Association between retinal arteriolar branching geometry and risk of Alzheimer’s disease

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease with an increasing fatality rate and population burden. Previously, retinal vascular parameters have been linked to AD, suggesting assessment of retinal vascular parameters may offer a new target for screening patients at risk of AD. Aim To investigate the association between retinal arteriolar branching geometry and risk for Alzheimer’s disease. Design and Setting: Retrospective analysis of cohort study. Methods Participants of the UK Biobank with gradable fundoscopy images and free of AD at baseline were included for analyses. Retina-based Microvascular Health Assessment System (RMHAS) was applied to retinal images to segment arterioles and quantify retinal arteriolar branching parameters (angular asymmetry, AA, and branching coefficient, BC). Cox proportional hazards regression models investigated the associations between retinal arteriolar branching parameters as continuous and categorical variables in quantiles and incident AD. Results We included a total of 29,483 participants. 83(0.28%) participants developed AD during a median of 10.98 years. When modeled as continuous variables, angular asymmetry, and branching coefficient were significantly associated with Alzheimer’s disease (HR = 5.05, 95% CI = 1.82–14.1, P = 0.002; HR = 0.14, 95% CI = 0.02–0.75, P = 0.022, respectively). Such associations were also valid when BC and AA were analyzed as categorical variables (smallest quartile vs biggest three quartiles; HR = 2.97, 95% CI = 1.47–6.02, P = 0.002; HR = 0.43, 95% CI = 0.23–0.83; P = 0.012). Increased retinal arteriolar angular asymmetry and decreased branching coefficient conferred a long-term risk of AD. Conclusions This study found a significant association between retinal arteriolar branching geometry and the risk of AD, suggesting its potential value as a biomarker for AD.