MONOAMINERGIC PATHWAYS IN NEURODEGENERATIVE DISEASES

这是一个正在进行的项目的竞争延续申请，目前该项目旨在测试五个假设。(1)临床诊断为路易体痴呆(DLB)的阿尔茨海默病(ADW/OEPS)患者纹状体单胺能突触前终末密度明显降低，而临床诊断为阿尔茨海默病(ADW/OEPS)的患者纹状体密度略有降低或无变化。符合当前DLB和AD2/OEPS临床标准的患者以及两组痴呆症水平大致相同(临床痴呆症分级3或4级)的老年正常对照受试者将接受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密度与临床发现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将与临床医生在不了解PET研究结果的情况下用统一的帕金森病分级量表扫描时所确定的锥体外区特征的强度相关联。(3)临床诊断为DLB的患者枕叶内侧局部脑葡萄糖代谢率(1CMRglc)显著降低，而临床诊断为AD2/OEPS的患者局部脑组织葡萄糖代谢率轻度降低或无明显变化。在DLB和AD2/OEPS患者和假设1中确定的老年正常受试者中，将进行带有[18F]氟脱氧葡萄糖的PET检查，并比较两组之间枕骨内侧LCMRglc的差异。(4)在临床诊断的DLB中，枕叶内侧的LCMRglc与视空间功能障碍的严重程度呈正相关。将在枕内侧LCMRglc与假说1中确定的DLB患者的视觉功能神经心理测试结果之间建立相关性。(5)纹状体单胺能突触前终末密度的测量和进一步的准确性。在本项目中，DLB和AD2/OEPS研究的患者将被跟踪进行神经病理诊断的尸检，并将临床诊断标准的准确性单独与包括纹状体单胺能突触前终末密度和枕内侧LCMRglc的测量结果进行比较。

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.