Reduced neurovascular coupling is associated with increased cardiovascular risk without established cerebrovascular disease: A cross-sectional analysis in UK Biobank

Mid-life vascular risk factors predict late-life cerebrovascular diseases and poor global brain health. Although endothelial dysfunction is hypothesized to contribute to this process, evidence of impaired neurovascular function in early stages remains limited. In this cross-sectional study of 31,934 middle-aged individuals from UK Biobank without established cerebrovascular disease, the overall 10-year risk of cardiovascular events was associated with reduced neurovascular coupling (p < 2 × 10^-16) during a visual task with functional MRI, including in participants with no clinically apparent brain injury on MRI. Diabetes, smoking, waist-hip ratio, and hypertension were each strongly associated with decreased neurovascular coupling with the strongest relationships for diabetes and smoking, whilst in older adults there was an inverted U-shaped relationship with DBP, peaking at 70-80 mmHg DBP. These findings indicate that mid-life vascular risk factors are associated with impaired cerebral endothelial-dependent neurovascular function in the absence of overt brain injury. Neurovascular dysfunction, measured by neurovascular coupling, may play a role in the development of late-life cerebrovascular disease, underscoring the need for further longitudinal studies to explore its potential as a mediator of long-term cerebrovascular risk.