Background: Chronic kidney disease is associated with cognitive impairment and increased Alzheimer’s disease (AD) risk in older adults. However, most studies focus on adults aged 65 and older or those with diagnosed kidney disease. We examined whether kidney function in early to midlife is associated with cognitive performance.

Methods: We analyzed Wave V (ages 33–43) and Wave VI (ages 39–51) data from the National Longitudinal Study of Adolescent to Adult Health. Kidney function was assessed with estimated glomerular filtration rate, using 2021 CKD-EPI equations with creatinine and cystatin C (eGFRCr-Cys) and creatinine alone (eGFRCr). Cognitive performance at Waves V and VI included immediate and delayed recall, backward digit span, and a principal components–derived summary score (PC Score Cognition). Survey-weighted linear regression was adjusted for age, sex, race, education, BMI, high cholesterol, diabetes, hypertension, smoking, alcohol use, and pregnancy.

Results: In cross-sectional Wave V analyses (n=589), eGFRCr-Cys was positively associated with all cognitive measures (Figure 1). Fully adjusted associations were slightly reduced and were statistically significant for PC Score Cognition and Immediate Recall. Corresponding associations with eGFRCr were positive, but confidence intervals included the null. Restricting analyses to participants with normal to mildly impaired kidney function (n=491) attenuated effect estimates, suggesting lower kidney function drove observed relationships. Wave V eGFR was associated with Wave VI cognitive performance (PC Score Cognition β=0.03; 95%CI: -0.06, 0.12).

Conclusions: eGFRCr-Cys was strongly associated with cognitive performance in early midlife; a 10 ml/min/1.73m2 lower eGFR corresponded to a 0.07 SD lower cognitive score. These findings suggest that reduced kidney function, even without clinical disease, is linked to cognitive performance in early midlife and may represent a novel early biomarker for future risk of AD.