Retinal microvascular biomarkers predicting cognitive impairment: insights from the Semmelweis Study

Abstract Background Cognitive decline, particularly vascular cognitive impairment (VCI), poses a growing public health challenge in Hungary's aging population, significantly impacting individual quality of life. The Semmelweis Study, a longitudinal workplace cohort, explores factors contributing to unhealthy brain aging. Dual-task (DT) gait performance-a proxy for cognitive function-reflects the brain's ability to manage simultaneous motor and cognitive tasks. Impaired DT performance indicates cortical inefficiency, when additional cognitive demands compromise gait coordination. This study assessed whether microvascular changes in the central nervous system measured in retinal vessels correlate with DT gait impairments, providing insight into the microvascular basis of cognitive decline. Methods In total, 110 middle-aged (45-60 y. o.) participants from the Semmelweis Study cohort underwent gait analysis under single- and dual-task conditions, the latter involving a cognitive subtraction task. Dual-task cost (DTC) was defined as the change in gait velocity under DT. Gait variability was assessed via the Gait Variability Index (GVI). Retinal arteriovenous ratio (AVR), measured via fundus photography, was used to assess the status of the microvasculature. Participants were stratified into AVR tertiles, and gait performance was compared between the lowest and highest tertiles. Results Participants in the lowest AVR tertile had higher DTC (−15.5 ± 13%) than those in the highest (−9.5 ± 9.8%, p = 0.03), indicating greater cognitive-motor interference. DT evoked increased gait variability in the low AVR group (GVI: 122.8 ± 16.3 vs. 115.4 ± 11.2, p = 0.03). Conclusions Microvascular dysfunction, as reflected in retinal vessel changes, was associated with dual-task gait impairments. These findings underscore the potential of DT gait testing and retinal imaging as early, non-invasive indicators of VCI, allowing timely preventive interventions. Key messages • Retinal vessel imaging and dual-task gait testing offer non-invasive tools to detect early vascular cognitive impairment (VCI). • Early detection of VCI enables timely interventions to reduce the burden of cognitive impairment in aging populations.