Comprehensive allostatic load risk index is associated with increased frontal and left parietal white matter hyperintensities in mid-life cognitively healthy adults

Abstract

Abstract To date, there is a lack of universally agreed values to calculate an Allostatic Load (AL) index and a considerable heterogeneity of methods. In this study we propose a comprehensive algorithm that integrates several approaches and generate risk categories to assess associations between AL and brain structure deterioration. In a cohort of cognitively normal mid-life adults (n = 620, age 51.3 ± 5.48 years), we developed a comprehensive composite for AL scoring incorporating gender and age differences, high quartile approach, up-to-date clinical reference values, and current medications, enabling us to then categorize individuals as no-risk, low-risk, medium-risk and high-risk of AL. Compared to the empirical approach, the comprehensive composite showed better model fit criteria and a strong association with gender. AL categories were regressed against Magnetic Resonance Imaging brain volume and white matter hyperintensity (WMH) measurements. Higher AL risk categories were associated with increased total, periventricular, frontal, and left parietal WMH volumes. This suggests that sustained stress exposure enhances brain deterioration in mid-life adults, potentially accelerating later development of cognitive decline and dementia. Showing better model fit than the classical approaches, our comprehensive algorithm can provide a more accurate AL estimation to explore how stress exposure enhances age-related health decline.