Prediction of Alzheimer's Disease Risk Factors from Retinal Images via Deep Learning: Development and Validation of Biologically Relevant Morphological Associations in the UK Biobank
For researchers studying preclinical Alzheimer's disease, this work provides evidence that retinal imaging may capture risk-related structural changes, though the predictive performance is modest and the approach is not yet clinically diagnostic.
The study used deep learning on retinal images from the UK Biobank to predict 12 Alzheimer's disease risk factors, achieving AUROC up to 0.9480 and R² up to 0.7620, and found that saliency-based scores differed between future AD cases and controls, suggesting retinal signatures of AD vulnerability.
The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using UK Biobank CFPs, DL models were trained using 62,876 images from 44,501 unique participants to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.