Albuminuria and decline in cognitive function: The ONTARGET/TRANSCEND studies

Arch Intern Med. 2011 Jan 24;171(2):142-50. doi: 10.1001/archinternmed.2010.502.


Background: Microvascular disease of the kidney (manifesting as albuminuria) and of the brain (manifesting as cognitive decline) may share a common pathogenesis. Gaining an understanding of the concomitant history of these 2 conditions may inform clinical practice and lead to novel prevention and treatment approaches.

Methods: A total of 28 384 participants with vascular disease or diabetes mellitus were examined. At baseline and year 5, participants underwent a Mini-Mental State Examination (MMSE) and urine testing for albumin excretion. Multivariable logistic regression was used to determine the association between albumin excretion and MMSE score, cross-sectionally and prospectively, and whether angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker use modified the association.

Results: Compared with participants with normoalbuminuria, those with microalbuminuria (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.11-1.44]) and macroalbuminuria (1.49; 1.20-1.85) were more likely to have a reduced MMSE score (<24). On follow-up, participants with baseline albuminuria had increased odds of cognitive decline (decrease in MMSE score ≥3 points) compared with those with normoalbuminuria (microalbuminuria: OR, 1.22; 95% CI, 1.07-1.38; macroalbuminuria: 1.21; 0.94-1.55). Participants who developed new albuminuria had increased odds of cognitive decline during follow-up compared with those who remained normoalbuminuric (new microalbuminuria: OR, 1.30; 95% CI, 1.12-1.52; new macroalbuminuria: 1.77; 1.24-2.54). Participants with baseline macroalbuminuria treated with an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker had lower odds of MMSE decline than participants treated with placebo.

Conclusion: Factors that contribute to albuminuria may contribute to cognitive decline, supporting the notion that both conditions share a common microvascular pathogenesis. Trial Registration Identifier: NCT00153101.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / complications*
  • Albuminuria / drug therapy*
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Cognition Disorders / etiology*
  • Cognition Disorders / prevention & control*
  • Cohort Studies
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / epidemiology
  • Diabetic Nephropathies / complications
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Risk Factors


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors

Associated data