Intraindividual difference in estimated GFR by creatinine and cystatin C, cognitive trajectories and motoric cognitive risk syndrome

Background. Intraindividual differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFR(cys)) and creatinine (eGFR(cr)) can convey important clinical information regarding health status. However, the clinical implications of these differences (eGFR(diff)) for risk of cognitive decline and motoric cognitive risk (MCR) syndrome remains unclear. We aimed to investigate the longitudinal associations of eGFR(diff) with cognitive trajectories and incident MCR.Methods. Based on the China Health and Retirement Longitudinal Study, we identified two study subcohorts: one for cognitive trajectory follow-up (6423 participants, 2011-2018) and another for incident MCR follow-up (2477 participants, 2011-2015). The eGFR(diff) was defined as eGFR(cys) - eGFR(cr). Adjusted ordinal and binary logistic regression models were separately used to assess the associations of eGFR(diff) with cognitive trajectories and incident MCR. We also performed discordance analyses for eGFR(diff) versus eGFR(cys), eGFR(cr) or eGFR based on both creatinine and cystatin C (eGFR(cys-cr)).Results. In the first subcohort, four distinct 7-year cognitive trajectories were identified. Each 1 standard deviation (SD) higher eGFR(diff) (value for eGFR(cys) - eGFR(cr)) was associated with a lower risk of poorer cognitive trajectories {odds ratio 0.909 [95% confidence interval (CI) 0.877-0.942]}. In the second subcohort, 121 participants developed incident MCR after a 4-year follow-up. Each 1-SD higher eGFR(diff) (value for eGFR(cys) - eGFR(cr)) 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 eGFR(cys) than eGFR(cr) and eGFR(cys-cr). For the discordance analyses, the 'discordantly high eGFR(diff)/low eGFR' group but not the 'discordantly low eGFR(diff)/high eGFR' exhibited a significantly lower risk of poorer cognitive trajectories and MCR compared with the concordant group.Conclusions. A large negative difference between eGFR(cys) and eGFR(cr) (eGFR(cys) < eGFR(cr)) was associated with a higher risk of cognitive decline and incident MCR. The eGFR(diff) could capture additional valuable risk information beyond eGFR(cys), eGFR(cr) and eGFR(cys-cr).