of apneas and hypopneas per hour of sleep. Units: events per hour. Higher scores indicate more severe OSA. Assessments will be performed after 12 months. |
| Positive Airway Pressure (PAP) Therapy Adherence | 12 months | Objective measure of treatment compliance obtained from PAP device data. Units: average hours of use per night. Higher scores indicate better adherence to therapy. Assessments will be performed after 12 months. |
| Pittsburgh Sleep Quality Index (PSQI) | Change from baseline to 12 months | A self-rated questionnaire comprising 19 items that evaluate sleep quality and disturbances over a one-month interval. Units: global PSQI score (0-21 points); cut-off ≥ 5. Higher scores indicate poorer overall sleep quality. |
| Epworth Sleepiness Scale (ESS) | Change from baseline to 12 months | An 8-item self-report questionnaire measuring habitual daytime sleepiness in common situations. Units: total score (0-24 points); cut-off ≥ 10. Higher scores indicate greater daytime sleepiness. |
| Brain Volumetry | Change from baseline to 12 months | Quantitative assessment of total and regional brain volumes will include total brain volume, gray and white matter volumes, hippocampal volume, cortical thickness, and other regional volumetric measures. Units: mL; changes in volumes reflect structural brain alterations. |
| Body Mass Index (BMI) | Change from baseline to 12 months | BMI calculated as weight (kg) divided by height squared (m²). Units: kg/m². Higher values indicate greater adiposity. |
| Apolipoprotein E (APOE) | Baseline | Genotype Genetic biomarker associated with neurodegenerative risk. Units: genotype category (ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4). ε4 allele presence indicates higher vulnerability to cognitive decline. |
| Plasma Neurofilament Light Chain (pNfL) | Change from baseline to 12 months | A biomarker of neuroaxonal injury. Units: pg/mL. Higher concentrations indicate greater neuronal damage. |
| Total cholesterol | Change from baseline to 12 months | Measure of circulating total cholesterol, representing the combined cholesterol content within all lipoprotein classes. Units: mmol/L. Higher values reflect a more adverse lipid profile. |
| Trolox Equivalent Antioxidant Capacity (TEAC) | Change from baseline to 12 months | Measure of total antioxidant capacity in plasma and saliva. Units: mmol Trolox equivalents/L. Lower TEAC values indicate reduced antioxidant defense and increased susceptibility to oxidative stress. |
| Reactive Hyperemia Index (RHI) | Change from baseline to 12 months | Measure of endothelial function assessed by pulse amplitude tonometry. RHI reflects the vasodilatory response of peripheral arteries following temporary occlusion. Units: ratio. Lower values indicate worse endothelial function. |
| Baroreflex Sensitivity | Change from baseline to 12 months | Indicator of autonomic cardiovascular regulation measured via Finometer. Units: ms/mmHg. Higher values indicate better baroreflex control. |
| Gut Microbiome Composition | Change from baseline to 12 months | Analysis of microbial diversity and abundance from stool samples. Units: Shannon index and Bray-Curtis dissimilarity. Lower alpha diversity and altered beta diversity indicate dysbiosis. |
Countries
Slovakia
Contacts
CONTACTBranislav Kollar, prof. MD PhD. MPH.
CONTACTStela Biathova, MA
STUDY_DIRECTORPeter Turcani, prof. MD PhD.
1st Department of Neurology, Faculty of Medicine, Comenius University and University Hospital Bratislava, Slovakia
Outcome results
None listed