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

帕金森病的视幻觉和记忆障碍：海马网络的作用

• 批准号: 10471165
• 负责人: Arnold Bakker
• 金额: $ 61.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10471165
• 关键词: Affect; Animals; Anxiety; Area; Bradykinesia; Brain imaging; Brain region; Caregiver Burden; Characteristics; Clinical; Clinical assessments; Cognitive; Data; Dementia; Development; Diagnosis; Episodic memory; Etiology; Executive Dysfunction; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Hallucinations; High Prevalence; Hippocampus (Brain); Human; Hyperactivity; Impaired cognition; Impairment; Individual; Intervention; Light; Link; Measures; Medial; Memory; Memory impairment; Mental Depression; Methods; Nerve Degeneration; Neurobehavioral Manifestations; Neuropsychology; Nursing Homes; Parkinson Disease; Participant; Patients; Play; Predictive Value; Process; Psychoses; Psychotic Disorders; Quality of life; Reporting; Resolution; Rest; Risk; Role; Structure; Symptoms; Taxes; Temporal Lobe; Testing; Tremor; Visual Hallucination; Work; advanced disease; base; behavior test; cognitive impairment in Parkinson' s; cognitive task; cognitive testing; common symptom; daily functioning; dementia risk; dentate gyrus; design; disability; episodic memory impairment; experience; follow-up; functional decline; functional disability; hippocampal subregions; imaging biomarker; imaging modality; insight; memory recall; mortality; motor symptom; network dysfunction; neuroimaging; neuropsychiatric symptom; non-motor symptom; novel therapeutic intervention; novel therapeutics; patient subsets; prognostic value; psychiatric symptom; visual memory

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.

项目总结 帕金森氏病(PD)的诊断依据是其特有的运动迟缓症状， 僵硬和震颤。越来越多的神经精神症状被认为是神经退行性疾病的一部分。 帕金森病过程。认知障碍和精神病随着帕金森病的进展而增加，并与 照顾者负担、日常功能受损和养老院安置、痴呆症和更高的死亡率。 具体地说，记忆障碍和幻觉发生在帕金森病患者的一部分中，并与 患痴呆症和功能障碍的风险增加。众所周知，海马体是至关重要的 对记忆功能和海马体功能障碍的重要作用已被证明对 许多人类和动物研究中的记忆障碍。同样，现在人们认识到，海马体 在各种精神障碍的幻觉病因中扮演着重要的角色。然而，它的作用是 帕金森病残留物记忆障碍和幻觉平行临床过程中的海马区网络 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 帕金森病患者记忆障碍和幻觉的机制，并确定在特定情况下活动增加是否 海马区预示着更大的认知和功能纵向衰退。 目前的项目旨在通过详细的神经心理评估和高 帕金森病伴情节记忆患者的分辨功能磁共振成像方法 有幻觉的帕金森病患者，没有间歇性记忆障碍或幻觉的帕金森病患者， 和健康的对照组。将采用有针对性的fmri激活任务来对海马区征税。 特定的功能。高分辨率静息状态功能磁共振成像将用于评估 海马区和皮层网络。临床和认知评估将在两年的随访中重复进行 为了评估这些功能磁共振标志物在认知和认知功能障碍进展中的纵向变化和预测价值 帕金森病的功能衰退。 总之，这项拟议的研究将深入了解海马体网络在记忆中的作用 帕金森病的损害和幻觉。这一结果将决定海马亚区功能障碍 是帕金森病患者间歇性记忆损害和幻觉的标志，也是风险增加的预测因子 以应对未来这一亚群患者的下降。最后，如果成功，这项工作将另外提供一个目标 针对帕金森病患者记忆障碍和幻觉的新治疗干预措施的开发。