Brain and Cognition Signature Fingerprinting Vascular Health in Diabetic Individuals: An International Multi-Cohort Study

•What is the primary question addressed by this study?Is cognitive signature related to diabetic complications and mortality?•What is the main finding of this study?Cognitive signatures from magnetic resonance imaging and tests are significantly associated with increased risks of mortality and vascular complications in both middle- and older-aged people with diabetes.A faster decline in retinal microcirculation was found in diabetic patients with poorer cognitive function, reflecting the corresponding worse systemic circulation.•What is the meaning of the finding?Questionnaire or brain-imaging-based cognition serves as a potential indicator of mortality and systemic vascular complications in the diabetic population. To evaluate the correlation between cognitive signatures and the risk of diabetic vascular complications and mortality, based on a multicountry prospective study. The participants comprised 27,773 diabetics from the UK Biobank (UKB) and 1307 diabetics from the Guangzhou Diabetic Eye Study (GDES) cohort. The exposures were brain volume and cognitive screening tests for UKB participants, whilst the global cognitive score (GCS) measuring orientation to time and attention, episodic memory, and visuospatial abilities were determined for GDES participants. The outcomes for the UKB group were mortality, as well as macrovascular (myocardial infarction [MI] and stroke), microvascular (end-stage renal disease [ESRD], and diabetic retinopathy [DR]) events. The outcomes for the GDES group were retinal and renal microvascular damage. In the UKB group, a 1-SD reduction in brain gray matter volume was associated with 34%–77% higher risks of incident MI, ESRD, and DR. The presence of impaired memory was associated with 18%–73% higher risk of mortality and ESRD; impaired reaction was associated with 1.2–1.7-fold higher risks of mortality, stroke, ESRD, and DR. In the GDES group, the lowest GCS tertile exhibited 1.4–2.2-fold higher risk of developing referable DR and a twofold faster decline in renal function and retinal capillary density compared with the highest tertile. Restricting data analysis to individuals aged less than 65 years produced consistent results. Cognitive decline significantly elevates the risk of diabetic vascular complications and is correlated with retinal and renal microcirculation damage. Cognitive screening tests are strongly recommended as routine tools for management of diabetes.