PURPOSE: To evaluate the association between diabetic retinopathy (DR) and cerebral disease or cognitive im-pairment. DESIGN: Systematic review and meta-analysis. METHOD: The hypothesis was formulated prior to data collection. Cross-sectional studies and cohort studies that assessed the association between any measure of DR and cerebral small vessel disease or any type of cognitive im-pairment in diabetic participants were included. The data were independently extracted by two investigators. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines RESULTS: A total of 27 studies were included. The combined odds ratio of 5 cross-sectional/cohort studies that reported that the associations between DR and cere-bral structural changes was 1.75 (95% confidence in-terval [CI]: 1.36-2.25). The combined hazard ratio of 4 cohort studies that examined the association between DR and cognitive impairment events was 1.47 (95% CI: 1.22-1.78). The combined odds ratio of 14 cross-sectional/cohort studies that examined the association between DR and different cognitive impairment events was 1.43 (95% CI: 1.06-1.93). The overall coefficient ( 5) of 4 studies that examined the relationship between DR and specific cognitive performance was 0.09 (95% CI: 0.00-0.18). Considering the quality of the data, we have performed subgroup analysis in studies scored > 7 and studies scored < 7, respectively, according to the Newcastle -Ottawa scale. CONCLUSION: The present meta-analysis suggests that DR is associated with an increased risk of structural ab-normalities in the brain and cognitive impairment. This association remained significant after adjusting for blood glucose, and the presence of hypertension, indicating that DR is an important danger signal for cerebral abnormal-ities. (C) 2022 Elsevier Inc. All rights reserved.