Color Fundus Photography and Deep Learning Applications in Alzheimer Disease

Objective

To report the development and performance of 2 distinct deep learning models trained exclusively on retinal color fundus photographs to classify Alzheimer disease (AD).

Patients and Methods

Two independent datasets (UK Biobank and our tertiary academic institution) of good-quality retinal photographs derived from patients with AD and controls were used to build 2 deep learning models, between April 1, 2021, and January 30, 2024. ADVAS is a U-Net–based architecture that uses retinal vessel segmentation. ADRET is a bidirectional encoder representations from transformers style self-supervised learning convolutional neural network pretrained on a large data set of retinal color photographs from UK Biobank. The models’ performance to distinguish AD from non-AD was determined using mean accuracy, sensitivity, specificity, and receiving operating curves. The generated attention heatmaps were analyzed for distinctive features.

Results

The self-supervised ADRET model had superior accuracy when compared with ADVAS, in both UK Biobank (98.27% vs 77.20%; P<.001) and our institutional testing data sets (98.90% vs 94.17%; P=.04). No major differences were noted between the original and binary vessel segmentation and between both eyes vs single-eye models. Attention heatmaps obtained from patients with AD highlighted regions surrounding small vascular branches as areas of highest relevance to the model decision making.

Conclusion

A bidirectional encoder representations from transformers style self-supervised convolutional neural network pretrained on a large data set of retinal color photographs alone can screen symptomatic AD with high accuracy, better than U-Net–pretrained models. To be translated in clinical practice, this methodology requires further validation in larger and diverse populations and integrated techniques to harmonize fundus photographs and attenuate the imaging-associated noise.