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


Journal

The Lancet. Digital health
ISSN: 2589-7500
Titre abrégé: Lancet Digit Health
Pays: England
ID NLM: 101751302

Informations de publication

Date de publication:
11 2022
Historique:
received: 04 05 2022
revised: 12 08 2022
accepted: 19 08 2022
pubmed: 4 10 2022
medline: 2 11 2022
entrez: 3 10 2022
Statut: ppublish

Résumé

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. 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). 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%]). 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. BrightFocus Foundation.

Sections du résumé

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.

Identifiants

pubmed: 36192349
pii: S2589-7500(22)00169-8
doi: 10.1016/S2589-7500(22)00169-8
pii:
doi:

Substances chimiques

Amyloid beta-Peptides 0

Types de publication

Multicenter Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e806-e815

Subventions

Organisme : Medical Research Council
ID : MR/K003364/1
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests CYC, ARR, SW, CCT, P-AH, and VCTM are filing a patent for the deep learning model in this study. All authors declare no competing interests.

Auteurs

Carol Y Cheung (CY)

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: carolcheung@cuhk.edu.hk.

An Ran Ran (AR)

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Shujun Wang (S)

Department of Computer Science and Engineering, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Victor T T Chan (VTT)

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.

Kaiser Sham (K)

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Saima Hilal (S)

Memory Aging &Cognition Centre, National University Health System, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

Narayanaswamy Venketasubramanian (N)

Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.

Ching-Yu Cheng (CY)

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-National University of Singapore Medical School, Singapore.

Charumathi Sabanayagam (C)

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-National University of Singapore Medical School, Singapore.

Yih Chung Tham (YC)

Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-National University of Singapore Medical School, Singapore.

Leopold Schmetterer (L)

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Singapore Eye Research Institute, Advanced Ocular Engineering and School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.

Gareth J McKay (GJ)

Centre for Public Health, Royal Victoria Hospital, Queen's University Belfast, Belfast, UK.

Michael A Williams (MA)

Centre for Medical Education, Queen's University Belfast, Belfast, UK.

Adrian Wong (A)

Gerald Choa Neuroscience Institute, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Lui Che Woo Institute of Innovative Medicine, Division of Neurology, Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Lisa W C Au (LWC)

Gerald Choa Neuroscience Institute, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Lui Che Woo Institute of Innovative Medicine, Division of Neurology, Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Zhihui Lu (Z)

Jockey Club Centre for Osteoporosis Care and Control, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Medicine and Therapeutics, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Jason C Yam (JC)

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Clement C Tham (CC)

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

John J Chen (JJ)

Department of Ophthalmology and Department of Neurology, Mayo Clinic, Rochester, MN, USA.

Oana M Dumitrascu (OM)

Department of Neurology and Department of Ophthalmology, Division of Cerebrovascular Diseases, Mayo Clinic College of Medicine and Science, Scottsdale, AZ, USA.

Pheng-Ann Heng (PA)

Department of Computer Science and Engineering, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Timothy C Y Kwok (TCY)

Jockey Club Centre for Osteoporosis Care and Control, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Medicine and Therapeutics, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Vincent C T Mok (VCT)

Gerald Choa Neuroscience Institute, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Lui Che Woo Institute of Innovative Medicine, Division of Neurology, Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Dan Milea (D)

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-National University of Singapore Medical School, Singapore.

Christopher Li-Hsian Chen (CL)

Memory Aging &Cognition Centre, National University Health System, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Tien Yin Wong (TY)

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-National University of Singapore Medical School, Singapore; Tsinghua Medicine, Tsinghua University, Beijing, China.

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