Cognitive Impairment and Decline in Parkinson Disease

项目1 帕金森病患者的认知障碍和认知功能下降 帕金森病(PD)中后期最常见和最严重的发展之一 是认知障碍的发展，导致痴呆症。具体机制(S)导致 帕金森病的痴呆症目前尚不清楚。然而，帕金森病脑的死后病理检查 揭示基底前脑和大脑皮层的退行性变化可能是痴呆的原因 晚期疾病。此外，还有不同比例的痴呆帕金森病患者，其中一些 阿尔茨海默病(AD)的典型变化也可以看到。重要的是要更好地理解 改善运动症状治疗帕金森病致痴呆的机制(S) 脑干多巴胺能神经元进行性丢失。如果这些治疗不能解决 导致帕金森病更广泛的病理过程，帕金森病的总体发病率和死亡率可能不是 改进了。 在本项目中，我们将招募和描述一组患有中度运动性帕金森病的帕金森病患者。 严重程度，以及罹患痴呆症的风险增加。我们将执行行为和 基线认知测试与多巴胺能变性和基底前脑的正电子发射计算机断层扫描 用放射性示踪剂[11C]DTBZ标记囊泡单胺转运体结合的胆碱能变性 位点和[11C]PMP分别测定乙酰胆碱酯酶水解率。我们还会另外 用[11C]PIB显像检测纤维状A3淀粉样蛋白在大脑皮层的病理性沉积 (AD的“老年”斑块)。患者将被前瞻性地跟踪2年以上，并进行重复治疗 神经心理测量学测量以确定认知间期下降。我们将评估两国关系 在PET神经退行性测量和认知功能丧失之间的时间推移，以解决 神经化学机制(S)可能存在。此外，我们还将对 评估可能存在的连接多巴胺能和胆碱能的全球过程的PET测量 退行性变与AF3淀粉样蛋白沉积的发展。

PROJECT 1 COGNITIVE IMPAIRMENT AND DECLINE IN PARKINSON DISEASE One of the most frequent and disabling developments in the mid- and later stages of Parkinson disease (PD) is the development of cognitive impairment, leading to dementia. The specific mechanism(s) leading to dementia in PD are at present unknown. However, postmortem pathological examinations of PD brains reveal degenerative changes in the basal forebrain and cerebral cortex that may account for dementia in advanced disease. In addition, there are variable proportions of demented PD patients in whom some changes typical of Alzheimer disease (AD) are seen also. It will be important to better understand the mechanism(s) leading to dementia in PD as improved treatments for the motor symptoms and the progressive losses of brainstem dopaminergic neurons are developed. If these treatments do not address the processes leading to more widespread pathology in PD, overall morbidity and mortality in PD may not be improved. In the present project, we will recruit and characterize a cohort of PD patients with moderate motor PD severity, and who are at increased risk for the development of dementia. We will perform behavioral and cognitive testing at baseline, together with PET imaging of dopaminergic degeneration and basal forebrain cholinergic degeneration with the radiotracers [11C]DTBZ to map vesicular monoamine transporter binding sites and [11C]PMP to measure acetylcholinesterase hydrolysis rates, respectively. We will additionally perform imaging with [11C]PIB to detect pathological cerebrocortical deposition of fibrillary A3 amyloid protein (the "senile" plaques of AD). Patients will be followed prospectively over 2 years with repeat neuropsychometric measures to determine interval cognitive decline. We will assess the relationships between the PET neurodegenerative measures and the loss of cognitive function over time to address the neurochemical mechanism(s) that may be present. In addition, we will conduct a multivariate analysis of the PET measures to assess the possible presence of a global process linking the dopaminergic and cholinergic degenerations and the development of Af3 amyloid deposition.