Association of albuminuria with white matter hyperintensities volume on brain magnetic resonance imaging in elderly Japanese ― the Hisayama study ―

Background: Both chronic kidney disease and brain white matter hyperintensities (WMH) are known to be risk factors of dementia and mortality. Methods and Results: In 2012, 1,214 community-dwelling Japanese subjects aged ≥65 years underwent brain magnetic resonance imaging (MRI) scans and a comprehensive health examination. This study investigated associations of the urinary albumin: creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) with the WMH volume to intracranial volume (WMHV: ICV) ratio, and the association of the combination of UACR and the WMHV: ICV ratio with cognitive decline and mortality risk. The geometric mean of the WMHV: ICV ratio was 0.223% in the entire study population, and increased significantly with higher UACR levels after adjusting for potential confounding factors (0.213% for normoalbuminuria, 0.248% for microalbuminuria, and 0.332% for macroalbuminuria; Ptrend=0.01). In contrast, there was no clear association between eGFR and the WMHV: ICV ratio. Compared with subjects with normoalbuminuria and a smaller WMHV: ICV ratio (<0.257% [median]), subjects with albuminuria and a larger WMHV: ICV ratio (≥0.257%) had higher probabilities of cognitive decline at baseline and all-cause death during the follow-up. Conclusions: This study suggests that subjects with albuminuria have a greater risk of WMH enlargement and that the combination of albuminuria and WMH enlargement increases the risk of cognitive decline and all-cause mortality in an elderly Japanese population.