Albuminuria, cognitive functioning, and white matter hyperintensities in homebound elders

Abstract

Background: Albuminuria, a kidney marker of microvascular disease, may herald microvascular disease elsewhere, including in the brain.

Study design: Cross sectional.

Setting & participants: Boston, MA, elders receiving home health services to maintain independent living who consented to brain magnetic resonance imaging.

Predictor: Urine albumin-creatinine ratio (ACR).

Outcome: Performance on a cognitive battery assessing executive function and memory by using principal components analysis and white matter hyperintensity volume on brain imaging, evaluated in logistic and linear regression models.

Results: In 335 participants, mean age was 73.4 +/- 8.1 years and 123 participants had microalbuminuria or macroalbuminuria. Each doubling of ACR was associated with worse executive function (beta = -0.05; P = 0.005 in univariate and beta = -0.07; P = 0.004 in multivariable analyses controlling for age, sex, race, education, diabetes, cardiovascular disease, hypertension, medications, and estimated glomerular filtration rate [eGFR]), but not with worse memory or working memory. Individuals with microalbuminuria or macroalbuminuria were more likely to be in the lower versus the highest tertile of executive functioning (odds ratio, 1.18; 95% confidence interval, 1.06 to 1.32; odds ratio, 1.19; 95% confidence interval, 1.05 to 1.35 per doubling of ACR in univariate and multivariable analyses, respectively). Albuminuria was associated with qualitative white matter hyperintensity grade (odds ratio, 1.13; 95% confidence interval, 1.02 to 1.25; odds ratio, 1.15; 95% confidence interval, 1.02 to 1.29 per doubling of ACR) in univariate and multivariable analyses and with quantitative white matter hyperintensity volume (beta = 0.11; P = 0.007; beta = 0.10; P = 0.01) in univariate and multivariable analyses of log-transformed data. Results were similar when excluding individuals with macroalbuminuria.

Limitations: Single measurement of ACR, indirect creatinine calibration, and reliance on participant recall for elements of medical history.

Conclusions: Albuminuria is associated with worse cognitive performance, particularly in executive functioning, as well as increased white matter hyperintensity volume. Albuminuria likely identifies greater brain microvascular disease burden.

Figure 1

Executive functioning in tertiles from poorest to best stratified by the presence of micro- or macroalbuminuria as compared to non-albuminuric participants. Numbers within bars represent the number of participants within each group. P for trend = 0.02.

Figure 2

Distribution of white matter hyperintensity grades by the presence of micro- or macroalbuminuria as compared to non-albuminuric participants. Numbers within bars represent the number of participants within each group. P for trend = 0.02.