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Evaluating the Presymptomatic Time Window in Genetic Frontotemporal Dementia
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Evaluating the Presymptomatic Time Window in Genetic Frontotemporal Dementia
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Dissertation
Evaluating the Presymptomatic Time Window in Genetic Frontotemporal Dementia
2020
Overview
Frontotemporal Dementia (FTD) is the second most common form of dementia in those under 65 years of age. To date the only known risk factors are genetic, and a third of FTD is inherited. Unique to the study of genetic FTD is examining of those at-risk of FTD who are many years from expected symptom onset. As the era of clinical trials for genetic FTD approaches, it is clear that pharmaceutical companies aim to target therapeutic interventions many years before symptom onset. To date one of the greatest challenges in genetic FTD is understanding the age at which at-risk individuals are likely to develop symptoms and having sensitive biomarkers to detect early presymptomatic changes. The work outlined in this thesis investigated the presymptomatic phase of genetic FTD, focusing on improving our understanding of when individuals at-risk of FTD are likely to develop symptoms; and exploring well-validated and novel cognitive assessments to devise more sensitive measures of cognition in genetic FTD. I begin my thesis by performing a retrospective study of genetic FTD to understand the factors that influence age at symptom onset, showing that an individual’s age at onset is significantly correlated with both parental and mean family age at onset. In the subsequent chapters I build upon these findings to explore cognitive changes in genetic FTD. I devise a cognitive composite based on pre-existing neuropsychology assessments to provide the optimal combination of assessments for use in a potential clinical trial. I also devised a novel cognitive assessment tool for the detection of early presymptomatic cognitive changes in genetic FTD to provide a proof of concept that this novel technique is sensitive to early presymptomatic cognitive changes. The work expands on what is currently known about the presymptomatic phase of genetic FTD and provides new avenues for understanding early cognitive changes.
Publisher
ProQuest Dissertations & Theses
Subject
