Visual hallucinations and memory impairment in Parkinson's Disease: The role of hippocampal networks

项目摘要 帕金森病（PD）的诊断是基于其运动迟缓的特征性运动症状， 僵硬和震颤越来越多的神经精神症状被确定为神经退行性疾病的一部分， PD的过程。认知障碍和精神病随着PD进展而增加， 照顾者负担、日常功能受损和养老院安置、痴呆和死亡率增加。 具体而言，记忆障碍和幻觉发生在PD患者的一个子集中，并且与PD患者的症状相关。 痴呆和功能障碍的风险增加。众所周知海马体对于 对记忆功能和海马功能障碍很重要 在许多人类和动物研究中发现的记忆障碍。同样，现在人们认识到海马体 在各种精神障碍的幻觉病因学中起着重要作用。然而， 帕金森病患者记忆障碍和幻觉并行临床过程中的海马网络 不清楚该项目的目标是评估海马网络功能障碍是否提供了一个共享的 PD中记忆障碍和幻觉的机制，并确定是否在特定的 海马子区域预测纵向更大的认知和功能下降。 目前的项目旨在通过详细的神经心理学评估和高- PD患者情景记忆的功能磁共振成像（fMRI）方法 有幻觉的PD患者，无情景记忆障碍或幻觉的PD患者， 健康的对照。一个有针对性的功能磁共振成像激活任务将采用旨在征税海马亚区 具体功能。高分辨率静息态功能磁共振成像将用于评估 海马和皮层网络。临床和认知评估将在两年随访时重复进行 评估这些fMRI标记物在认知和认知障碍进展中的纵向变化和预测价值， PD功能下降。 这些研究将为海马网络在记忆中的作用提供新的见解 PD中的损伤和幻觉。结果将确定海马亚区功能障碍是否 是PD患者情景记忆障碍和幻觉的标志物，也是风险增加的预测因子 这部分患者的未来下降。最后，如果成功的话，这项工作将另外提供一个目标， 开发新的治疗帕金森病记忆障碍和幻觉的干预措施。

PROJECT SUMMARY Parkinson's disease (PD) is diagnosed based on its characteristic motor symptoms of bradykinesia, rigidity, and tremor. Increasingly, neuropsychiatric symptoms are identified as part of the neurodegenerative process of PD. Cognitive impairment and psychosis increase as PD advances and are associated with increased caregiver burden, impaired daily functioning and nursing home placement, dementia, and greater mortality. Specifically, memory impairment and hallucinations occur in a subset of PD patients and are associated with an increased risk for dementia and functional impairment. It is well established that the hippocampus is critically important for memory function and hippocampal dysfunction has been shown to significantly contribute to memory impairment in numerous human and animal studies. Similarly, it is now recognized that the hippocampus plays an important role in the etiology of hallucinations across various psychotic disorders. However, the role of hippocampal networks in the parallel clinical course of memory impairment and hallucinations in PD remains unclear. The goal of this project is to assess whether hippocampal network dysfunction provides a shared mechanism for memory impairment and hallucinations in PD and determine whether increased activity in specific hippocampal subregions predicts greater cognitive and functional decline longitudinally. The current project aims to achieve these goals using detailed neuropsychological assessment and high- resolution functional magnetic resonance imaging (fMRI) methods in PD patients with episodic memory impairment, PD patients with hallucinations, PD patients without episodic memory impairment or hallucinations, and healthy controls. A targeted fMRI activation task will be employed designed to tax hippocampal subregion specific functioning. High-resolution resting-state fMRI will be used to assess connectivity changes between hippocampal and cortical networks. Clinical and cognitive assessments will be repeated at a two-year follow up to assess longitudinal change and predictive value of these fMRI markers in the progression of cognitive and functional decline in PD. Together the proposed studies will provide insight into the role of the hippocampal network in memory impairment and hallucinations in PD. The results will determine whether dysfunction in hippocampal subregions is a marker of episodic memory impairment and hallucinations in PD patients and a predictor of increased risk for future decline in this subset of patients. Finally, if successful, this work would additionally provide a target for the development of new therapeutic interventions for memory impairment and hallucinations in PD.