Brain Health Deviation Index: A Comprehensive Brain Health Assessment Biomarker for Predicting Cognitive Decline and Polyvascular Stenosis

ABSTRACT Assessing and quantifying brain health remains a pressing challenge, despite its importance for overall well‐being. Traditional methods that focus on isolated brain measures often fail to capture the multifaceted nature of brain health and may miss early signs of dysfunction. In response, there is a growing need for sophisticated, data‐driven approaches to comprehensively evaluate brain health. This study introduces a novel neuroimaging‐based biomarker called the Brain Health Deviation Index (BHDI). BHDI integrates various brain metrics, including brain age gap, white matter volume, hippocampal volume, brain resilience, and fractional anisotropy, to provide a personalized evaluation of brain health. The researchers employed cross‐sectional data from the community‐based PRECISE cohort ( N = 1806) and longitudinal data from the MAS dataset ( N = 453) to investigate the association between BHDI, polyvascular stenosis, and cognitive decline. The findings revealed a robust correlation between higher BHDI scores and an increased risk of polyvascular stenosis in the PRECISE cohort. Specifically, individuals in the high‐risk BHDI group had significantly higher odds of intracranial artery stenosis (OR = 3.170, 95% CI 1.951–5.149, p < 0.001), extracranial artery stenosis (OR = 3.839, 95% CI 1.496–9.848, p < 0.001), coronary artery stenosis (OR = 2.793, 95% CI 2.045–3.816, p < 0.001), and systemic artery stenosis (OR = 2.785, 95% CI 2.078–3.734, p < 0.001) compared to the low‐risk group. In the longitudinal MAS dataset, higher BHDI scores were also associated with a greater risk of cognitive decline and progression to dementia (OR = 4.139, 95% CI 1.251–13.700) among healthy individuals. The Brain Health Deviation Index is a promising non‐invasive neuroimaging biomarker that showcases the potential to redefine brain health assessment. Its comprehensive validation in diverse community cohorts positions BHDI as an innovative tool for predicting polyvascular stenosis and cognitive decline, with potential applications in clinical brain health monitoring. This study represents a significant step toward a more holistic approach to evaluating brain well‐being.