A total of 825 participants were recruited into the CRIC COG Study (of those who were eligible, 983 were asked to participate). This cohort had a mean (SD) age of 64.9 (5.6) years and was 50% male and 45% Black. Site enrollment included 205 participants from the University of Pennsylvania center, 223 participants from the Case Western Reserve center, 196 from the University of Illinois at Chicago center, and 201 from the Kaiser Permanente of Northern California/University of California San Francisco center. At the time of cognitive testing, mean (SD) eGFR was 41.0 (14.3) ml/min/1.73 m2 with 80 participants having an eGFR ≥ 60 (mean 61) ml/min/1.73 m2, 289 with eGFR 45-59 (mean 49) ml/min/1.73 m2, 299 with eGFR 30-44 (mean 37) ml/min/1.73 m2 and 157 with eGFR <30 (mean 24) ml/min/1.73 m2. The characteristics of the CRIC COG participants were compared across eGFR category (). Participants with lower eGFR tended to be older, have less educational attainment and greater comorbidity burden including diabetes and hypertension.
Characteristics of the 825 Participants Enrolled in the CRIC Cognitive Function Study.
In unadjusted analyses, for each of the cognitive tests, a consistent pattern of worse cognitive scores in participants with greater CKD severity was observed. For example, for the 3MS test, participants with eGFR ≥ 60 ml/min/1.73 m2 had a mean (SD) score of 95.2 (5.0), those with eGFR 45-59 ml/min/1.73 m2 had a score 94.0 (7.6), those with eGFR 30-44 ml/min/1.73 m2 had a score 92.1 (7.1) and those with eGFR <30 ml/min/1.73 m2 had a score of 91.4 (7.8) (p<0.001 for trend). For the Trails B test, mean (SD) scores were 116 (70), 126 (70), 151 (83) and 164 (85), respectively (p<0.001 for trend). A similar pattern emerged for the other four cognitive tests (5 subscores). Multivariable adjustment for age, gender, race, education, BMI, diabetes, hypertension, and depression did not alter the findings with the exception of the Category Fluency and Buschke tests ().
Adjusted Mean Cognitive Function Score by Baseline Level of eGFR (Adjusted for Age, Race, Education, Gender, Diabetes, Hypertension, BMI and Depression).
We next determined the association between severity of CKD and clinically significant cognitive impairment defined as a score 1 SD or more severe from the mean (). Participants with more severe CKD had higher prevalence of cognitive impairment on global cognition (22% for eGFR<30 ml/min/1.73 m2, 14% for eGFR 30-44 ml/min/1.73 m2, 10% for eGFR 45-59 ml/min/1.73 m2, 5% for eGFR ≥60 ml/min/1.73 m2, p<0.001 for trend), on attention (20%, 17%, 9%, 4%, respectively, p<0.001), on executive function (28%, 23 %, 12%, 11%, respectively, p<0.001), naming (24%, 20%, 13%, 8%, respectively, p<0.001), on category fluency (17%, 15%, 13%, 5%, respectively, p=0.02), and on delayed memory (19%, 17%, 13%, 5%, respectively, p=0.003). While this pattern was also evident for the test of immediate memory (22%, 22%, 17%, 19%, respectively, p=0.16), the differences were not statistically significant. After multivariable adjustment for age, gender, race, education, hypertension, depression, BMI, and diabetes, participants with more severe CKD continued to demonstrate greater likelihood of cognitive impairment on most tests (). Compared with persons who had mild or moderate CKD (eGFR 45-59), participants with advanced CKD (eGFR <30) were more likely to have cognitive impairment on tests of global cognition (adjusted odds ratio [OR] 2.0, 95% CI 1.1 to 3.9), naming (OR 1.9, 95% CI 1.0 to 3.3), attention (OR 2.4, 95%CI 1.3 to 4.5), executive function (OR 2.5, 95% CI 1.9 to 4.4) and delayed memory (OR=1.5, 95%CI 0.9 to 2.6) but not on category fluency (OR=1.1, 95% CI 0.6 to 2.0) or immediate memory (OR= 1.2, 95% CI 0.7 to 2.1).
Prevalence and Unadjusted Odds Ratios of Clinically Significant Cognitive Impairment, by eGFR Group.
Figure The likelihood of cognitive impairment (adjusted odds ratios and 95% confidence intervals) across eGFR category (reference group is 45-59 ml/min/1.73m2). Models were adjusted for age, gender, race, education, diabetes, hypertension, BMI, and depression. (more ...)
In subgroup analyses defined a priori by a diagnosis of diabetes or not, race (black compared to white) and gender, we did not observe consistent interactions for these strata (p>0.1 for all) and the association between level of eGFR and cognitive function. We also stratified the cohort by ages 55-64, 65-74 and ≥75 years and found that the prevalence of global cognitive impairment (defined by 3MS) was 9.1%, 18.4% and 13.3% respectively, but there was no interaction by age on the association between CKD severity and cognitive function.