Educational attainment is associated with reduced functional decline in Puerto Ricans with elevated pTau181

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 ε4, 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 (<mean-1SD) was analyzed. Functional scores were derived from the Clinical Dementia Rating scale (CDR-FUNC). The primary analysis examined educational attainment (EA; high ≥12 years versus low <12 years) as a categorical proxy for CR. Nonparametric tests compared CDR-FUNC across EA and APOE ε4 strata. A secondary analysis applied a hurdle model, examining years of education as a continuous predictor on (1) the odds of any impairment (CDR-FUNC > 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 × APOE ε4 interaction was observed, though a negative trend suggested that increasing education attenuated ε4-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 ε4 may worsen outcomes with decreasing education, suggesting both educational and genetic factors should inform strategies to mitigate cognitive decline globally.