{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:39:53Z","timestamp":1790617193777,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,5,24]],"date-time":"2018-05-24T00:00:00Z","timestamp":1527120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin K participates in brain physiology. This study aimed to determine whether using vitamin K antagonists (VKAs), which interfere with the vitamin K cycle, were (i) cross-sectionally associated with altered cognitive performance, and (ii) independent predictors of cognitive changes in older adults over 24 months. Information was collected on the use of VKAs (i.e., warfarin, acenocoumarol, and fluindione) among 378 geriatric outpatients (mean, 82.3 \u00b1 5.6 years; 60.1% female). Global cognitive performance and executive functions were assessed with Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores, respectively, at baseline and after 12 and 24 months of follow-up. Age, gender, body mass index, mean arterial pressure, disability, gait speed, comorbidities, atrial fibrillation, stroke, carotid artery stenosis, leukoaraiosis grade on computed tomography (CT) scan, psychoactive drugs, antidementia drugs, blood-thinning drugs (i.e., anticoagulants other than VKAs, antiplatelet medications), serum creatinine levels, and vitamin B12 concentrations were considered as potential confounders. Using VKAs was associated with lower (i.e., worse) FAB score at baseline (adjusted \u03b2 = \u22122.1, p = 0.026), and with a decrease in FAB score after 24 months (adjusted \u03b2 = \u2212203.6%, p = 0.010), but not after 12 months (p = 0.659). Using VKAs was not associated with any change in MMSE score at baseline (p = 0.655), after 12 months (p = 0.603), or after 24 months (p = 0.201). In conclusion, we found more severe executive dysfunction at baseline and incident executive decline over 24 months among geriatric patients using VKAs, when compared with their counterparts.<\/jats:p>","DOI":"10.3390\/nu10060666","type":"journal-article","created":{"date-parts":[[2018,5,24]],"date-time":"2018-05-24T07:54:01Z","timestamp":1527148441000},"page":"666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Vitamin K Antagonists and Cognitive Decline in Older Adults: A 24-Month Follow-Up"],"prefix":"10.3390","volume":"10","author":[{"given":"Antoine","family":"Brangier","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine, University Memory Clinic; Research Center on Autonomy and Longevity (CeRAL), University Hospital, F-49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guylaine","family":"Ferland","sequence":"additional","affiliation":[{"name":"Centre de Recherche, Institut Universitaire de G\u00e9riatrie de Montr\u00e9al, Montr\u00e9al, QC H3W 1W5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Rolland","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Institut du Vieillissement, University Hospital, INSERM-U1027, F-31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gautier","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, University Memory Clinic; Research Center on Autonomy and Longevity (CeRAL), University Hospital, F-49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"F\u00e9art","sequence":"additional","affiliation":[{"name":"Institut de Sant\u00e9 Publique, d\u2019\u00c9pid\u00e9miologie et de D\u00e9veloppement ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Universit\u00e9 Bordeaux, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-8109","authenticated-orcid":false,"given":"Cedric","family":"Annweiler","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, University Memory Clinic; Research Center on Autonomy and Longevity (CeRAL), University Hospital, F-49933 Angers, France"},{"name":"Health Faculty and UPRES EA4638, University of Angers, F-49100 Angers, France"},{"name":"Robarts Research Institute, The University of Western Ontario, London, ON N6A 5B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160S","DOI":"10.1378\/chest.08-0670","article-title":"Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines","volume":"133","author":"Ansell","year":"2008","journal-title":"Chest"},{"key":"ref_2","unstructured":"French National Security Agency of Medicines and Health Products (ANSM) (2018, March 21). Anticoagulants in France in 2012: Inventory and Monitoring. Available online: http:\/\/ansm.sante.fr\/var\/ansm_site\/storage\/original\/application\/901e9c291a545dff52c0b41365c0d6e2.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/biof.1004","article-title":"Vitamin K, an emerging nutrient in brain function","volume":"38","author":"Ferland","year":"2012","journal-title":"Biofactors"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3945\/an.111.001784","article-title":"Vitamin K and the nervous system: An overview of its actions","volume":"3","author":"Ferland","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/j.jada.2008.09.013","article-title":"Low vitamin K intakes in community-dwelling elders at an early stage of Alzheimer\u2019s disease","volume":"108","author":"Presse","year":"2008","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/0002-9343(80)90181-3","article-title":"Maternal and fetal sequelae of anticoagulation during pregnancy","volume":"68","author":"Hall","year":"1980","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1111\/jgs.13682","article-title":"Use of Vitamin K Antagonists and Brain Volumetry in Older Adults: Preliminary Results From the GAIT Study","volume":"63","author":"Annweiler","year":"2015","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/gerona\/glu133","article-title":"Vitamin K antagonists and cognitive impairment: Results from a cross-sectional pilot study among geriatric