Abstract
Background: Education promotes cognitive reserve (CR), potentially buffering Alzheimer's disease pathology (ADP). However, the education-CR relationship may differ by population and genetic background. Objective: To examine education, APOE epsilon 4, and functional scores in a Puerto Rican (PR) cohort with varying plasma pTau181, an ADP biomarker. Methods: A subset of 514 PR older adults with "high" (>mean+1SD) or "low" pTau181 ( 0) and (2) severity among impaired participants, adjusting for age and sex. Results: High EA was associated with better CDR-FUNC than low EA within the high pTau181 group (n = 80; Median(Low_)EA = 7, Median(High_)EA = 0; p = 0.011). The hurdle model similarly showed that each additional year of education reduced the odds of any functional impairment in the high-pTau181 group (OR = 0.89, 95% CI [0.79-0.99]). No significant education x APOE epsilon 4 interaction was observed, though a negative trend suggested that increasing education attenuated epsilon 4-related impairment. Conclusions: Greater education is linked to functional preservation in PR older adults, particularly in those with elevated ADP, suggesting potential CR-mediated resilience. APOE epsilon 4 may worsen outcomes with decreasing education, suggesting both educational and genetic factors should inform strategies to mitigate cognitive decline globally.