Grant: CIHR REDI Early Career Transition Award - Brain Health and Cognitive Impairment

Dementia is a growing concern as the global population ages, but medications aimed at stopping or reversing dementia have failed. Therefore, interventions are now focusing on treating individuals at risk of cognitive problems and developing dementia, such as those with heart disease and diabetes. This project aims to improve cognitive outcomes and reduce dementia risk in individuals with heart disease and diabetes in two phases. In phase 1, we will study a new treatment that will boost the benefits of exercise for cognition. Exercise generates biological molecules that regulate metabolism and improve cognition in healthy people. However, these benefits vary in people with heart disease and diabetes. Soluble epoxide hydrolase (sEH) is involved in the metabolism of these molecules to toxic molecules, and individuals with heart disease and diabetes have higher sEH levels than healthy people. This study will confirm the safety of an sEH inhibitor and test how effective it is in improving cognitive outcomes in individuals with heart disease and/or diabetes. We will also determine a biosignature (a combination of markers) in individuals who do and do not respond to treatment to identify those at risk of cognitive impairment and dementia. These findings will be used to design a study based on the profile of biomarkers of individuals with heart disease and diabetes for phase 2 of the study. Individuals will be randomized to continue their care with their family doctor, or assigned to a personalized therapy based on their biosignature. We will also use Ontario healthcare data, to identify separate groups of co-occurring cardiovascular risk factors (CVRFs) - which are risk factors of the heart and blood vessels. The risk of dementia within each group will be determined. These findings will be translated to clinical practice where we will identify individuals at the highest risk of dementia based on their CVRFs, and initiate dementia prevention strategies to reduce that risk.