Serotonergic Function in Dementia

描述(由申请人提供)： 这项研究将启动候选人的职业目标，即通过允许她接受使用5-羟色胺受体特定放射配基的PET成像和统计分析来寻找证据来指导痴呆症患者的神经精神障碍的治疗。多伦多大学为她提供的导师和设施的协同专业知识不能在美国复制用于这项研究。 假设：额颞叶变性(FTLD)患者的焦虑、强迫行为和烦躁不安与额叶和颞叶皮质5HT1a受体密度降低有关。PET成像可以显示和量化这些差异。 具体目标：1)用[11C]Way-100635进行正电子发射计算机断层扫描，量化FTLD受试者与正常、年龄和教育程度匹配的对照组在额叶和颞叶皮质感兴趣区的5HT1A受体结合潜力的差异。2)比较有无情绪症状的FTLD受试者的PET检查结果。如果额叶感兴趣区5-羟色胺能功能的改变与症状相关，本研究将为进一步研究此类患者的5-羟色胺能药物治疗提供基础。

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.