Of the 3,030 participants, 445 (15%) had high, 1008 (33%) had intermediate and 1577 (52%) had low cystatin-C with a median level of 1.0 mg/L. Participants with higher cystatin-C level were more likely to be older, white, male, have a higher BMI and CRP and more likely to have hypertension, diabetes, or stroke ().
Baseline Characteristics of the Health ABC Participants by Cystatin-C group.
Elders with higher cystatin-C lhad worse baseline 3MS score (91.4 ± 8.3 vs 92.4 ± 8.4 and 92.4 ± 7.6 for high, intermediate and low cystatin-C, p=0.01) and DSST score (33.6 ± 14.4 vs 35.6 ± 15.0 and 35.4 ± 14.6, p=0.02). Adjustment for age, race, sex, education, baseline cognitive score, BMI, CRP level, hypertension, diabetes, and stroke led to similar results for 3MS but reduced the statistical significance for DSST (p=0.16). Over the 7 years of follow-up, those with high cystatin-C level had greater decline on 3MS (2.7 points vs 1.0 and 0.9 points for the intermediate and low groups, p=0.002) and on DSST (5.5 points vs 4.7 and 3.8 points, p=0.04). Multivariate adjustment led to similar results (3MS, p=0.001 and DSST, p=0.04) (). The rate of loss to follow-up for repeated cognitive testing was 10%; those without follow-up were older, less educated, more likely to be male, had more comorbidities and had slightly higher cystatin-C (p<0.001). The incidence of cognitive impairment on the 3MS was greatest among those with high cystatin-C (38%, OR=1.90; 95%CI 1.42-2.56), but similar among those with intermediate (27%; OR=1.13; 95%CI 0.91-1.42) and low cystatin-C (25%; referent) (). Similarly, the incidence of cognitive impairment on DSST was greatest for high cystatin-C (38%, OR=1.71; 95% CI 1.25-2.32) and somewhat higher for intermediate level(31%, OR= 1.25; 95% CI 1.00-1.55) compared to low level (26%). Multivariate adjustment led to similar results.
Figure 1 Mixed model predicted 3MS and DSST score as a function of cystatin-C level, adjusted for age, race, gender, education, baseline cognitive score, body mass index, C-reactive protein, hypertension, diabetes, and stroke. Error bars indicate 95% confidence (more ...)
The likelihood of developing cognitive impairment over 7 years of follow-up by cystatin-C level.
In order to determine if the association between cystatin-C and cognitive decline was modified by sex, race or APOE e4 status, we added interaction terms to the random effects models but none were statistically significant (all p>0.1). We determined if the association between cystatin-C and incident impairment was evident only among elders with worse kidney function by stratifying the cohort based on eGFR< 60 or ≥60. Participants with high cystatin-C and with eGFR <60 had a roughly two-fold increase in likelihood of developing cognitive impairment compared to those with low level (3MS, 39% vs 22% OR= 2.27; 95% CI 1.22-4.23 and DSST, 36% vs 24% OR=1.78; 95% CI 0.94- 3.39). Interestingly, for those with high cystatin-C and with eGFR ≥ 60, the likelihood of developing cognitive impairment was also increased about 2-fold (3MS, 36% vs 25% OR=1.72; 95% CI 1.04-2.84 and DSST, 42% vs 27% OR=2.01; 95% CI 1.23- 3.29).