Early Alzheimer's Disease Detection from Retinal OCT Images: A UK Biobank Study

Alterations in retinal layer thickness, measurable using Optical Coherence Tomography (OCT), have been associated with neurodegenerative diseases such as Alzheimer's disease (AD). While previous studies have mainly focused on segmented layer thickness measurements, this study explored the direct classification of OCT B-scan images for the early detection of AD. To our knowledge, this is the first application of deep learning to raw OCT B-scans for AD prediction in the literature. Unlike conventional medical image classification tasks, early detection is more challenging than diagnosis because imaging precedes clinical diagnosis by several years. We fine-tuned and evaluated multiple pretrained models, including ImageNet-based networks and the OCT-specific RETFound transformer, using subject-level cross-validation datasets matched for age, sex, and imaging instances from the UK Biobank cohort. To reduce overfitting in this small, high-dimensional dataset, both standard and OCT-specific augmentation techniques were applied, along with a year-weighted loss function that prioritized cases diagnosed within four years of imaging. ResNet-34 produced the most stable results, achieving an AUC of 0.62 in the 4-year cohort. Although below the threshold for clinical application, our explainability analyses confirmed localized structural differences in the central macular subfield between the AD and control groups. These findings provide a baseline for OCT-based AD prediction, highlight the challenges of detecting subtle retinal biomarkers years before AD diagnosis, and point to the need for larger datasets and multimodal approaches.