Diabetic retinopathy independently predicts five-year risk of Alzheimer’s disease

Purpose: Diabetes is a risk factor of Alzheimer’s disease (AD), however data on the association between diabetic retinopathy (DR) and AD is limited. Both DR and AD may be viewed as progressive neurovascular disorders and we therefore hypothesized that DR predicts risk of AD. The present study investigates DR as a risk marker of 5-year incident AD.
Methods: We performed a register-based national cohort study, including 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. We investigated the association between DR and AD, both cross-sectionally and prospectively with data collected between 2013 and 2018. AD was defined according to the International Classification of Diseases codes G30* or F00*, as given by the Danish National Patient Registry. To evaluate the risk of present and incident AD among persons with DR, a multivariable logistic regression model and a Cox proportional hazard model were used, adjusting for age, gender, civil status, use of antihypertensive and lipid lowering medication, depression and an adjusted Charlson comorbidity index.
Results: At baseline, the prevalence of AD was 0.7% and 1.3% among persons with and without diabetes respectively. In a multivariable regression model, persons with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.58-0.67). During follow up, incident AD was registered in 1,454 (0.40%) and 6,796 (0.39%) 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 0.88, 95% CI 0.82-0.94), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08-1.43). Still, when persons with diabetes without DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.17-1.52).
Conclusions: In the present nationwide cohort study 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 compared to persons with diabetes without DR. Identification of risk or early detection of AD may provide the opportunity to treat modifiable risk factors to slow or prevent disease progression, or provide adequate help at an earlier stage.