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: 10668429
• 负责人: Arnold Bakker
• 金额: $ 59.29万
• 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/10668429
• 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; Human; Hyperactivity; Impaired cognition; Impairment; Individual; Intervention; 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; behavior test; cognitive impairment in Parkinson' s; cognitive task; cognitive testing; common symptom; comparison control; daily functioning; dementia risk; dentate gyrus; design; disability; episodic memory impairment; experience; follow-up; functional decline; functional disability; hippocampal subregions; 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; 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; Human; Hyperactivity; Impaired cognition; Impairment; Individual; Intervention; 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; behavior test; cognitive impairment in Parkinson' s; cognitive task; cognitive testing; common symptom; comparison control; daily functioning; dementia risk; dentate gyrus; design; disability; episodic memory impairment; experience; follow-up; functional decline; functional disability; hippocampal subregions; 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.

项目摘要 帕金森氏病（PD）是根据其特征性运动症状诊断的， 僵化和震颤。越来越多的神经精神症状被确定为神经退行性的一部分 PD的过程。认知障碍和精神病随着PD的发展而增加，并与增加有关 护理人员负担，日常运作和疗养院安置，痴呆症和更大的死亡率。 具体而言，记忆障碍和幻觉发生在PD患者的一部分中，并且与 增加痴呆症和功能障碍的风险。众所周知，海马很关键 对于记忆功能和海马功能障碍至关重要 许多人类和动物研究中的记忆障碍。同样，现在已经认识到海马 在各种精神疾病的幻觉中起着重要的作用。但是， 在PD的平行临床过程中，海马网络的记忆力障碍和幻觉仍然存在 不清楚。该项目的目的是评估海马网络功能障碍是否提供了共享 记忆力障碍和PD幻觉的机制，并确定特定活动的活动是否增加 海马子区域纵向预测认知和功能下降。 当前的项目旨在使用详细的神经心理学评估和高度 - 在具有偶发记忆的PD患者中的分辨率功能磁共振成像（fMRI）方法 损害，具有幻觉的PD患者，无情节记忆障碍或幻觉的PD患者， 和健康对照。有针对性的FMRI激活任务将旨在征税海马子区域 具体功能。高分辨率静止状态fMRI将用于评估连通性的变化 海马和皮质网络。临床和认知评估将在两年的随访中重复 评估这些fMRI标记在认知和认知和 PD功能下降。 拟议的研究一起将洞悉海马网络在记忆中的作用 PD中的损害和幻觉。结果将确定海马子区域中的功能障碍是否 是PD患者的情节记忆障碍和幻觉的标志，并且预测风险增加 对于这一子集的未来下降。最后，如果成功的话，这项工作还将为 PD中新的治疗干预措施的新治疗干预措施。