Cognitive Function in Obstructive Sleep Apnea (CUFM1DN)

January 15, 2026 updated by: Comenius University

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

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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Branislav Kollar, prof. MD PhD. MPH.
Phone Number: +421 948 334 417
Email: b.kollar.md@gmail.com

Study Contact Backup

Name: Stela Biathova, MA
Phone Number: +421 905 218 668
Email: sbiathova@gmail.com

Study Locations

Slovakia
- - Bratislava, Slovakia, 813 72
    - Recruiting
    - 1st Department of Neurology, Faculty of Medicine, Comenius University and University Hospital Bratislava, Slovakia
    - Contact:
      
      Peter Musil, PhD.
      
      Phone Number: +421903836788
      
      Email: peter.musil@fmed.uniba.sk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rey Auditory - Verbal Learning Test (RAVLT) Time Frame: 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.	Baseline
Figure Copy Task Time Frame: 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.	Baseline
Controlled Oral Word Association Test (COWAT) Time Frame: 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.	Baseline
Category Fluency Test Time Frame: 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.	Baseline
Trail Making Test (TMT) Time Frame: 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.	Baseline
The Stroop Color and Word Test Time Frame: 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.	Baseline
Digit Span Time Frame: 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.	Baseline
Montreal Cognitive Assessment (MoCA) Time Frame: 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.	Baseline
Generalized Anxiety Disorder 7-item scale (GAD - 7) Time Frame: 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.	Baseline
Patient´s Health Questionnaire (PHQ - 9) Time Frame: 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.	Baseline
Rey Auditory - Verbal Learning Test (RAVLT) 12 moths Time Frame: 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.	Change from baseline to 12 months
Figure Copy Task 12 months Time Frame: 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.	Change from baseline to 12 months
Controlled Oral Word Association Test (COWAT) 12 months Time Frame: 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.	Change from baseline to 12 months
Category Fluency Test 12 months Time Frame: 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.	Change from baseline to 12 months
Trail Making Test (TMT) 12 months. Time Frame: 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.	Change from baseline to 12 months
The Stroop Color and Word Test 12 months. Time Frame: 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.	Change from baseline to 12 months
Digit Span 12 months. Time Frame: 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.	Change from baseline to 12 months
Montreal Cognitive Assessment (MoCA) 12 months. Time Frame: 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.	Change from baseline to 12 months
Generalized Anxiety Disorder 7-item scale (GAD - 7) 12 months. Time Frame: 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.	Change from baseline to 12 months
Patient´s Health Questionnaire (PHQ - 9) 12 months. Time Frame: 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.	Change from baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnea-Hypopnea Index (AHI) Time Frame: 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.	Baseline
Apnea-Hypopnea Index (AHI) 12 months Time Frame: 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.	12 months
Positive Airway Pressure (PAP) Therapy Adherence Time Frame: 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.	12 months
Pittsburgh Sleep Quality Index (PSQI) Time Frame: 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.	Change from baseline to 12 months
Epworth Sleepiness Scale (ESS) Time Frame: 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.	Change from baseline to 12 months
Brain Volumetry Time Frame: 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.	Change from baseline to 12 months
Body Mass Index (BMI) Time Frame: Change from baseline to 12 months	BMI calculated as weight (kg) divided by height squared (m²). Units: kg/m². Higher values indicate greater adiposity.	Change from baseline to 12 months
Apolipoprotein E (APOE) Time Frame: 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.	Baseline
Plasma Neurofilament Light Chain (pNfL) Time Frame: Change from baseline to 12 months	A biomarker of neuroaxonal injury. Units: pg/mL. Higher concentrations indicate greater neuronal damage.	Change from baseline to 12 months
Total cholesterol Time Frame: 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.	Change from baseline to 12 months
Trolox Equivalent Antioxidant Capacity (TEAC) Time Frame: 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.	Change from baseline to 12 months
Reactive Hyperemia Index (RHI) Time Frame: 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.	Change from baseline to 12 months
Baroreflex Sensitivity Time Frame: Change from baseline to 12 months	Indicator of autonomic cardiovascular regulation measured via Finometer. Units: ms/mmHg. Higher values indicate better baroreflex control.	Change from baseline to 12 months
Gut Microbiome Composition Time Frame: 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.	Change from baseline to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Comenius University

Collaborators

University Hospital Bratislava

Slovak Academy of Sciences

Investigators

Study Director: Peter Turcani, prof. MD PhD., 1st Department of Neurology, Faculty of Medicine, Comenius University and University Hospital Bratislava, Slovakia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2024

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

November 14, 2025

First Submitted That Met QC Criteria

January 15, 2026

First Posted (Actual)

January 23, 2026

Study Record Updates

Last Update Posted (Actual)