Vitamin K Antagonists and Cognitive Function in Older Adults: The Three-City Cohort Study

J Gerontol A Biol Sci Med Sci. 2016 Oct;71(10):1356-62. doi: 10.1093/gerona/glv208. Epub 2015 Nov 17.


Background: A growing body of evidence supports a beneficial role for vitamin K in brain and cognition, notably in studies where animals are rendered vitamin K deficient by warfarin, a potent vitamin K antagonist (VKA). Given VKAs are commonly used oral anticoagulants in older persons, we investigated the relationship between VKA therapy and cognitive performances over 10 years in participants of the Three-City study.

Methods: The Three-City cohort included 7,133 nondemented community dwellers, aged 65 years or older at baseline. Exposures to VKAs and platelet aggregation inhibitors, another antithrombotic agent, were determined at baseline. Participants underwent cognitive assessment at baseline and every 2 years over 10 years. Associations were analyzed with mixed linear models adjusting for many covariates including VKA and platelet aggregation inhibitor indications.

Results: About 239 (3.4%) and 1,192 (16.7%) of the participants were treated with VKAs and platelet aggregation inhibitors at baseline, respectively. VKA treatment was significantly associated with worse performances on Benton Visual Retention Test assessing visual memory (adjusted mean difference -0.29; p = .02 in multivariate models) and Isaacs Set Test assessing verbal fluency (adjusted mean difference -1.37; p = .0009) at baseline. Treatment with VKAs was not associated with global cognitive functioning on the Mini Mental State Examination, neither with rate of subsequent decline in scores on all three cognitive tests. No associations were found between platelet aggregation inhibitors and cognitive performances or rate of decline.

Conclusion: These findings do not indicate a long-term detrimental effect of VKAs on cognition, but the risk-benefit balance of VKA treatment still deserves further research.

Keywords: Aging; Cognitive decline; Cohort; Vitamin K antagonist.

Publication types

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

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Antithrombins / administration & dosage*
  • Antithrombins / adverse effects
  • Cognition Disorders / diagnosis*
  • Female
  • France
  • Geriatric Assessment
  • Humans
  • Longitudinal Studies
  • Male
  • Neuropsychological Tests
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Prospective Studies
  • Risk Factors
  • Vitamin K / antagonists & inhibitors*


  • Anticoagulants
  • Antithrombins
  • Platelet Aggregation Inhibitors
  • Vitamin K

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