Decline in kidney function over the course of adulthood and cognitive function in midlife

Abstract

Objective: To test the hypothesis that end-stage renal disease (ESRD) risk exposure during young adulthood is related to worse cognitive performance in midlife.

Methods: We included 2,604 participants from the population-based Coronary Artery Risk Development in Young Adults (CARDIA) Study (mean age 35 years, 54% women, 45% Black). Estimated glomerular filtration rate and albumin-to-creatinine ratio were measured every 5 years at year (Y) 10 through Y30. At each visit, moderate/high risk of ESRD according to the Kidney Disease: Improving Global Outcomes guidelines (estimated glomerular filtration rate <60 mL/min/1.73 m² or albumin-to-creatinine ratio >30 mg/g) was defined, totaled over examinations, and categorized into 0 episodes, 1 episode, and >1 episodes of ESRD risk. At Y30, participants underwent global and multidomain cognitive assessment. We used analysis of covariance to assess the association of ESRD risk categories with cognitive function, controlling for cardiovascular risk factors.

Results: Over the course of 20 years, 427 participants (16% of the study population) had ≥1 episodes of ESRD risk exposure. Individuals with more risk episodes had lower composite cognitive function (p < 0.001), psychomotor speed (p < 0.001), and executive function (p = 0.007). All these associations were independent of sociodemographic status and cardiovascular risk factors.

Conclusions: In this population-based longitudinal study, we show that episodes of decline in kidney function over the young-adulthood course are associated with worse cognitive performance at midlife. Preserving kidney function in young age needs to be investigated as a potential strategy to preserve cognitive function in midlife.

Figure 1. Definition of ESRD risk categories based on KDIGO guidelines

Green indicates low end-stage renal disease (ESRD) risk; yellow indicates moderately increased risk; orange indicates high risk; and red indicates very high risk. eGFR = estimated glomerular filtration rate; KDIGO = Kidney Disease: Improving Global Outcomes.

Figure 2. Study sample

Flowchart of participant selection from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort for the analysis in this study. DSST = Digit Symbol Substitution Test; MoCA = Montreal Cognitive Assessment; RAVLT = Rey Auditory Verbal Learning Test.

Figure 3. Alluvial plot depicting kidney function trajectories during follow-up

(A) All participants and (B) participants with ≥1 episodes of moderate/high end-stage renal disease (ESRD risk). The y-axis shows ESRD risk categories based on Kidney Disease: Improving Global Outcomes guidelines. Green indicates low risk; yellow indicates moderately increased risk; orange indicates high risk; and red indicates very high risk. The x-axis shows follow-up examinations in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Green lines indicate participants with no episode of ESRD risk; red indicates 1 episode; and black indicates >1 episode of ESRD risk. Thicker lines indicate a higher number of participants with corresponding pattern of change in kidney function. Y = year.

Figure 4. Association between variability in ESRD risk during the follow-up and cognitive function at year 30

Adjusted for age, sex, race, education, center, hypertension, body mass index, total cholesterol, smoking, and diabetes mellitus. Mean (standard error) are presented as difference in z scores of cognitive function. The Stroop test is inverted so that higher values in all cognitive tests reflect better cognitive function. The p values presented are for trend. Cat FLU = category fluency; DSST = Digit Symbol Substitution Test; ESRD = end-stage renal disease; Let FLU = Letter fluency; MoCA = Montreal Cognitive Assessment; RAVLT = Rey Auditory Verbal Learning Test.