Serum uric acid and subsequent cognitive performance in patients with pre-existing cardiovascular disease

PLoS One. 2015 Mar 20;10(3):e0120862. doi: 10.1371/journal.pone.0120862. eCollection 2015.


High serum uric acid (UA) levels are associated with numerous vascular risk factors, and vascular disease, that predispose patients to cognitive impairment, yet UA is also a major natural antioxidant and higher levels have been linked to slower progression of several neurodegenerative disease. In-order to test the association between UA and subsequent cognitive performance among patients that carry a high vascular burden, UA levels were determined by calorimetric enzymatic tests in a sub-cohort of patients with chronic cardiovascular disease who previously participating in a secondary prevention trial. After an average of 9.8±1.7 years, we assessed cognitive performance (Neurotrax Computerized Cognitive Battery) as well as cerebrovascular reactivity (CVR) and common carotid intima-media thickness (IMT). Among 446 men (mean age 62.3±6.4 yrs) mean UA levels were 5.8±1.1 mg/dL. Adjusted linear regression models revealed that low UA levels (bottom quintile) were associated with poorer cognitive performance. Adjusted differences between the bottom quintile and grouped top UA quintiles were (B coefficient±SE) -4.23±1.28 for global cognitive scores (p = 0.001), -4.69±1.81 for memory scores (p = 0.010), -3.32±1.43 for executive scores (p = 0.020) and -3.43±1.97 for visual spatial scores (p = 0.082). Significant difference was also found for attention scores (p = 0.015). Additional adjustment for impaired CVR and high common carotid IMT slightly attenuated the relationship. Stronger UA effect on cognitive performance was found for older (age>65) patients with significant age interaction for global cognitive score (p = 0.016) and for executive (p = 0.018) and attention domains (p<0.001). In conclusion, we demonstrate that low UA levels in patients with preexisting cardiovascular disease are associated with poorer cognitive function a decade later. These findings lend support to the hypothesis that oxidative stress may be involved in the pathogenesis of age-associated cognitive impairment.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / psychology*
  • Cerebrovascular Disorders / blood
  • Cerebrovascular Disorders / diagnosis
  • Cerebrovascular Disorders / psychology
  • Cognition Disorders / blood*
  • Female
  • Humans
  • Male
  • Memory
  • Middle Aged
  • Psychomotor Performance
  • Uric Acid / blood*


  • Uric Acid

Grant support

This study was supported by a grant from the Chief Scientist Office, Israeli Ministry of Health and by a grant from the Leslie and Susan Gonda Foundation, Los Angeles, California. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.