Vascular risk factors and cognitive impairment in chronic kidney disease: the Chronic Renal Insufficiency Cohort (CRIC) study

Abstract

Background and objectives: Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear.

Design, setting, participants, & measurements: We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score>1 SD below the mean score.

Results: Among 3591 participants, the mean age was 58.2±11.0 years, and the mean estimated GFR (eGFR) was 43.4±13.5 ml/min per 1.73 m2. Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR<30 ml/min per 1.73 m2 was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m2. This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders.

Conclusions: The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia.

Figure 1.

Distribution of Modified Mini-Mental State Exam (3MS) scores among CRIC participants.

Figure 2.

Association of estimated GFR with cognitive impairment in unadjusted and adjusted models among 3591 CRIC participants. The bars indicate 95% confidence intervals. Referent category is eGFR 45 to 59 ml/min per 1.73 m². An asterisk indicates P < 0.05. P for linear trend across eGFR strata = <0.0001, 0.059, 0.063, and 0.052 in the unadjusted, demographics adjusted, traditional vascular risk factor adjusted, and fully adjusted models, respectively. CVD, cardiovascular disease; CV, cardiovascular. ^†Model adjusted for eGFR, age, sex, race, ethnicity, education, stroke, and CRIC clinical site. ^‡Model adjusted for eGFR, age, sex, race, ethnicity, education, stroke, diabetes, hypertension, smoking, history of elevated cholesterol, coronary heart disease, peripheral arterial disease, and CRIC clinical site. ^††Model adjusted for eGFR, age, sex, race, ethnicity, education, stroke, hemoglobin, and CRIC clinical site.