Chronic kidney disease biomarkers, cognitive impairment and incident dementia in an older healthy cohort

Background: Chronic kidney disease is a risk factor for cognitive impairment (CI),but reports of individual associations of estimated glomerular filtration rate (eGFR) and albuminuria with CI and incident dementia in healthier older longitudinal populations are lacking. Our goal was to estimate these associations in a large cohort of older healthy persons. Methods: In a longitudinal cohort study of older persons without prior cardiovascular disease, we estimated the associations between baseline eGFR (in mL/min per 1.73 m2) and albuminuria, measured as urine albumin-to-creatinine ratio (UACR, in mg/mmol) and cognitive test scores, declines in cognitive test scores and incident dementia, using adjusted linear and linear mixed models. Cox proportional hazards regression models assessed the association between baseline kidney function and incident CI no dementia (CIND) or dementia at a median of 4.7 years. Results: At baseline, among 18,131 participants, median age was 74 years, eGFR 74 (IQR 63, 84), UACR 0.8 (IQR 0.5, 1.5; (7.1 (4.4- 13.3 mg/g and 56% were female. Baseline eGFR was not associated with performance on any cognitive tests in cross-sectional analysis, nor incident CIND or dementia over median follow-up of 4.7 years. However, baseline UACR ≥ 3 (≥ 26.6 mg/g) was significantly associated with lower baseline scores and larger declines on the Modified Mini Mental State Exam, verbal memory and processing speed tests, and with incident CIND [(hazard ratio, HR, 1.19; 95% confidence interval, CI,1.07 - 1.33)] and dementia (HR 1.32;1.06 - 1.66). Conclusion: Mild albuminuria was associated with worse baseline cognitive function, cognitive decline, and increased risk for incident CIND and dementia. Screening global cognitive tests for older persons with UACR ≥ 3 mg/mmol could identify those at elevated risk of cognitive decline and dementia.