Serotonergic Function in Dementia

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DESCRIPTION (provided by applicant): This study will initiate the candidate's career goal of finding evidence to guide management of neuropsychiatric disturbances in dementia by allowing her training in PET imaging with a serotonin receptor-specific radioligand and statistical analysis. The synergistic expertise of the mentors and facilities available to her at the University of Toronto cannot be reproduced in the US for this study. HYPOTHESIS: Anxiety, obsessive-compulsive behaviors and dysphoria in frontotemporal lobar degeneration (FTLD) are associated with a diminution in 5HT1A receptor density in frontal and temporal cortex. PET imaging can demonstrate and quantify these differences. SPECIFIC AIMS: 1) Quantify the difference in binding potential at 5HT1A receptors as derived from PET imaging with [11C]WAY-100635 in frontal and temporal cortical regions of interest between FTLD subjects and normal, age- and education-matched controls. 2) Compare the same PET findings between FTLD subjects with and without the mood symptoms. If changes in serotonergic function in frontal regions of interest correlate with the symptoms, this study will provide the basis for further investigations to identify serotonergic pharmacotherapy for such patients.