Grant: CIHR Fellowship

Background: Approximately one third of patients develop cognitive impairment following acute stroke. Post-stroke dementia increases disability and triples the risk of death. One cause of stroke is disease in the small blood vessels. Small vessel disease (SVD) is very common in the elderly, even in the absence of stroke, and instead can cause a mini-stroke or transient ischemic attack (TIA), or lead to damage in the white matter of the brain. SVD is an important contributor to cognitive decline and dementia in the elderly. However, the physical processes underlying this relationship remain poorly understood. One potential factor is lack of clearance of 'amyloid', a toxic protein that accumulates with age and can build up in small blood vessels. Hence, elderly individuals with SVD may be at increased risk of amyloid build-up compared to healthy individuals. Objectives: The proposed study will 1) use a new brain imaging technique called amyloid positron emission tomography (PET) to measure amyloid in patients with SVD compared to healthy individuals, 2) determine if increased amyloid relates to cognitive impairment, and 3) determine if cognitive function decreases more over time in individuals with higher amyloid levels. Methods: Patients with SVD involving moderate to severe white matter damage and TIA will be recruited. Participants will undergo magnetic resonance imaging to quantify white matter disease and amyloid PET imaging to measure brain amyloid. They will also undergo a series of cognitive tests. All testing will be repeated at 1 year to assess changes in amyloid levels and cognitive function. Significance: The proposed study will be the first to use amyloid PET imaging to investigate the connections between SVD and cognitive decline. This research will address an important gap in our knowledge about the development of dementia in SVD, with the goal of preventing progression to dementia, which has a devastating effect on health and quality of life.