MONOAMINERGIC PATHWAYS IN NEURODEGENERATIVE DISEASES

这是一个正在进行的项目的竞争性延续申请，目前旨在测试五个假设。(1)临床诊断为路易体痴呆（DLB）的患者单胺能突触前终末纹状体密度明显降低，临床诊断为无锥体外信号（Adw/oEPs）的阿尔茨海默病患者纹状体密度轻度降低或保持不变。符合DLB和AD2/oEPs临床标准的患者，以及两组痴呆水平大致相同（临床痴呆评定量表3或4）的老年正常对照患者，将使用（+）[11C]二氢四苯那嗪进行正电子发射断层扫描（PET）。(2)在临床诊断为DLB的患者中，纹状体单胺能突触前终末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终末的密度与锥体外特征的强度之间将建立相关性，这些特征是由临床医生在对PET研究结果不知情的情况下使用统一帕金森病评定量表进行扫描时确定的。(3)临床上诊断为DLB的患者枕叶内侧局部脑葡萄糖代谢率（lCMRglc）明显降低，临床上诊断为AD2/oEPs的患者轻度降低或保持不变。对DLB和AD2/oEPs患者以及假设1中确定的老年正常对照进行[18F]氟脱氧葡萄糖PET，比较两组间枕部内侧lCMRglc。(4)在临床诊断为DLB的患者中，枕叶内侧lCMRglc与视觉建构性障碍的视觉空间严重程度呈正相关。假设1中确定的DLB患者的视觉功能神经心理测试结果与枕内侧lCMRglc之间存在相关性。纹状体单胺能突触前终末密度的测定及其准确性。本项目将对DLB和AD2/oEPs患者进行死后随访，进行神经病理诊断，并将单独的临床诊断标准与纹状体单胺能突触前终末密度和枕内侧lCMRglc测量结果进行比较。

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.