title: Vitamin K Antagonists and Cognitive Function in Older Adults: The Three-City Cohort Study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Département de Nutrition, Faculté de Médecine, Université de Montréal, Quebec, Canada.
authors.forename: Guylaine
authors.initials: G
authors.lastname: Ferland
authors.affiliation: University of Bordeaux and INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France. catherine.feart@isped.u-bordeaux2.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Feart
authors.affiliation: Faculté de Pharmacie, Université de Montréal, Quebec, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Presse
authors.affiliation: University of Bordeaux and INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France. Present address: INSERM CIC1401, Amélie Raba-Léon, Bordeaux, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Lorrain
authors.affiliation: CHU Bordeaux, France. University of Bordeaux, INSERM U657, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Bazin
authors.affiliation: University of Bordeaux and INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France. INSERM, CIC 1401 Bordeaux, Clinical Epidemiology Unit, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Helmer
authors.affiliation: INSERM, U1061, Hôpital La Colombière Montpellier, France. Université Montpellier 1, France. Centre de Mémoire de Ressources et de Recherche Languedoc Roussillon, Hôpital Gui de Chauliac, Montpellier, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Berr
authors.affiliation: Department of Neuroscience, Division of Geriatric Medicine and Memory Clinic, UPRES EA4638, UNAM, Angers University Hospital, France. Robarts Research Institute, The University of Western Ontario, London, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Annweiler
authors.affiliation: Centre Mémoire Ressources et Recherche, CHU Dijon, Bocage Central, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rouaud
authors.affiliation: University of Bordeaux and INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dartigues
authors.affiliation: CHU Bordeaux, France. University of Bordeaux, INSERM U657, France. INSERM, CIC1401, Pharmacoepidemiology Unit, Bordeaux, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Fourrier-Reglat
authors.affiliation: University of Bordeaux and INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Barberger-Gateau
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects; D003072:Cognition Disorders / Q000175:diagnosis*; D005260:Female; D005602:France; D015577:Geriatric Assessment; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D012307:Risk Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D010975:Platelet Aggregation Inhibitors; D014812:Vitamin K
keywords: Aging; Cognitive decline; Cohort; Vitamin K antagonist