Grant: Doctoral Research Award: Canada Graduate Scholarships

Dementia ranks among the top ten causes of mortality in Canada. Dementia can be described as a syndrome that leads to progressive loss of cognitive functions and independence. The presence of an underlying neurodegenerative disease, or often multiple neurodegenerative diseases in combination, is the major cause of the dementia syndrome. These multiple dementia-causing pathologies often co-exist to varying degrees as "mixed" disease, leading to overlap in clinical symptoms and variability in disease progression. Therefore, to address this variability and identify risks that are shared across neurodegenerative dementias, it is desirable to move away from the traditional approach of analyzing neurodegenerative disorders as discrete entities, but rather studying them as a group of related disorders along the dementia spectrum. In my research proposal, I will harmonize large, well-characterized, multimodal datasets consisting of "real world" patients representing the full spectrum of neurodegenerative dementias. I will evaluate how genomic and non-genomic (such as, age, education, sex, and cardiovascular) risk factors impact neuroimaging, blood/plasma, and cognitive/behavioural measures in a disease-agnostic fashion (that is, blinded to clinical diagnosis). More specifically, I will first identify robust genotype-phenotype and polygenic risk-phenotype relationships (endophenotypes), and then recategorize all patients into dementia "biotypes" using data-driven machine learning approaches irrespective of the clinical diagnostic categories. Neuropathological data will be assessed to investigate how the post-mortem relationships compare with antemortem relationships. I will also consider factors that may influence my results such as, sex, cardiovascular and lifestyle factors, and education. With this investigation, I hope to advance Canada's national strategy to reduce the burden of dementia through early detection and the application of precision medicine approaches.