Grant: CIHR Fellowship

Late-life depression affects approximately 20% of older adults in Canada, though the rates can be as high as 40% in hospitals. Chronic, or treatment-resistant late-life depression (TRLLD) escalates the risk for both Alzheimer's and vascular dementia by as much as 33%. As Canada's population ages, the increasing number of older adults suffering from dementia represents a massive drain on social and healthcare resources. Lifestyle factors such as exercise, education, challenging jobs and learning a second language are collectively known as cognitive reserve (CR) and extend the amount of time a person can cope with Alzheimer's-related degeneration. Two brain circuits involved in cognitive ability and memory are both decimated by TRLLD and dementia, while CR actively strengthens brain regions involved in these functions. Does having higher CR allow people with TRLLD to recover faster and perhaps avert the conversion to dementia? In the present study, we will assess the impact of CR on cognitive ability and memory in older adults with TRLLD at first visit and across time through the course of novel drug treatments. We predict that higher CR accrued over the lifetime will strengthen brain circuits involved in cognitive ability thus allowing these individuals to better resist the devastating effects of TRLLD. Additionally, novel work from our group shows that patient subgroups can be identified using optimal combinations of brain imaging and behavioral data. These subgroups likely represent more biologically plausible groupings than clinical labels afford. We propose to use this technique to identify subgroups of individuals with TRLLD and varying amounts of CR. People with higher CR should respond to novel treatments faster and have a lower risk of converting to dementia. Conversely, these findings also represent a novel way to identify those individuals most at risk of converting to dementia which will allow for intervention far in advance of cognitive impairment.