Association between diabetic retinopathy and neurodegenerative diseases in the All of Us research program

While diabetic retinopathy (DR) has previously been linked to neurodegenerative diseases, it remains unclear whether DR independently reflects neurodegenerative diseases beyond those attributable to diabetes itself. In this study, we leveraged data from the All of Us Research Program to assess whether DR serves as an independent marker of neurodegenerative disease among individuals with diabetes.

A matched case-control, cross-sectional study was conducted using data from the All of Us Research Program (US-based EHR database). Three groups (exactly matched by age, sex, and race) were created and compared: individuals with both DR and DM (DR+DM, n = 7629), individuals with DM but no DR (DM-only, n = 22,887), and individuals without DM (n = 22,887). Outcomes included dementia, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Univariate and multivariate logistic regression analyses were performed, adjusting for demographics, comorbidities and diabetes-related mediators.

In multivariable analysis, DM-only was associated with increased odds of dementia (adjusted odds ratio [aOR] 1.28, 95 % CI: 1.08-1.51; p = 0.004). However, DR in the setting of DM (DM+DR vs. DM-only) was not associated with further increased odds of neurodegenerative disease outcome in multivariate models (aOR for dementia 1.18, 95 % CI: 0.94-1.49). No significant associations were identified for AD, PD, or MS (all p ≥ 0.10).

Diabetic retinopathy was not associated with increased rates of neurodegenerative diseases beyond that conferred by diabetes itself, and the relationship may be mediated by diabetes severity and related comorbidities.