Higher Levels of Cystatin C Are Associated with Worse Cognitive Function in Older Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Cognitive Study

Abstract

OBJECTIVES Cystatin C, a measure of kidney function, has been linked to cognitive impairment, but the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD) is unknown. DESIGN/SETTING/PARTICPANTS We studied 821 participants from the Chronic Renal Insufficiency Cohort Cognitive Study with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement. MEASUREMENTS Levels of serum cystatin C were categorized into tertiles; cognitive function was assessed with six neuropsychological tests. We compared scores on these tests across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and poor cognitive performance (1 SD difference from the mean). RESULTS The mean participant age was 64.9 years, 50.6% were male, and 48.6% were white. After multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the 3MS, Buschke Delayed Recall, Trails A, Trails B, and Boston Naming (p<0.05 for all). This association remained statistically significant for Buschke Delayed Recall (p=0.01) and Trails A (p=0.03) after additional adjustment for eGFR. Compared to the lowest tertile of cystatin C, the highest tertile was associated with increased likelihood of poor cognitive performance on Trails A (OR=2.17; 95% CI: 1.16-4.06), Trails B (OR=1.89; 95% CI: 1.09-3.27), and Boston Naming (OR=1.85; 95% CI: 1.07-3.19) after multivariate adjustment in logistic models. CONCLUSION Among patients with CKD, higher levels of serum cystatin C were associated with worse cognition and increased likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of eGFR levels.

Neurological complications in chronic kidney disease

“…5 It is hypothesized that cystatin-C may contribute to neurodegeneration through amyloid plaque formation although further longitudinal studies are required. 5 …”

Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT)

“…4,5 Given this cerebrovascular disease burden, it is not surprising that cognitive impairment is common in individuals with CKD, particularly in older adults. 6–10 Many of the studies exploring the association between CKD and cognitive function relied on omnibus cognitive screening instruments rather than more detailed neurocognitive testing, lacked brain imaging, or did not have concurrent ascertainment of cognitive functioning and both kidney disease markers. 11–14 One study using a cognitive screening test noted that, when eGFR was preserved, albuminuria was associated independently with incident cognitive impairment, while, when albuminuria was minimal, low eGFR was associated independently with cognitive impairment.…”

Chronic kidney disease‐related physical frailty and cognitive impairment: a systemic review

“…In individuals with CKD, higher serum cystatin C levels were associated with worse cognition, incident cognitive decline and cognitive and physical disability . Moreover, the cognition decline induced by cystatin C may be independent of eGFR . High cystatin C levels were associated with poor global cognition and higher white matter deficits in the anterior limb of the internal capsule .…”

“…112,113 Moreover, the cognition decline induced by cystatin C may be independent of eGFR. 114 High cystatin C levels were associated with poor global cognition and higher white matter deficits in the anterior limb of the internal capsule. 115 Several lines of evidence also support a role for cystatin C in the neurodegenerative pathways associated with amyloid plaque formation, as demonstrated by its colocalization with -amyloid in brain tissue and a high correlation with the beta-amyloid and tau levels in the cerebrospinal fluid.…”