Dopamine and choline transporter imaging in DLB & AD

DLB 中的多巴胺和胆碱转运蛋白成像

• 批准号: 7238573
• 负责人: ERIC C. PETRIE
• 金额: $ 15.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7238573
• 关键词: Activities of Daily Living; Address; Aging; Alleles; Alzheimer' s Disease; American; Applications Grants; Attention; Auditory Hallucination; Autopsy; Award; Behavior Disorders; Behavioral Sciences; Binding; Biological; Biological Markers; Boston; Brain; Businesses; Cell membrane; Choline; Cholinergic Agents; Clinical; Clinical Research; Cognitive; Commit; Conflict of Interest; Contract Services; Corpus striatum structure; Correlative Study; Cross-Sectional Studies; D-4-chloro-17 beta-hydroxy-3-oxo-17 alpha-methylandrosta-1,4-diene; Delusions; Dementia; Digit structure; Discipline of Nuclear Medicine; Disease; Disease Progression; Doctor of Medicine; Doctor of Philosophy; Dopamine; Education; Educational process of instructing; Employee; Exhibits; Extramural Activities; Faculty; Financial compensation; Geriatrics; Grant; Hallucinations; Healthcare Systems; Human; Image; Impaired cognition; Impairment; K-Series Research Career Programs; Language; Lewy Bodies; Lewy Body Disease; Life; Longitudinal Studies; Measures; Membrane Transport Proteins; Memory; Mental Health Services; Mental disorders; Mentored Clinical Scientist Development Award (K08); Motor; Names; Nature; Nerve; Nerve Degeneration; Neurobiology; Neurofibrillary Tangles; Numbers; Occipital lobe; Office of the Director; Parietal; Parkinsonian Disorders; Pathology; Patients; Pattern; Performance; Principal Investigator; Psychiatry; Radiology Specialty; Relative (related person); Research; Research Design; Research Personnel; Research Training; Robin bird; Senile Plaques; Services; Severities; Study Subject; Symptoms; Telefacsimile; Telephone; Temporal Lobe; Testing; Time; United States; United States National Institutes of Health; Universities; Visual Hallucination; Visuospatial; Washington; Wisconsin; Work; Writing; apolipoprotein E-4; base; caudate nucleus; choline transporter; cholinergic; cholinergic neuron; cognitive function; design; dopaminergic neuron; early onset; executive function; experience; follow-up; genetic risk factor; in vivo; interest; medical schools; member; neurochemistry; neuroimaging; neuron loss; professor; programs; research study; single photon emission computed tomography; skills; sound; vigilance

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two most common causes of dementia. AD is characterized by initial deficits in memory and language function while DLB is characterized by initial deficits in: i) attention, frontal-subcortical/executive function, and yisuospatial/praxis skills; ii) parkinsonian motor signs; and iii) persistent visual hallucinations. Differences in striatal dopaminergic and cortical cholinergic neuron integrity have been implicated in the contrasting clinical presentations of AD and DLB in cross-sectional studies. The candidate proposes to employ a longitudinal design to identify temporal correlations between in vivo biomarkers of cortical cholinergic and striatal dopaminergic neuron integrity (assessed via SECT imaging of 123I-IBVM choline vesicular transporter [CVT] and 99mTc-TRODAT-1 dopamine plasma membrane transporter [DMT] binding) and measures of cognitive, parkinsonian, and psychotic symptoms in AD, DLB, and normal older control subjects(NOCS). Specific Aim 1: Identify temporal relationships between striatal dopaminergic neuron integrity and differential patterns of cognitive impairment and parkinsonian signs in DLB, AD, and NOCS over a four-year follow-up period. Hypothesis 1a: Striatal 99mTC-TRODAT-1 DMT binding will be positively correlated with attention (Digit Vigilance test) and frontal-subcortical, executive function (Self-Oriented Pointing Test) in DLB, AD, and normal older subjects at 0, 2, & 4 years. Attention and frontal-subcortical/executive function will be more impaired and 99mTc-TRODAT-1 binding lower in DLB > AD > NOCS at all time points. Hypothesis 1b: Striatal 99mTc-TRODAT-1 DMT binding will be inversely related to parkinsonian signs in DLB and AD at 0,2, & 4 years. Parkinsonian signs and loss of 99mTc-TRODAT-1 binding will be more severe in DLB > AD > NOCS at all time points. Specific Aim 2: Identify temporal relationships between cortical cholinergic neuron integrity and differential patterns of cognitive impairment in DLB, AD, and NOCS over a four-year follow-up period. Hypothesis 2a: 123I-IBVM CVT binding in temporal cortex will be negatively correlated with memory (Wechsler logical memory scale) and language (Boston Naming Test) function in AD, DLB, and normal older subjects at 0, 2, & 4 years. Memory and language impairment and loss of 123I-IBVM binding will be more severe in AD > DLB > NOCS at all time points. Hypothesis 2b: 123I-IBVM CVT binding in parietal and occipital cortex will be inversely related to visuospatial/praxis abilities (Wechsler block design) at 0, 2, & 4 years. Impairment in visuospatial/praxis abilities and loss of 123I-IBVM binding will be greater in DLB > AD > NOCS at all time points. Specific Aim 3: Characterize relationships between cholinergic and dopaminergic neuron integrity and psychotic symptoms in DLB and AD and demonstrate persistence over time. Hypothesis 3: Temporal lobe CVT binding will be inversely related to visual hallucinations in DLB and auditory hallucinations in AD at 0, 2, & 4 years.

