MONOAMINERGIC PATHWAYS IN NEURODEGENERATIVE DISEASES

这是一个正在进行的项目，目前旨在测试五个假设的竞争继续应用程序。(1)临床诊断为路易体痴呆（DLB）的患者纹状体单胺能突触前终末密度显著降低，临床诊断为无锥体外系信号的阿尔茨海默病（Adw/oEPs）患者纹状体单胺能突触前终末密度轻度降低或无变化。 将在符合DLB和AD 2/oEP当前临床标准的患者和老年正常对照受试者中使用（+）[11 C]二氢丁苯那嗪进行正电子发射断层扫描（PET），两个患者组的痴呆水平（临床痴呆评定量表3或4）大致相同。(2)在临床诊断DLB的患者中，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。将在纹状体单胺能突触前末梢的密度与由对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扫描时确定的嘧啶外特征的强度之间建立相关性。(3)在临床诊断为DLB的患者中，内侧枕叶中葡萄糖的局部脑代谢率（lCMRglc）显著降低，在临床诊断为AD 2/oEP的患者中，该代谢率轻度降低或无变化。将在DLB和AD 2/oEP患者以及假设1中确定的老年正常对照受试者中进行[18 F]氟脱氧葡萄糖PET，并将在组间比较内侧枕叶lCMRglc。(4)在临床诊断的DLB中，内侧枕叶的lCMRglc与视觉结构障碍的视觉空间严重程度呈正相关。相关性将在内侧枕叶lCMRglc和假设1中确定的DLB患者的视觉功能的神经心理学测试结果之间进行。(5)纹状体单胺能突触前末梢密度的测量和更进一步的准确性。本项目中DLB和AD 2/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包括纹状体单胺能突触前终末密度和内侧枕叶lCMRglc测量的结果进行比较。

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.