Correlation Between OCT-A Biomarkers and Cognitive Impairment in Patient Affected by Chronic Atrial Fibrillation: a Pilot Study

The OCTAF study is a monocentric, cross-sectional pilot investigation conducted at UZ Brussels that aims to explore the association between retinal microvascular characteristics and cognitive impairment in patients with atrial fibrillation. Atrial fibrillation is the most common sustained cardiac arrhythmia and represents a growing public health concern, particularly in aging populations. While its association with stroke and thromboembolic complications is well established, increasing evidence indicates that AF is also independently linked to cognitive decline, even in patients without clinically apparent stroke. The mechanisms underlying this association remain incompletely understood but are thought to involve a combination of silent cerebral infarctions, microbleeds, chronic cerebral hypoperfusion, systemic inflammation, and shared vascular risk factors such as hypertension, diabetes, and atherosclerosis. Cognitive impairment in AF patients is clinically significant because it negatively impacts quality of life, treatment adherence, and long-term outcomes, thereby increasing the burden on healthcare systems.

Despite this, routine screening for cognitive impairment in AF patients is not widely implemented, largely due to the complexity, cost, and limited accessibility of conventional neuroimaging and neuropsychological assessments. This has led to growing interest in identifying alternative, non-invasive biomarkers that can facilitate early detection. The retina provides a unique opportunity in this regard, as it shares embryological origin and microvascular characteristics with the brain. The emerging field of oculomics focuses on the use of retinal imaging to detect systemic and neurological diseases. Optical Coherence Tomography Angiography is a particularly promising modality because it enables high-resolution visualization of retinal microvasculature without the need for contrast agents, allowing quantitative assessment of parameters such as vessel density and the foveal avascular zone.

Previous research investigating retinal biomarkers in neurodegenerative conditions such as Alzheimer's disease and mild cognitive impairment has produced inconsistent findings, with some studies reporting reduced vessel density and enlarged foveal avascular zones, while others found no significant differences. Similarly, studies in atrial fibrillation populations have demonstrated alterations in retinal microvasculature compared to healthy controls, including reduced perfusion and structural retinal changes potentially related to ischemia. However, no prior study has specifically examined retinal OCT-A parameters in AF patients stratified by cognitive status, which represents an important gap in knowledge that this study seeks to address.

The OCTAF study will recruit 40 patients diagnosed with atrial fibrillation from the outpatient cardiology clinic at UZ Brussels. Eligible participants must be aged 40 years or older, have a confirmed diagnosis of AF, possess adequate medical records, and provide informed consent. Patients with a history of stroke or thromboembolic events, significant ocular disease, recent ocular surgery, systemic conditions affecting retinal microvasculature such as diabetes or severe organ failure, neurodegenerative or psychiatric disorders, or poor-quality OCT-A imaging will be excluded in order to minimize confounding factors. The study is designed as a pilot, and therefore the sample size is chosen to allow estimation of variability and feasibility rather than to achieve statistical power for hypothesis testing.

All participants will attend a single study visit at the Ophthalmology Department. During this visit, they will first complete a standardized questionnaire to collect demographic information, including age, sex, height, weight, and educational level, as well as data on cardiovascular risk factors such as hypertension, hyperlipidemia, smoking, alcohol consumption, and medication use, including anticoagulant therapy. Cognitive function will then be assessed using the Montreal Cognitive Assessment, a brief screening tool that evaluates multiple cognitive domains including memory, attention, executive function, language, visuospatial abilities, and orientation. The test takes approximately ten minutes to complete, and a score below 26 is considered indicative of cognitive impairment, with an adjustment of one point for individuals with lower educational attainment. The MoCA test is administered prior to retinal imaging to avoid interference from pupil dilation, which can temporarily impair visual performance and potentially affect test results.