Grant: Project Grant

Cardiovascular disease (CVD) is highly prevalent amongst Canadians and represents an important risk factor for late-life cognitive dysfunction (i.e. learning, memory) and dementia. Conditions such as atherosclerosis (ATX) and hypertension (HT) have been linked to early brain aging and impairment. Historically discovered for its role in blood coagulation, vitamin K (VK) contributes to vascular health and cognition through the action of proteins involved in anti-calcification, vascular and brain cell survival, and anti-inflammatory process. Over the years, our group has provided significant evidence for the role of VK nutritional status in learning abilities and memory, in both rodents and humans. In a mouse model of induced arterial stiffness, we recently showed that an enriched VK diet modulates vascular calcification and inflammation, improves vascular reactivity, brain oxygenation, and cognition. In this proposal, we will expand our investigation of the VK actions in the more complex condition of ATX, which affects a growing number of Canadians. Our specific aim will be to determine, in a mouse model of ATX, the potential of VK to mitigate cognitive impairment through an amelioration of the vasculature, cerebral blood flow, and brain structure integrity. We will also investigate the potential negative impact of statins in the actions of VK as this drug family interferes with VK metabolism. Male and female mice will be fed various levels of dietary VK and will be investigated at adulthood and middle-age. Sub-groups of mice will be treated with statins. Experiments will include multidisciplinary methodological approaches (e.g. behavior, imagery, biochemistry). The proposed experiments will be the first to investigate the impact of VK status on cognition in the context of ATX. Importantly, they will help plan future intervention studies in this group of patients who could largely benefit from this nutrient.