Dopamine and choline transporter imaging in DLB & AD

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的特征在于记忆和语言功能的初始缺陷，而DLB的特征在于以下方面的初始缺陷：i）注意力、额叶-皮层下/执行功能和意识空间/实践技能; ii）帕金森运动体征;和iii）持续性幻视。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在横断面研究中的对比临床表现有关。候选人提出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123 I-IBVM胆碱囊泡转运蛋白[CVT]和99 mTc-TRODAT-1多巴胺质膜转运蛋白[DMT]结合的SECT成像评估）和AD、DLB、正常老年对照组（NOCS）。 具体目标1：在为期4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：纹状体99 mTC-TRODAT-1 DMT结合将与DLB、AD和正常老年受试者在0、2和4岁时的注意力（数字警戒测试）和额叶皮层下执行功能（自我定向指向测试）正相关。在所有时间点，DLB > AD > NOCS的注意力和额叶皮层下/执行功能将更受损，99 mTc-TRODAT-1结合更低。假设1b：纹状体99 mTc-TRODAT-1 DMT结合与0、2和4年时DLB和AD的帕金森症状呈负相关。在所有时间点，DLB > AD > NOCS中帕金森症状和99 mTc-TRODAT-1结合的丧失将更严重。 具体目标二：在为期4年的随访期内，确定DLB、AD和NOCS中皮质胆碱能神经元完整性与认知障碍差异模式之间的时间关系。假设2a：颞叶皮质中的123 I-IBVM CVT结合将与AD、DLB和正常老年受试者在0、2和4岁时的记忆（韦氏逻辑记忆量表）和语言（波士顿记忆测验）功能负相关。在所有时间点，AD > DLB > NOCS中的记忆和语言损伤以及123 I-IBVM结合的丧失将更严重。 假设2b：顶叶和枕叶皮质中的123 I-IBVM CVT结合将与0、2和4年时的视觉空间/实践能力（Wechsler区组设计）负相关。在所有时间点，DLB > AD > NOCS中视觉空间/实践能力的损害和123 I-IBVM结合的损失将更大。 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。 假设三：颞叶CVT结合将与0、2和4年时DLB中的幻视和AD中的幻听负相关。

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.