Modelling the heterogeneity of brain aging and dementia risk - integrating brain structural and functional changes

Alzheimer's disease (AD) becomes more common as the brain ages, but not everyone is affected equally. Understanding why brain aging is slower in some people than in others, and why some people can even improve, would offer a major advance for successful risk factor control and dementia prevention. Even seemingly small changes in bio-markers and vascular risk factors can accumulate to affect memory and thinking. Current methods require such changes to being fairly big, and to go mostly in one direction, i.e. getting worse. Our method allows many small changes to be combined. Likewise, we developed a measure that combines Brain Atrophy and Lesions in a single Index (BALI). We also developed a new analytical method, which takes into account that small improvements are also often seen. Together, the new methods allow us to precisely model the dynamics of brain aging: not just decline, but also stability and improvement, and link it with risk and protective factors. This CIHR grant provides a perfect opportunity to develop this important research. We will extend these novel studies to validate and generalize the methods using different neuroimaging databases, including both large multi-site consortia databases and existing local datasets. We will link brain MRI data with data on biomarkers, brain function, and with clinical and lifestyle assessments. In this way, we will look at the relative contributions of brain structural changes on brain function in both men and women. The research will allow us to study how the heterogeneity in brain structure and function evolve. Results of these analyses will benefit a better understanding of brain aging that can potentially lead to the slowing of it and the prevention of dementia. This research will be conducted collaboratively in two established neuroimaging centers in Halifax and in Toronto and will involve first line knowledge users, to promote knowledge translation and clinical application.