Education Moderates the Biomarker-Cortical-Thickness Relationship in Females With Cognitive Decline: A Descriptive Study With Sex Comparisons

초록

Background and Purpose Education is a well-established proxy for cognitive reserve and hence may influence the relationship between Alzheimer's disease pathology and brain structure. This is particularly relevant in South Korea, where historical sex disparities in educational level among current elderly populations create unique cohort characteristics. This study examined how educational level moderates the biomarker-cortical-thickness relationship in females with cognitive decline, with descriptive sex comparisons used to contextualize these findings within a cohort reflecting disparities in the history of educational opportunities in South Korea. Methods In 80 patients (58 females, 22 males) with cognitive decline, we assessed plasma amyloid-(3 42 (A(342), phosphorylated tau 181 (p-tau), and total tau levels, p-tau/A(342 ratio, regional cortical thickness, and scores on the Mini-Mental State Examination. Given the substantial confounding between sex and educational level in this cohort, moderated mediation analyses examining the biomarker-cortical-thickness-cognition pathway were restricted to females (n=53 with complete data). Results Females had a higher p-tau/A(342 ratio (p=0.026) and thicker frontal cortex (p=0.049) despite the absence of a significant difference in age-adjusted cognition. No significant sex & times; educational level interaction was observed for the biomarkers or cognition. In females, educational level moderated the relationship between the p-tau/A(342 ratio and cortical thickness (p<0.05 in all five brain regions), with high-educational level females showing the expected cortical thinning with pathology, while low-educational level females exhibited preserved thickness, which did not mediate the cognitive performance. Conclusions Descriptive sex comparisons revealed a higher biomarker burden yet greater cortical thickness in females. Importantly, educational level significantly moderated the biomarker-cortical thickness relationship specifically in females, with lower-educated individuals showing structural preservation despite the presence of pathology. These findings suggest that measurements of the cortical thickness can underestimate the disease burden in lower-educated females, which highlights the need for educational level-stratified interpretations of structural biomarkers.

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