Concentrations of circulating phylloquinone, but not cerebral menaquinone-4, are positively correlated with a wide range of cognitive measures: exploratory findings in centenarians

Authors: TANPRASERTSUK, JIRAYU - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FERLAND, GUYLAINE - University Of Montreal; JOHNSON, MARY ANN - University Of Nebraska; POON, LEONARD - University Of Georgia; SCOTT, TAMMY - Tufts University; BARBEY, ARON - University Of Illinois; BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WANG, XIANG-DONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; JOHNSON, ELIZABETH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/25/2019
Publication Date: 8/28/2019
Citation: Tanprasertsuk, J., Ferland, G., Johnson, M., Poon, L., Scott, T.M., Barbey, A.K., Barger, K.K., Wang, X., Johnson, E. 2019. Concentrations of circulating phylloquinone, but not cerebral menaquinone-4, are positively correlated with a wide range of cognitive measures: exploratory findings in centenarians. Journal of Nutrition. 150(1): 82-90. https://doi.org/10.1093/jn/nxz200.
DOI: https://doi.org/10.1093/jn/nxz200

Interpretive Summary: Roles of Vitamin K (VK) on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain. In the present study, we characterized VK forms (phylloquinone (PK) and menaquinone-4 (MK-4)) and their distribution in the frontal cortex and the temporal cortex in a cohort of older adults whose cognitive status ranged from intact cognition to severe dementia. We found that MK-4 was the predominant VK in both frontal cortex (>89% of total VK) and temporal cortex (>90% of total VK) in both demented and nondemented subjects, but cerebral MK-4 concentrations were not associated with cognitive performance. We also demonstrated that circulating PK concentrations were positively related to a wide range of cognitive tests among nondemented older adults. The present study provided evidence that circulating VK concentrations may reflect intake of VK-rich foods, but are not related to cerebral MK-4 concentrations in older adults. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function.

Technical Abstract: Background: Vitamin K (VK) exists in the form of phylloquinone (PK) and menaquinones (MKs). Roles of VK on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain. Objectives: The primary objective of this study was to characterize VK distribution in brains of an elderly population with varied cognitive function. In addition, associations among circulating (a biomarker of VK intake) and cerebral VK concentrations and cognition were investigated. Methods: Serum or plasma (n=27) and brain samples from the frontal cortex (FC; n=46) and the temporal cortex (TC; n=33) were acquired from 48 decedents (aged 98-107 y; 25 demented and 23 nondemented) enrolled in the Georgia Centenarian Study. Both circulating and brain VK concentrations were measured using HPLC with fluorescence detection. Cognitive assessment was performed within 1 y prior to mortality. Partial correlations between serum/plasma or cerebral VK concentrations and cognitive function were performed, adjusting for covariates and separating by dementia and antithrombotic use. Results: MK-4 was the predominant vitamer in both FC (mean +/- SD = 4.92 +/- 2.31 pmol/g, >=89.15% +/- 5.09% of total VK) and TC (4.60 +/- 2.11 pmol/g, >=89.71% +/- 4.43% of total VK) regardless of cognitive status. Antithrombotic users had 34.0% and 53.9% lower MK-4 concentrations in FC (P < 0.05) and TC (P < 0.001), respectively. Circulating PK was not correlated with cerebral MK-4 or total VK concentrations. Circulating PK concentrations were significantly associated with a wide range of cognitive measures in nondemented centenarians (P < 0.05). In contrast, cerebral MK-4 concentrations were not associated with cognitive performance, either before or after exclusion of antithrombotic users. Conclusions: Circulating VK concentrations are not related to cerebral MK-4 concentrations in centenarians. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function. Circulating PK may reflect intake of VK-rich foods containing other dietary components beneficial to cognitive health. Further investigation of VK uptake and metabolism in the brain is warranted.