Grant: Master's Award: Canada Graduate Scholarships

Frontotemporal Dementia (FTD) has a strong genetic predisposition. One-third of people who develop FTD have a family history of the disease. Most of which are caused by heritable mutations within the DNA in one of three genes: chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT). Among patients with FTD, sleep problems are prevalent, with up to three-quarters of FTD patients having some sort of sleep problem. Findings have suggested that people with MAPT mutations have more sleep problems than other mutation carriers, but why this occurs remains unclear. The hypothalamus, a brain structure important for regulating sleep, may be the cause of the observed increased sleep problems. The hypothalamus is involved in sleep problems in other neurodegenerative disorders, and FTD patients with MAPT mutations have more pronounced cell death, called atrophy, in the hypothalamus. Few studies have looked at atrophy in the hypothalamus in genetic FTD, and none have related changes in the hypothalamus to increased sleep problems. The question remains, does this atrophy contribute to sleep problems?To address this question, we will use magnetic resonance imaging (MRI), a technology that allows for the detailed imaging of tissue, to scan the brains of people with mutations that cause FTD. We will examine the trajectory of change in the hypothalamus across the lifespan. Using clinical information from these subjects, we will relate changes in hypothalamic structure to the presence and severity of sleep problems. The findings from this project will shed light on the mechanisms that may be at the heart of sleep problems that are common in genetic FTD and may further inform novel treatments for sleep problems in these disorders.