Dopamine and choline transporter imaging in DLB & AD

描述(申请人提供)：阿尔茨海默病(AD)和路易体痴呆(DLB)是导致痴呆症的两个最常见的原因。AD的特征是记忆和语言功能的初始缺陷，而DLB的特征是：i)注意力、额叶皮质下/执行功能和空间/实践技能的初始缺陷；ii)帕金森病的运动体征；以及iii)持续性的视觉幻觉。在横断面研究中，纹状体多巴胺能神经元和皮质胆碱能神经元完整性的差异与AD和DLB的不同临床表现有关。候选人建议采用纵向设计，以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记物(通过123I-IBVM胆碱囊泡转运体[CVT]和99mTC-TRODAT-1多巴胺质膜转运体[DMT]结合的切片成像进行评估)与AD、DLB和正常老年对照组受试者(NOCS)认知、帕金森和精神病症状的测量之间的时间相关性。 具体目标1：确定纹状体多巴胺能神经元完整性与认知损害和帕金森症状的不同模式之间的时间关系，在四年的随访期内，这些患者分别为DLB、AD和NOCS。假设1a：在0岁、2岁和4岁时，纹状体99mTC-TRODAT-1 DMT结合与注意力(数字警戒测试)和额叶-皮质下执行功能(自我定向指向测试)呈正相关。注意和额叶-皮质下/执行功能在所有时间点都会受到更多的损害，99mTC-TRODAT-1结合率在所有时间点都会降低。假设1b：纹状体99mTC-TRODAT-1DMT结合与0、2和4年的DLB和AD的帕金森症状呈负相关。在所有时间点，DLB&GT；AD&GT；NOCS的帕金森症状和99mTC-TRODAT-1结合丢失将更加严重。具体目标2：在四年的随访期内，确定皮质胆碱能神经元完整性与DLB、AD和NOCS患者认知损害的不同模式之间的时间关系。假设2a：在0、2和4岁的AD、DLB和正常老年人中，颞叶皮质中123I-IBVM CVT的结合与记忆(韦氏逻辑记忆量表)和语言(波士顿命名测试)功能呈负相关。记忆和语言的损伤以及123I-IBVM结合的丧失在AD&>；DLB&>NOCS的所有时间点都将更加严重。假设2b：在0、2和4年，顶叶和枕叶皮质中的123I-IBVM CVT结合将与视觉空间/实践能力呈负相关(韦氏区块设计)。在所有时间点，视觉空间/练习能力的损害和123I-IBVM结合的丧失在DLB&>AD&>NOCS中都会更严重。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和精神症状之间的关系，并展示随时间推移的持久性。假设3：在0、2、4岁时，颞叶CVT结合与DLB患者的视觉幻觉和AD患者的听觉幻觉呈负相关。

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.