Biological embedding of educational disparities in aging and neurodegeneration across global settings

BACKGROUND: While education is crucial for brain health, evidence mainly relies on individual measures of years of education (YoE), neglecting educational quality (EQ). Whether YoE and EQ have complementary impacts on aging and dementia is unknown. METHODS: We assessed the impact of EQ and YoE on brain health in 7,533 subjects from 20 countries, including healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). EQ was based on country-level quality indicators. After applying neuroimage harmonization, we examined their effect on gray matter volume and functional connectivity. Regression models were adjusted for age, sex, and cognition, controlling for multiple comparisons. The impact of image quality was controlled through sensitivity analysis. RESULTS: Less EQ and YoE were associated with greater brain burden across groups. However, EQ had a stronger impact, mainly targeting the vulnerable areas of each condition. At the whole-brain level, EQ influenced atrophy (HCs: ∆mean = 2.0 [1.9-2.0] CL95 × 10⁻², p < 10⁻⁵; AD: ∆mean = 0.1 [-0.0-0.3] CL95 × 10⁻², p = 0.18; FTLD: ∆mean = 3.5 [3.0-4.0] CL95 × 10⁻², p < 10⁻⁵) and networks (HCs: ∆mean = 13.5 [13.2-13.7] CL95 × 10⁻², p < 10⁻⁵; AD: ∆mean = 5.9 [5.2-6.7] CL95 × 10⁻², p < 10⁻⁵; FTLD: ∆mean = 13.2 [11.2-13.7] CL95 × 10⁻², p < 10⁻⁵), 1.3 to 7.0 times more than YoE. CONCLUSION: Results support the need to incorporate education quality to study and improve brain health, underscoring the importance of country-level measures.