Background: Cognitive aging has been underexplored in midlife across diverse populations. We investigated average cognitive change during midlife (aged 40-65), its predictors and whether these associations differ by race/ethnicity.

Methods: We conducted a pooled analysis of 3,750 participants (62% non-Hispanic White [NHW], 28% Black, 10% Hispanic; 65% female) from three US cohorts: Wisconsin Registry for Alzheimer’s Prevention, Health and Aging Brain Study-Health Disparities, and Coronary Artery Risk Development in Young Adults Study. The median age was 56 (Q1-Q3: 52-59) at baseline, with a median follow-up of 5 (Q1-Q3: 4.0-6.1) years. We harmonized cognitive scores across three domains (executive function, memory, and language) using confirmatory factor analysis, accounting for differential item functioning by interview language. Associations of sociodemographics and baseline cardiovascular risk factors (CVRFs: hypertension, diabetes, obesity, high cholesterol, and smoking) with standardized annual cognitive change were evaluated using linear regression, with racial/ethnic differences assessed through interactions and stratified analyses.

Results: Mean annual cognitive changes during midlife in executive function, memory and language were -0.11±0.25, -0.04±0.21, and -0.01±0.15 SD, respectively. Older adults had faster decline in all domains, while female participants and those with higher education had slower decline in executive function and memory. The patterns of decline differed across race/ethnicity (Figure 1). Compared with NHW participants, Hispanic participants declined faster in executive function (-0.38, 95%CI -0.40 to -0.36), memory (-0.12, 95%CI -0.15 to -0.10) and language (-0.04, 95%CI -0.06 to -0.02); Black participants declined faster in executive function (-0.04, 95%CI -0.06 to -0.03) and memory (-0.04, 95%CI -0.05 to -0.02), and these differences were not explained by education and CVRFs. Among all participants, diabetes was associated with faster decline in executive function (-0.04, 95%CI -0.06 to -0.02) and language (-0.02, 95%CI: -0.03 to -0.0004). Among racial/ethnic groups, diabetes was associated with faster decline in NHW (executive function: -0.03, 95% CI -0.06 to -0.01; language: -0.03, 95% CI -0.05 to -0.001) and Black participants (executive function: -0.04, 95%CI: -0.06 to -0.01; Figure 2).

Conclusion: Racial/ethnic differences in cognitive trajectories emerge during midlife, particularly in executive function and memory. CVRFs may affect midlife cognitive change differently across racial and ethnic groups.