patients","volume":"70","author":"Annweiler","year":"2015","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Beauchet, O., Launay, C.P., Allali, G., Watfa, G., Gallouj, K., Herrmann, F.R., and Annweiler, C. (2013). Anti-dementia drugs and changes in gait: A pre-post quasi-experimental pilot study. BMC Neurol., 13.","DOI":"10.1186\/1471-2377-13-184"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vannier-Nitenberg, C., Dauphinot, V., Bongue, B., Sass, C., Rouch, I., Beauchet, O., Krolak-Salmon, P., and Fantino, B. (2013). Early detection of memory impairment in people over 65 years old consulting at Health Examination Centers for the French health insurance: The EVATEM protocol. BMC Geriatr., 13.","DOI":"10.1186\/1471-2318-13-55"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"Mini-mental state: A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1212\/WNL.55.11.1621","article-title":"The FAB: A frontal assessment battery at bedside","volume":"55","author":"Dubois","year":"2000","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1161\/01.CIR.0000154900.76284.F6","article-title":"Recommendations for blood pressure measurment in humans and experimental animals: Part 1: Blood pressure measurement in humans: A statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research","volume":"111","author":"Pickering","year":"2005","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1212\/01.wnl.0000228228.70065.f1","article-title":"Restriction in complex activities of daily living in MCI: Impact on outcome","volume":"67","author":"Chrysostome","year":"2006","journal-title":"Neurology"},{"key":"ref_15","first-page":"541","article-title":"Experience from a multicentre stroke register: A preliminary report","volume":"54","author":"Hatano","year":"1976","journal-title":"Bull. World Health Organ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1161\/01.STR.32.6.1318","article-title":"A new rating scale for age-related white matter changes applicable to MRI and CT","volume":"32","author":"Wahlund","year":"2001","journal-title":"Stroke"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tamadon-Nejad, S. (2018, March 21). Warfarin-Induced Vitamin K Deficiency Is Associated with Cognitive and Behavioral Perturbations, and Alterations in Brain Sphingolipids in Rats. Available online: https:\/\/papyrus.bib.umontreal.ca\/xmlui\/handle\/1866\/10871.","DOI":"10.3389\/fnagi.2018.00213"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1111\/j.1538-7836.2004.00993.x","article-title":"Dementia in subjects with atrial fibrillation: Hemostatic function and the role of anticoagulation","volume":"2","author":"Barber","year":"2004","journal-title":"J. Thromb. Haemost."},{"key":"ref_19","first-page":"269","article-title":"Is there any evidence for a protective effect of antithrombotic medication on cognitive function in men at risk of cardiovascular disease? Some preliminary findings. J. Neurol. Neurosurg","volume":"62","author":"Richards","year":"1997","journal-title":"Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"338","DOI":"10.7326\/0003-4819-158-5-201303050-00007","article-title":"Cognitive impairment associated with atrial fibrillation. A meta-analysis","volume":"158","author":"Kalantarian","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1079\/BJN19940043","article-title":"Vitamin K distribution in rat tissues: Dietary phylloquinone is a source of tissue menaquinone-4","volume":"72","author":"Thijssen","year":"1994","journal-title":"Br. J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/S0028-3908(02)00333-7","article-title":"Gas6 rescues cortical neurons from amyloid beta protein-induced apoptosis","volume":"43","author":"Yagami","year":"2002","journal-title":"Neuropharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1161\/01.CIR.0000058460.34453.5A","article-title":"Protein S confers neuronal protection during ischemic\/hypoxic injury in mice","volume":"107","author":"Liu","year":"2003","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/S0022-2275(20)38426-1","article-title":"Warfarin administration reduces synthesis of sulfatides and other sphingolipids in mouse brain","volume":"29","author":"Sundaram","year":"1988","journal-title":"J. Lipid Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119S","DOI":"10.1016\/S0035-3787(08)73302-2","article-title":"Frontal lobe, executive functions and cognitive control","volume":"164","author":"Godefroy","year":"2008","journal-title":"Rev. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2515\/therapie\/2009021","article-title":"Relevance of the evaluation criteria used in clinical trials for Alzheimer\u2019s disease","volume":"64","author":"Truffinet","year":"2009","journal-title":"Therapie"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dinomais, M., Celle, S., Duval, G.T., Roche, F., Henni, S., Bartha, R., Beauchet, O., and Annweiler, C. (2016). Anatomic Correlation of the Mini-Mental State Examination: A Voxel-Based Morphometric Study in Older Adults. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162889"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-1-60761-803-4_5","article-title":"Novel anticoagulant therapy: Principle and practice","volume":"663","author":"Mousa","year":"2010","journal-title":"Methods Mol. Biol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/6\/666\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:05:43Z","timestamp":1760195143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/6\/666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,24]]},"references-count":28,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,6]]}},"alternative-id":["nu10060666"],"URL":"https:\/\/doi.org\/10.3390\/nu10060666","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,24]]}}}