Cognitive Impairment and Decline in Parkinson Disease

项目1 帕金森病的认知功能损害和衰退 帕金森病（PD）中期和晚期最常见和致残的发展之一 是认知障碍的发展，导致痴呆症。具体机制导致 PD中的痴呆症目前尚不清楚。然而，PD脑的死后病理检查 揭示了基底前脑和大脑皮层的退行性变化，这可能是痴呆症的原因。 晚期疾病此外，还有不同比例的痴呆PD患者，其中一些患者 也可看到阿尔茨海默病（AD）的典型变化。重要的是要更好地了解 导致PD痴呆的机制，作为运动症状的改善治疗， 脑干多巴胺能神经元逐渐丧失。如果这些治疗不能解决 导致PD中更广泛病理学的过程，PD中的总体发病率和死亡率可能不是 提高 在本项目中，我们将招募和描述一组中度运动性PD患者 严重程度，以及痴呆症发展风险增加的人。我们将进行行为和 基线认知测试，以及多巴胺能变性和基底前脑的PET成像 放射性示踪剂[11C]DTBZ用于绘制囊泡单胺转运蛋白结合的胆碱能变性 位点和[11 C]PMP分别测量乙酰胆碱酯酶水解率。我们还将 用[11 C]PIB进行成像，以检测病理性皮质内A3淀粉样蛋白沉积 (the AD的“老年”斑块）。患者将接受2年以上的前瞻性随访， 神经心理测量以确定间隔认知下降。我们将评估 PET神经退行性指标与认知功能丧失之间的关系， 可能存在的神经化学机制。此外，我们还将进行多变量分析， PET测量以评估可能存在的连接多巴胺能和胆碱能的全局过程 变性和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.