Grant: Project Grant

Cardiovascular disease (CVD) is highly prevalent amongst Canadians and represents an important risk factor for late-life cognitive impairment (i.e. learning, memory) and dementia, including Alzheimer's disease. Conditions such as atherosclerosis (ATX) and hypertension (HT) have been linked to arterial stiffness, alterations in cerebral blood flow, and decreased brain perfusion. Initially discovered for its role in blood coagulation, vitamin K (VK) has recently emerged as an important nutrient for vascular health and brain function. In the vasculature, VK is beneficial through the actions of proteins which act as calcium inhibitor. In brain, VK is widely present and participates in the activation of a number of proteins involved in blood flow, vessel integrity, and brain cell activity. Moreover, VK has been shown to modulate cognition in both animals and humans, notably during aging. In studies by our group, feeding rats a high VK diet throughout their lives was associated with better learning and memory functions in late-life. The overreaching goal of this proposal is to provide evidence for the beneficial effect of enhanced VK status on cognition in the context of CVD and characterize its mechanism of action. Our specific aim will be to determine, using two rodent models, the potential of VK to mitigate cognitive impairment through an amelioration of the vasculature, cerebral blood flow, brain oxygenation, and brain structure integrity. Animals will be fed various levels of dietary VK and will be investigated at different life stages. Experiments will include multidisciplinary approaches including imagery studies. The proposed studies will be amongst the very few to integrate state-of-the-art imaging technology to investigate the role of a nutrient in rodent brain, and will expand the importance of VK to the context of CVD. Importantly, they will help plan future intervention studies in this group of patients who could largely benefit from this nutrient.