Retinal OCTA Phenotyping with LLM Reporting for Alzheimer's Disease

Abstract

Early identification of Alzheimer's disease (AD) remains challenging because established assessment methods can be costly, resource-intensive, or unsuitable for population-scale screening. Optical coherence tomography angiography (OCTA) provides non-invasive visualization of retinal microvasculature, but existing approaches often require diagnostic labels and provide limited measurement-level interpretation. We present an explainable OCTA pipeline that integrates annotation-aware vessel segmentation, layer-specific vascular biomarker extraction, label-free phenotyping, and measurement-grounded LLM reporting. Using 117 ROSE-1 images from 39 subjects, we apply annotation-matched segmentation models to superficial vascular complex (SVC), deep vascular complex (DVC), and combined SVC+DVC representations. The models achieve ROC-AUC values of 0.916-0.970 and Dice scores of 0.695-0.781. Six density and fractal-dimension biomarkers form subject-level profiles for exploratory clustering. Analysis of nine held-out subjects identifies an internally consistent lower-density, lower-fractal-dimension phenotype, although the absence of diagnostic labels prevents clinical interpretation. Reports generated using GPT, Gemini, and Llama are evaluated for measurement grounding, citation faithfulness, and diagnostic caution. Overall, the framework provides a transparent, non-diagnostic connection between retinal vascular measurements, exploratory phenotyping, and evidence-linked interpretation for Alzheimer's research.