Albuminuria, Cognitive Functioning, and White Matter Hyperintensities in Homebound Elders

doi:10.1053/j.ajkd.2008.08.022

American Journal of Kidney Diseases

Volume 53, Issue 3, March 2009, Pages 438-447

https://doi.org/10.1053/j.ajkd.2008.08.022 Get rights and content

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 (β = −0.05; P = 0.005 in univariate and β = −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 (β = 0.11; P = 0.007; β = 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.

Section snippets

Study Population

Detailed methods for the Nutrition, Aging, and Memory in Elders (NAME) Study have been described.¹⁷ Between 2003 and 2007, participants were recruited at 4 Boston-area home care agencies that provide services to make home living possible for elders. Eligible individuals were at least 60 years old and had low income (determined by the state), diminished ability to perform activities of daily living, and an unmet need in a critical area including food or personal care. NAME exclusion criteria

Results

For 335 participants, mean age was 73.4 ± 8.1 years (Table 1). Median ACR was 11.6 mg/g (25% to 75%, 5.9 to 46.3 mg/g). There were 212 (63.3%), 103 (30.8%), and 20 (6.0%) with ACR within ranges consistent with normoalbuminuria, microalbuminuria, and macroalbuminuria. Overall, participants had substantial physical impairment, with 71.3% having at least “some difficulty” on 1 or more activity of daily living.

Discussion

The findings in the present study show that the presence of albumin in urine, even at levels consistent with microalbuminuria, is independently associated with cognitive impairment. Specifically, albuminuria is associated with impaired executive functioning, manifest by impaired mental processing speed, planning and sequencing of events, and ability to complete unstructured tasks. This type of deficit is consistent with pathological states in subcortical brain pathways and may result from

Acknowledgements

Preliminary data from this study were presented in abstract form at the Annual Meeting of the American Society of Nephrology, November 1-5, 2007, in San Francisco, CA. The authors thank the entire NAME team, particularly the researchers who visited Boston elders in their homes to perform the cognitive testing, the home care agencies that allowed us access to their clients, and the contributions of Arema Pereira, MD, Panagiotis Vlagopolous, MD, MS, and Jennifer Buell, PhD, without whom the

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: Because an author of this manuscript is an editor for AJKD, the peer-review and decision-making processes were handled entirely by an Associate Editor (Katherine Tuttle, MD, Sacred Heart Medical Center) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.

: Originally published online as doi:10.1053/j.ajkd.2008.08.022 on December 15, 2008.

View full text

Original InvestigationPathogenesis and Treatment of Kidney DiseaseAlbuminuria, Cognitive Functioning, and White Matter Hyperintensities in Homebound Elders

Background

Study Design

Setting & Participants

Predictor

Outcome

Results

Limitations

Conclusions

Section snippets

Study Population

Results

Discussion

Acknowledgements

Lancet Neurol

J Neurol Sci

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

J Neurol Sci

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Brain infarction and the clinical expression of Alzheimer diseaseThe Nun Study

JAMA

Subcortical cognitive impairment in dialysis patients

Hemodial Int

Cognitive impairment in hemodialysis patients is common

Neurology

Chronic kidney disease and cognitive impairment in the elderly: The Health, Aging, and Body Composition Study

J Am Soc Nephrol

Moderate renal impairment and risk of dementia among older adults: The Cardiovascular Health Cognition Study

J Am Soc Nephrol

Chronic kidney disease is associated with white matter hyperintensity volume: The Northern Manhattan Study (NOMAS)

Stroke

Cystatin C and subclinical brain infarction

J Am Soc Nephrol

Original Investigation
Pathogenesis and Treatment of Kidney Disease
Albuminuria, Cognitive Functioning, and White Matter Hyperintensities in Homebound Elders