循环叶绿醌浓度与多种认知测量指标呈正相关，但脑甲萘醌-4 无此相关性：百岁老人的探索性发现。

Concentrations of Circulating Phylloquinone, but Not Cerebral Menaquinone-4, Are Positively Correlated with a Wide Range of Cognitive Measures: Exploratory Findings in Centenarians.

机构信息

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

Gerald J and Dorothy R Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.

出版信息

J Nutr. 2020 Jan 1;150(1):82-90. doi: 10.1093/jn/nxz200.

DOI:10.1093/jn/nxz200

PMID:31504672

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.

摘要

背景

维生素 K（VK）以叶绿醌（PK）和甲萘醌（MKs）的形式存在。VK 对老年人认知健康的作用正在显现，但关于人类大脑中 VK 的摄取和代谢的证据有限。

目的

本研究的主要目的是描述认知功能不同的老年人群的大脑中 VK 的分布情况。此外，还研究了循环中的 VK 浓度（VK 摄入的生物标志物）与大脑中 VK 浓度和认知之间的关系。

方法

从参加佐治亚州百岁老人研究的 48 名死者（年龄 98-107 岁；25 名痴呆，23 名非痴呆）中获得血清或血浆（n=27）和额皮质（FC；n=46）和颞皮质（TC；n=33）的脑样本。使用 HPLC 结合荧光检测法测量循环和脑 VK 浓度。在死亡前 1 年内进行认知评估。进行了血清/血浆或脑 VK 浓度与认知功能之间的偏相关分析，调整了协变量，并按痴呆和抗血栓形成药物的使用进行了分离。

结果

MK-4 是 FC（平均±SD=4.92±2.31 pmol/g，≥89.15%±5.09%的总 VK）和 TC（4.60±2.11 pmol/g，≥89.71%±4.43%的总 VK）中均占主导地位的维生素 K 同型物，无论认知状态如何。抗血栓形成药物使用者的 FC（P<0.05）和 TC（P<0.001）中的 MK-4 浓度分别低 34.0%和 53.9%。循环 PK 与脑 MK-4 或总 VK 浓度无相关性。在认知正常的百岁老人中，循环 PK 浓度与广泛的认知测量指标显著相关（P<0.05）。相比之下，脑 MK-4 浓度与认知表现无关，无论是否排除抗血栓形成药物使用者。