Investigation of the dopamine system in frontotemporal dementia

额颞叶痴呆中多巴胺系统的研究

基本信息

批准号：
7797116
负责人：
Edward D Huey
金额：
$ 24.9万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7797116
关键词：
Adverse effects Adverse event Affect Alleles Amendment Animals Anterior Aphasia Applications Grants Area Atrophic Autopsy Award Beds Behavioral Behavioral Symptoms Bilateral Biological Blood Tests Brain Brain Diseases Brain imaging Caregivers Catechols Categories Cerebrospinal Fluid Cessation of life Chemicals Chemistry Clinical Cognition Cognitive Cognitive deficits Complete Blood Count Complex Comprehension Consult Country Cross-Over Studies Data Dementia Diagnosis Disease Disease Progression Dopamine Double-Blind Method Dyskinetic syndrome Effectiveness Eligibility Determination Enrollment Ensure Enzymes Evaluation Event Exclusion Criteria Experimental Designs Family Family Caregiver Fingers Frontotemporal Dementia Functional Magnetic Resonance Imaging Genetic Genetic Polymorphism Genetic Structures Genotype Goals Grant Grant Review Health system Healthcare Systems Hepatotoxicity Hospitals Image Impairment Incidence Internal Medicine Intervention Investigation Judgment Laboratories Language Language Tests Lead Life Liver Liver Function Tests Lobe Magnetic Resonance Imaging Memory Disorders Methods Minor Monitor Morbidity - disease rate Names National Institute of Neurological Disorders and Stroke Neurobehavioral Manifestations Neuropsychological Tests Neurotransmitters New York Outcome Outpatients Participant Patients Performance Persons Pharmaceutical Preparations Physicians Placebo Control Placebos Plastics Prefrontal Cortex Procedures Process Productivity Progressive Supranuclear Palsy Protocols documentation Psychotic Disorders Reading Recommendation Recording of previous events Reporting Research Research Design Research Ethics Committees Research Personnel Research Project Grants Role Safety Semantic Dementias Serious Adverse Event Services Severities Site Social Behavior Social Functioning Societies Specific qualifier value Speech Symptoms Syndrome System Temporal Lobe Testing Therapeutic Intervention Time Transferase Transferase Gene Ultrasonography United States United States National Institutes of Health Wisconsin Work abnormal involuntary movement base behavior measurement blood oxygen level dependent design disability dopamine system follow-up follower of religion Jewish frontal lobe function improved inhibitor/antagonist innovation meetings member mortality north shore long island research study skills social tolcapone

项目摘要

The broad, long-tenn objectives of this proposal are to develop better treatments for frontotemporal dementia (FTD). The Specific Aims are to: 1) Develop an effective therapeutic intervention for the treatment of FTD. To achieve this aim, the proposed project will test the clinical and cognitive effects on FTD patients of a medication that increases the amount of the neurotransmitter dopamine in the brain. This medication acts by inhibiting an enzyme, catechol 0-methyl-transferase (COMT), that degrades dopamine. The proposed project will also use fMRI to determine the effects of COMT inhibition on prefrontal cortex and temporal lobe efficiency while the patients read words that describe animal functions and social attributes. 2) Determine the effect of COMT genotype on symptom presentation and disease course in FTD patients. The COMT gene has a common polymorphism that affects its function. The Research Design is a 24-day double-blind, placebo-controlled crossover trial of 28 patients with FTD. The Methods to be used are a comparison of measures of behavioral and cognitive symptoms, and fMRI blood oxygenation level-dependent (BOLD) activation in the prefrontal cortex and temporal lobe, when the patients are taking a COMT inhibitor versus when they are taking a placebo. Frontotemporal dementia Is an illness that results in the degeneration of the frontal aspect of the brain. This study will test whether increasing a brain chemical, called dopamine, that is deficient in the brains of patients with frontotemporal dementia patients improves the symptoms of the illness. It will also use brain imaging and genetics to detemnlne the contribution of dopamine deficiency to the symptoms ofthis illness.

该提案的广泛、长期目标是开发更好的额颞叶治疗方法痴呆症（FTD）。具体目标是： 1) 制定治疗 FTD 的有效治疗干预措施。为了实现这一目标，拟议的项目将测试一种增加大脑中神经递质多巴胺含量的药物对 FTD 患者的临床和认知效果。这种药物通过抑制儿茶酚 0-甲基转移酶 (COMT) 来发挥作用，这种酶可以降解多巴胺。该项目还将使用功能磁共振成像来确定患者阅读描述动物功能和社会属性的单词时 COMT 抑制对前额皮质和颞叶效率的影响。 2) 确定 COMT 基因型对 FTD 患者症状表现和病程的影响。 COMT 基因具有影响其功能的常见多态性。该研究设计是一项为期 24 天的双盲、安慰剂对照交叉试验，受试者为 28 名 FTD 患者。使用的方法是比较患者服用 COMT 抑制剂与服用安慰剂时的行为和认知症状测量值，以及前额皮质和颞叶的 fMRI 血氧水平依赖性 (BOLD) 激活。额颞叶痴呆是一种导致大脑额叶退化的疾病。这项研究将测试增加额颞叶痴呆患者大脑中缺乏的一种名为多巴胺的大脑化学物质是否可以改善疾病症状。它还将使用脑成像和遗传学来确定多巴胺缺乏对这种疾病症状的影响。