The Brain Health Index: Integrating vulnerability, resilience, and cognitive function into a unified measure of cognitive health and risk of neurodegenerative disease

Abstract

INTRODUCTION: Assessing brain health and identifying cognitive impairment risk remains challenging, with only 11.4% of MCI cases receiving timely diagnoses. We developed the Brain Health Index (BHI), integrating the Vulnerability Index, Resilience Index, and Number Symbol Coding Task into a unified metric. METHODS: We evaluated 469 participants (258 congnitively normal [CN], 140 mild cognitive impairment [MCI], 49 Alzheimer's disease and related dementias [ADRD]) using comprehensive clinical, cognitive, and biomarker assessments. After empirically-derived weighting, BHI thresholds were developed. Cross-sectional associations and longitudinal analyses were performed, with threshold validation for risk stratification. RESULTS: BHI demonstrated strong correlations with cognitive (Montreal Cognitive Assessment [MoCA] r2 = 0.408), functional (Functional Activities Questionnaire [FAQ] r2 = 0.278), and biomarker (neurofilament light chain [NfL] r2 = 0.073) measures. Complete mediation was observed for NfL and glial fibrillary acidic protein (GFAP) changes over 1 year. Threshold analysis revealed 89.2% of low BHI participants had cognitive impairment, with only one ADRD case in the high BHI group. DISCUSSION: The BHI provides a brief, validated, comprehensive brain health metric with clinical utility for risk stratification and intervention monitoring. Highlights: Assessing brain health status and identifying individuals at risk for cognitive impairment remains a significant challenge, particularly in early prodromal and symptomatic stages when current therapies may be most effective and patients may be eligible for clinical trials. We created a unified metric, the Brain Health Index (BHI), combining resilience and vulnerability factors with cognitive performance that divided individuals into high, indeterminant, and low risk groups. The BHI demonstrated strong correlations with cognitive, functional, and biomarker measures. The BHI had a 16-fold increase in identifying individuals who were likely to have cognitive impairment. The BHI provides a brief, validated, comprehensive brain health metric with clinical utility for risk stratification and intervention monitoring.