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: 7432520
• 负责人: ERIC C. PETRIE
• 金额: $ 15.94万
• 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/7432520
• 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）：阿尔茨海默病（AD）和路易体痴呆（DLB）是痴呆的两种最常见原因。 AD 的特征是记忆和语言功能的初始缺陷，而 DLB 的特征是以下方面的初始缺陷： i) 注意力、额叶皮质下/执行功能和意空间/实践技能； ii) 帕金森运动体征； iii) 持续性幻视。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 的临床表现对比有关。候选人建议采用纵向设计来确定皮质胆碱能和纹状体多巴胺能神经元完整性的体内生物标志物之间的时间相关性（通过 123I-IBVM 胆碱囊泡转运蛋白 [CVT] 和 99mTc-TRODAT-1 多巴胺质膜转运蛋白的 SECT 成像进行评估[ DMT] 结合）以及 AD 中认知、帕金森病和精神病症状的测量， DLB 和正常老年对照受试者 (NOCS)。 具体目标 1：在四年的随访期内，确定 DLB、AD 和 NOCS 中纹状体多巴胺能神经元完整性与认知障碍和帕金森病体征的差异模式之间的时间关系。 假设 1a：在 DLB、AD 和正常老年受试者中，纹状体 99mTC-TRODAT-1 DMT 结合在 0、2、 ＆4年。在所有时间点，在 DLB > AD > NOCS 中，注意力和额叶皮质下/执行功能将受到更严重的损害，并且 99mTc-TRODAT-1 结合较低。假设 1b：纹状体 99mTc-TRODAT-1 DMT 结合与 0,2 和 4 岁时 DLB 和 AD 中的帕金森症状呈负相关。在所有时间点，DLB > AD > NOCS 中帕金森病症状和 99mTc-TRODAT-1 结合丧失都会更加严重。 具体目标 2：确定四年随访期间皮质胆碱能神经元完整性与 DLB、AD 和 NOCS 认知障碍差异模式之间的时间关系。假设 2a：颞叶皮层中的 123I-IBVM CVT 结合与 AD、DLB 和 0、2 和 4 岁正常老年受试者的记忆（韦克斯勒逻辑记忆量表）和语言（波士顿命名测试）功能呈负相关。在所有时间点，AD > DLB > NOCS 中记忆和语言障碍以及 123I-IBVM 结合丧失都会更加严重。 假设 2b：顶叶和枕叶皮质中的 123I-IBVM CVT 结合将与 0、2 和 4 岁时的视觉空间/实践能力（韦氏区组设计）呈负相关。在所有时间点，DLB > AD > NOCS 中视觉空间/实践能力的损伤和 1​​23I-IBVM 结合的丧失都会更大。 具体目标 3：描述 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，并证明随时间的持续性。 假设 3：颞叶 CVT 结合在 0、2 和 4 岁时与 DLB 中的视幻觉和 AD 中的幻听呈负相关。