Diabetic Retinopathy Predicts Risk of Alzheimer’s Disease: A Danish Registry-Based Nationwide Cohort Study

Abstract

Background: Retinal neurodegeneration is evident in early diabetic retinopathy (DR) which may be associated with other neurodegenerative diseases like Alzheimer's disease (AD). Objective: To investigate diabetes and DR as a risk marker of present and incident AD. Methods: A register-based cohort study was performed. We included 134,327 persons with diabetes above 60 years of age, who had attended DR screening, and 651,936 age- and gender-matched persons without diabetes. Results: At baseline, the prevalence of AD was 0.7% and 1.3% among patients with and without diabetes, respectively. In a multivariable regression model, patients with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.59–0.68). During follow-up, incident AD was registered for 1473 (0.35%) and 6,899 (0.34%) persons with and without diabetes, respectively. Compared to persons without diabetes, persons with diabetes and no DR had a lower risk to develop AD (adjusted HR 0.87, 95% CI 0.81–0.93), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08–1.43). When persons with diabetes and no DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.18–1.53). Conclusion: Individuals with diabetes without DR were less likely to develop AD compared to persons without diabetes. However, individuals with DR had a 34% higher risk of incident AD, which raise the question whether screening for cognitive impairment should be done among individuals with DR.

Five-Year Incidence of Proliferative Diabetic Retinopathy and Associated Risk Factors in a Nationwide Cohort of 201 945 Danish Patients with Diabetes

“…The distribution of diabetes types in the population was determined by combining diagnostic codes (International Classification of Diseases 10 codes) for diabetes and codes for prescription (Anatomical Therapeutic Chemical Classification System codes) of insulin. Pedersen et al 18 19 We measured progression in both eyes separately. Consequently, some patients contribute with 1 eye and some with 2 eyes.…”

Factors Associated with Lower Risk of Cataract in Type 2 Diabetics: National Health Insurance Claims Data Study

“…Another study by Grauslund et al reported that individuals with diabetes without diabetic retinopathy were less likely to develop Alzheimer's disease compared to persons without diabetes. However, individuals with diabetic retinopathy had a 34% higher risk of incident Alzheimer's disease (Pedersen et al 2022). This might indicate that prevention or treatment of dementia could affect the risk of ocular complications in diabetics.…”

Age-Related Eye Diseases in Individuals With Mild Cognitive Impairment and Alzheimer's Disease

“…Previous studies investigating the association between DR and cognitive function all focused on DR as the independent factor, i.e., as a potential marker for present or incident CIND/AD. To this end, they found that patients with DR had increased prevalence (Ong et al, 2012 ; Liao et al, 2017 ) and incidence (Gupta et al, 2019 ) of CIND, as well as increased incidence of AD (Chen et al, 2016 ; Lee et al, 2019 ; Pedersen et al, 2022 ). A recent systematic review and meta-analysis support these results by concluding that having moderate DR or worse was strongly associated with cognitive impairment (Cheng et al, 2021 ).…”