MONOAMINERGIC PATHWAYS IN NEURODEGENERATIVE DISEASES

神经退行性疾病中的单胺能途径

• 批准号: 6315624
• 负责人: SID GILMAN
• 金额: $ 22.35万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6315624
• 关键词: Alzheimer's disease; Lewy body; aging; basal ganglia; bioimaging /biomedical imaging; brain metabolism; carbon; clinical research; cognition disorders; dementia; deoxyglucose; diagnosis quality /standard; glucose metabolism; human subject; neural degeneration; neuropathology; neuropsychological tests; occipital lobe /cortex; positron emission tomography; radionuclides; synaptic vesicles; visual cortex

This is an application for competing continuation of an ongoing project currently designed to test five hypotheses. (1) The densities of striatal of monoaminergic presynaptic terminals are markedly decreased in patients with clinically diagnosed dementia with Lewy bodies (DLB), and mildly reduced or unchanged in patients with clinically diagnosed Alzheimer's disease without extrapyramidal signals (Adw/oEPs). Positron emission tomography (PET) scanning with (+)[11C]dihydrotetrabenazine will be performed in patients meeting current clinical criteria for DLB and AD2/oEPs, and in elderly normal control subjects, with approximately the same level of dementia (clinical dementia rating scale 3 or 4) in the two patient groups. (2) In patients with clinical diagnosed DLB, the densities of striatal monoaminergic presynaptic terminals are negatively correlated with the intensity of the extrapyramidal features detected clinically. Correlations will be made between the densities of striatal monoaminergic presynaptic terminals and the intensity of the extrapyrimidal features as determined at the time of scanning with the Unified Parkinson's Disease Rating Scale by a clinician blinded to the results of the PET studies. (3) Local cerebral metabolic rates for glu8cose (lCMRglc) in the medial occipital lobes are markedly decreased in patients with clinically diagnosed DLB, and mildly reduced or unchanged in patients in patients with clinically diagnosed AD2/oEPs. PET with [18F]fluorodeoxyglucose will be performed in patients with DLB and AD2/oEPs and in the elderly normal control subjects identified in hypothesis 1, and medial occipital lCMRglc will be compared between groups. (4) In clinically diagnosed DLB, lCMRglc in the medial occipital lobes is positively correlated with the severity of visuospatial of visuoconstructive disorders. Correlations will be made between medial occipital lCMRglc and the results of neuropsychological tests of visual functioning in the DLB patients identified in hypothesis 1. (5) Measures of striatal monoaminergic presynaptic terminal density and of accuracy even further. Patients with DLB and AD2/oEPs studies in this project will be followed to postmortem examination for neuropathological diagnosis, and the accuracy of the clinical diagnostic criterial alone will be compared with the results of including measures of striatal monoaminergic presynaptic terminal density and of medial occipital lCMRglc.

这是一项竞争性延续正在进行的项目的申请，该项目目前旨在测试五个假设。 (1)临床诊断的路易体痴呆(DLB)患者的单胺能突触前末梢纹状体密度明显降低，临床诊断的无锥体外系信号的阿尔茨海默病(Adw/oEPs)患者的纹状体密度轻度降低或无变化。 将在符合当前 DLB 和 AD2/oEP 临床标准的患者以及老年正常对照受试者中使用 (+)[11C]二氢丁苯那嗪进行正电子发射断层扫描 (PET) 扫描，两个患者组中痴呆水平大致相同（临床痴呆评级量表 3 或 4）。 (2)在临床诊断的DLB患者中，纹状体单胺能突触前末梢的密度与临床检测到的锥体外系特征的强度呈负相关。纹状体单胺能突触前末梢的密度与锥体外系特征的强度之间存在相关性，由对 PET 研究结果不知情的临床医生使用统一帕金森病评定量表进行扫描时确定。 (3)临床诊断的DLB患者枕叶内侧局部葡萄糖代谢率(lCMRglc)显着降低，临床诊断的AD2/oEP患者轻度降低或无变化。将在患有 DLB 和 AD2/oEP 的患者以及假设 1 中确定的老年正常对照受试者中进行 [18F] 氟脱氧葡萄糖 PET，并对组间内侧枕叶 lCMRglc 进行比较。 (4)临床诊断的DLB中，枕叶内侧lCMRglc与视觉结构障碍的视觉空间严重程度呈正相关。将在假设 1 中确定的 DLB 患者的内侧枕叶 lCMRglc 和视觉功能神经心理学测试结果之间建立相关性。 (5) 纹状体单胺能突触前末梢密度的测量和进一步的准确性。本项目中进行 DLB 和 AD2/oEPs 研究的患者将进行尸检以进行神经病理学诊断，并将单独的临床诊断标准的准确性与纹状体单胺能突触前末梢密度和内侧枕叶 lCMRglc 测量结果进行比较。