Grant: CIHR Fellowship

Mild cognitive impairment (MCI), a brain disorder in which patients have more memory and thinking problems than healthy people their age, often progresses to Alzheimer's disease (AD) where memory abilities and daily tasks are severely impaired. Apathy, characterized by a state of reduced interest, motivation and activity is one of the most common non-memory related symptoms of MCI and AD occurring in about 50%, and 80% of patients, respectively. Furthermore, 60% of MCI patients with apathy progress to AD. Medications which have been studied for the treatment of apathy have shown that only 30% of patients benefit. Understanding the underlying brain changes that occur in patients with apathy may help identify new treatments and delay progression to AD. Apathy has been associated with changes in the frontal cortex; regions at the front of the brain. In patients with memory difficulties, changes in the frontal cortex have been associated with a build-up of AD-related harmful proteins such as tau. Tau is considered a primary biomarker of AD, and is linked to cell death in the brain. However the relationship between apathy and tau is unclear. Fortunately, tau can be measured easily using positron emission tomography, an imaging test that uses a radioactive molecule to detect disease before it shows up on other imaging tests. Understanding the relationship between apathy and tau would help identify which patients can be targeted for early treatment that may delay or prevent progression to AD, and may also identify a new treatment to improve apathy and AD. Specifically, drugs that target tau may be of interest. Therefore, I propose to study differences in tau accumulation in the frontal cortex between cognitively impaired (MCI or AD) individuals with and without apathy, and whether other important characteristics such as size of brain region, presence of other behavioural symptoms, and severity of memory difficulties, affect the severity of tau accumulation.