描述（由申请人提供）：阿尔茨海默氏病（AD）和Lewy尸体（DLB）是痴呆症的两个最常见原因。 AD的特征是记忆和语言功能的初始缺陷，而DLB的特征在于：i）注意力，额叶 - 皮层/执行功能以及Yisuospatial/Praxis技能； ii）帕金森汽车标志； iii）持续的视觉幻觉。在横断面研究中，纹状体多巴胺能和皮质胆碱能神经元完整性的差异与AD和DLB的对比临床表现有关。候选人提议采用纵向设计，以确定皮质胆碱能体内生物标志物与纹状体多巴胺能神经元完整性之间的时间相关性（通过123i-ibvm胆碱囊囊囊群的群体成像评估AD，DLB和正常旧对照受试者（NOC）中认知，帕金森氏症和精神病症状的认知，帕金森氏症和精神病症状。 具体目的1：在四年的随访期内，在DLB，AD和NOC中确定纹状体多巴胺能神经元完整性与认知障碍和帕金森氏症标志的差异模式之间的时间关系。 假设1A：纹状体99MTC-TrodoDat-1 DMT结合将与注意力（数字警惕性测试）和DLB，AD和正常受试者在0、2和4年中的注意力（数字警惕性测试）和额叶皮质的执行功能（自我导向指向测试）正相关。注意力和额叶/执行功能将受到更大的损害，并且在所有时间点DLB> ad> noc中的99mtc-Trododat-1结合。假设1b：纹状体99MTC-TrodoDat-1 DMT结合将与DLB中的帕金森氏症符号成反比，在0,2和4年时AD中的tagins符号。帕金森氏症的体征和99mtc-Trododat-1结合的损失将在始终的DLB> AD> NOC中更为严重。 特定目的2：在四年的随访期内，确定在DLB，AD和NOC中认知障碍的皮质胆碱能神经元完整性与差异模式之间的时间关系。假设2a：颞皮质中的123i-ibvm CVT结合将与记忆（Wechsler逻辑记忆量表）和语言（波士顿命名测试）在AD，DLB和正常老年受试者（在0、2和4年中）负相关。在所有时间点，在AD> DLB> NOC中，记忆和语言障碍和123I-IBVM结合的损失将更加严重。 假设2b：在0、2和4岁时，在顶叶和枕皮层中的123-IBVM CVT结合将与0、2和4年的视觉空间/实践能力（Wechsler Block Design）成反比。视觉空间/实践能力的损害和123I-IBVM结合的损失在始终的DLB> AD> NOC中会更大。 特定目的3：表征DLB和AD中胆碱能和多巴胺能神经元完整性与精神病症状之间的关系，并且随着时间的推移表现出持久性。 假设3：颞叶CVT结合将与DLB的视觉幻觉和AD的听觉幻觉成反比，在0、2和4年。