The impact of early Tau pathology on cognitive progression and neuropsychiatric symptoms in Parkinson's disease

早期 Tau 病理学对帕金森病认知进展和神经精神症状的影响

• 批准号: 10401958
• 负责人: Katrin I. Andreasson
• 金额: $ 39.29万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10401958
• 关键词: Address; Administrative Supplement; Affect; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Amyloid; Attenuated; Autopsy; Award; Behavior; Biological Markers; Brain region; Cause of Death; Chronic; Circadian Dysregulation; Clinical; Clinical assessments; Cognition; Cognitive; Collaborations; Collection; Data; Dementia; Dementia with Lewy Bodies; Development; Disease; Executive Dysfunction; Exhibits; Family; Functional disorder; Funding; Goals; Hour; Impaired cognition; Intervention; Investigation; Lewy Bodies; Lewy Body Disease; Magnetic Resonance Imaging; Measures; Medial; Mediation; Memory; Memory Loss; Memory impairment; Methods; Monitor; Neurobehavioral Manifestations; Parents; Parkinson Disease; Parkinson' s Dementia; Participant; Pathogenesis; Pathology; Pathway interactions; Patients; Pattern; Performance; