RESUMO
BACKGROUND: Intraindividual differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) can convey important clinical information regarding the health status. However, the clinical implications of these differences (eGFRdiff) for risk of cognitive decline and motoric cognitive risk syndrome (MCR) remains unclear. We aimed to investigate the longitudinal associations of eGFRdiff with cognitive trajectories and incident MCR. METHODS: Based on the China Health and Retirement Longitudinal Study, we identified two study sub-cohorts: one for cognitive trajectory follow-up (6423 participants; years:2011-2018) and another for incident MCR follow-up (2477 participants; years:2011-2015). The eGFRdiff was defined as eGFRcys minus eGFRcr. Adjusted ordinal and binary logistics regression models were separately used to assess the associations of eGFRdiff with cognitive trajectories and incident MCR. We also performed discordance analyses for eGFRdiff vs eGFRcys, eGFRcr or eGFR based on both creatinine and cystatin C (eGFRcys-cr). RESULTS: In the first sub-cohort, four distinct 7-year cognitive trajectories were identified. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was associated with a lower risk of poorer cognitive trajectories (OR: 0.909, 95% CI: 0.877-0.942). In the second sub-cohort, 121 participants developed incident MCR after a 4-year follow-up. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was linked with a 25.3% (95%CI: 16.6%-33.2%) decreased risk for MCR. The above associations persisted in individuals with normal kidney function. Additionally, the risk for cognitive decline and incident MCR was more strongly associated with eGFRcys than eGFRcr and eGFRcys-cr. For the discordance analyses, 'discordantly high eGFRdiff/low eGFR' group, but not 'discordantly low eGFRdiff/high eGFR', exhibited a significantly lower risk of poorer cognitive trajectories and MCR compared to the concordant group. CONCLUSIONS: A large negative difference between eGFRcys and eGFRcr (eGFRcys lower than eGFRcr) was associated with higher risk of cognitive decline and incident MCR. The eGFRdiff could capture additional valuable risk information beyond eGFRcys, eGFRcr, and eGFRcys-cr.