Mohamad Taha, University of Ottawa
Duncan Stewart, Ottawa Hospital Research Institute
Michael McBurney, Ottawa Hospital Research Institute
Vascular cognitive impairment (VCI) is a spectrum of cognitive disorders with evidence of cognitive impairment affecting at least one cognitive domain. Diabetes mellitus can lead to development VCI, characterized by severe vascular dementia and memory and learning impairments. With diabetes numbers on the rise in Canada, currently estimated to be around 2.7 million cases, it is important that novel therapeutics be developed to target the accompanying cognitive impairment. This project aims to develop a robust model of VCI with diabetes associated with premature vascular aging. The model established will allow further identification of novel biomarkers for risk factors of VCI and testing of new potential therapies for such vascular disorders, both of which are part of the priority areas of research for the vascular network. In addition, this project will provide novel mechanistic insight into the role of Sirtuin 1, a deacetylase that has previously been implicated as a key pathway in response to vascular stress and vascular longevity, in the pathogenesis of vascular cognitive impairment and vascular dementia. This work will also determine whether activation of Sirtuin 1 activity, through increasing the concentration of its co-substrate NAD+ or by using allosteric small molecule activators, might be an effective therapeutic or preventative strategy in VCI.