Vitamin K status and cognitive function in healthy older adults Nancy Presse a, b , Sylvie Belleville a, c , Pierrette Gaudreau d, e , Carol E. Greenwood f , Marie-Jeanne Kergoat a, d , Jose A. Morais g , Hélène Payette h , Bryna Shatenstein a, b , Guylaine Ferland a, b, * a Centre de recherche, Institut Universitaire de Gériatrie de Montréal, Montréal, Quebec, Canada b Département de Nutrition, Université de Montréal, Montréal, Quebec, Canada c Département de Psychologie, Université de Montréal, Montréal, Quebec, Canada d Département de Médecine, Université de Montréal, Montréal, Quebec, Canada e Centre de Recherche, Centre Hospitalier de l’Université de Montréal, Montréal, Quebec, Canada f Kunin Lunenfeld Applied and Evaluative Unit, Baycrest and Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada g McGill Nutrition and Food Science Centre and Department of Medicine, Division of Geriatrics, McGill University Health Centre and School of Dietetics and Human Nutrition, McGill University, Montréal, Quebec, Canada h Centre de recherche sur le vieillissement, Institut Universitaire de Gériatrie de Sherbrooke and Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada article info Article history: Received 19 December 2012 Received in revised form 22 April 2013 Accepted 30 May 2013 Available online 11 July 2013 Keywords: Vitamin K Phylloquinone Cognition Aging abstract Evidence is accumulating that vitamin K could have a role in cognition, especially in aging. Using data from the Québec Longitudinal Study on Nutrition and Successful Aging (NuAge), a cross-sectional analysis was conducted to examine the associations between vitamin K status, measured as serum phylloquinone concentrations, and performance in verbal and non-verbal episodic memory, executive functions, and speed of processing. The sample included 320 men and women aged 70 to 85 years who were free of cognitive impairment. After adjustment for covariates, higher serum phylloquinone con- centration (log-transformed) was associated with better verbal episodic memory performances (F ¼ 2.43, p ¼ 0.048); specifically with the scores (Z-transformed) on the second (b ¼ 0.47; 95% confidence interval [CI] ¼ 0.13e0.82), third (b ¼ 0.41; 95% CI ¼ 0.06e0.75), and 20-minute delayed (b ¼ 0.47; 95% CI ¼ 0.12 e0.82) free recall trials of the RL/RI-16 Free and Cued Recall Task. No associations were found with non- verbal episodic memory, executive functions, and speed of processing. Our study adds evidence to the possible role of vitamin K in cognition during aging, specifically in the consolidation of the memory trace. Ó 2013 Elsevier Inc. All rights reserved. 1. Introduction Vitamin K is a fat-soluble compound found predominantly in green leafy vegetables and, to lesser extent, other vegetables, fruits, and some vegetable oils. It was originally discovered for its role in blood coagulation, activating the vitamin Kedependent clotting factors through its function as a cofactor of the g-glutamyl- carboxylase. The discovery of additional vitamin K-dependent proteins (e.g. osteocalcin) and functions independent of the g- carboxylation has expanded the role of vitamin K beyond coagu- lation (Suttie, 2009). A role in the human brain was first suspected after cases of central nervous system abnormalities in newborns exposed in utero to vitamin K antagonists (Hall et al., 1980). In rat and human brain tissues, high vitamin K levels in the form of menaquinone-4 (MK-4) have been reported (Carrie et al., 2004; Thijssen and Drittij-Reijnders, 1994, 1996). In rodents, brain MK-4 was shown to respond, in a dose-dependent manner, to intakes of vitamin K, whether provided in a natural dietary form (phylloqui- none) or a synthetic form (Carrie et al., 2004; Okano et al., 2008; Thijssen and Drittij-Reijnders, 1994). Our understanding of the vitamin K functions in brain is growing (Ferland, 2012). The vitamin K-dependent proteins Gas6 (growth arrest-specific gene 6) and protein S are expressed in the central nervous system (He et al., 1995; Prieto et al., 1999). Protein S is notably known to possess neuroprotective effects during hypoxic/ ischemic injury, whereas Gas6 is now recognized as an important regulator of cell survival, cell growth, and myelination processes (Ferland, 2012). Furthermore, vitamin K participates in the meta- bolism of sphingolipids, a major constituent of the myelin sheath and neuronal membranes, also involved in important molecular events such as cell signaling (Denisova and Booth, 2005; Ferland, 2012). Finally, the K vitamers were also shown to possess neuro- protective effects against oxidative-induced death of primary * Corresponding author at: Centre de recherche, Institut Universitaire de Gériatrie de Montréal, 4565 Queen Mary, Montréal, Quebec H3W 1W5, Canada. Tel.: þ1 514 340 2800 3236; fax: þ1 514 340 2801. E-mail address: guylaine.ferland@umontreal.ca (G. Ferland). Contents lists available at SciVerse ScienceDirect Neurobiology of Aging journal homepage: www.elsevier.com/locate/neuaging 0197-4580/$ e see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.neurobiolaging.2013.05.031 Neurobiology of Aging 34 (2013) 2777e2783