Mapping creatinine- and cystatin C-related white matter brain deficits in the elderly

Poor kidney function is associated with increased risk of cognitive decline and generalized brain atrophy. Chronic kidney disease impairs glomerular filtration rate, and this deterioration is indicated by elevated blood levels of kidney biomarkers such as creatinine and cystatin C. Here we hypothesized that impaired renal function would be associated with brain deficits in regions vulnerable to neurodegeneration. Using tensor-based morphometry, we related patterns of brain volumetric differences to creatinine, cystatin C levels, and glomerular filtration rate in a large cohort of 738 (mean age, 75.5 ± 6.8 years; 438 men, 300 women) elderly Caucasian subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative. Elevated kidney biomarkers were associated with volume deficits in the white matter region of the brain. All 3 renal parameters in our study showed significant associations consistently with a region that corresponds with the anterior limb of internal capsule, bilaterally. This is the first study to report a marked profile of structural alterations in the brain associated with elevated kidney biomarkers, helping us to explain the cognitive deficits.