A deep learning model for detection of Alzheimer's disease based on retinal photographs: a retrospective, multicentre case-control study

Background: There is no simple model to screen for Alzheimer's disease, partly because the diagnosis of Alzheimer's disease itself is complex—typically involving expensive and sometimes invasive tests not commonly available outside highly specialised clinical settings. We aimed to develop a deep learning algorithm that could use retinal photographs alone, which is the most common method of non-invasive imaging the retina to detect Alzheimer's disease-dementia. Methods: In this retrospective, multicentre case-control study, we trained, validated, and tested a deep learning algorithm to detect Alzheimer's disease-dementia from retinal photographs using retrospectively collected data from 11 studies that recruited patients with Alzheimer's disease-dementia and people without disease from different countries. Our main aim was to develop a bilateral model to detect Alzheimer's disease-dementia from retinal photographs alone. We designed and internally validated the bilateral deep learning model using retinal photographs from six studies. We used the EfficientNet-b2 network as the backbone of the model to extract features from the images. Integrated features from four retinal photographs (optic nerve head-centred and macula-centred fields from both eyes) for each individual were used to develop supervised deep learning models and equip the network with unsupervised domain adaptation technique, to address dataset discrepancy between the different studies. We tested the trained model using five other studies, three of which used PET as a biomarker of significant amyloid β burden (testing the deep learning model between amyloid β positive vs amyloid β negative). Findings: 12 949 retinal photographs from 648 patients with Alzheimer's disease and 3240 people without the disease were used to train, validate, and test the deep learning model. In the internal validation dataset, the deep learning model had 83·6% (SD 2·5) accuracy, 93·2% (SD 2·2) sensitivity, 82·0% (SD 3·1) specificity, and an area under the receiver operating characteristic curve (AUROC) of 0·93 (0·01) for detecting Alzheimer's disease-dementia. In the testing datasets, the bilateral deep learning model had accuracies ranging from 79·6% (SD 15·5) to 92·1% (11·4) and AUROCs ranging from 0·73 (SD 0·24) to 0·91 (0·10). In the datasets with data on PET, the model was able to differentiate between participants who were amyloid β positive and those who were amyloid β negative: accuracies ranged from 80·6 (SD 13·4%) to 89·3 (13·7%) and AUROC ranged from 0·68 (SD 0·24) to 0·86 (0·16). In subgroup analyses, the discriminative performance of the model was improved in patients with eye disease (accuracy 89·6% [SD 12·5%]) versus those without eye disease (71·7% [11·6%]) and patients with diabetes (81·9% [SD 20·3%]) versus those without the disease (72·4% [11·7%]). Interpretation: A retinal photograph-based deep learning algorithm can detect Alzheimer's disease with good accuracy, showing its potential for screening Alzheimer's disease in a community setting. Funding: BrightFocus Foundation.