Structural and functional assessment of the brain in European Americans with mild-to-moderate kidney disease: Diabetes Heart Study-MIND

Background. Advanced chronic kidney disease (CKD) is associated with altered cerebral structure and function. Relationships between mild-to-moderate CKD and brain morphology and cognitive performance were evaluated in European Americans (EAs). Methods. A total of 478 EAs with estimated glomerular filtration rate (eGFR) >= 45 mL/min/1.73 m(2) and urine albumin: creatinine ratio (UACR) < 300 mg/g, most with type 2 diabetes (T2D), were included. Measures of total intracranial volume (TICV), cerebrospinal fluid volume, total white matter volume (TWMV), total gray matter volume (TGMV), total white matter lesion volume (TWMLV), hippocampal white matter volume (HWMV) and hippocampal gray matter volume (HGMV) were obtained with magnetic resonance imaging. Cognitive testing included memory (Rey Auditory Visual Learning Test), global cognition (Modified Mini-Mental State Examination) and executive function (Stroop Task, Semantic Fluency, Digit Symbol Substitution Test). Associations with CKD were assessed using log-transformed eGFR and UACR, adjusted for age, sex, body mass index, smoking, hemoglobin A1c, blood pressure, diabetes duration, cardiovascular disease and education. Results. Participants were 55.2% female, 78.2% had T2D; mean +/- SD age 67.6 +/- 9.0 years, T2D duration 16.4 +/- 6.5 years, eGFR 92.0 +/- 22.3 mL/min/1.73 m(2) and UACR 23.8 +/- 39.6 mg/g. In adjusted models, eGFR was negatively associated with TICV only in participants with T2D [parameter estimate (beta): -72.2, P = 0.002]. In non-diabetic participants, inverse relationships were observed between eGFR and HGMV (beta: -1.0, P = 0.03) and UACR and normalized TWMLV (beta: -0.2, P = 0.03). Kidney function and albuminuria did not correlate with cognitive testing. Conclusions. In EAs with mild CKD enriched for T2D, brain structure and cognitive performance were generally not impacted. Longitudinal studies are necessary to determine when cerebral structural changes and cognitive dysfunction develop with progressive CKD in EAs.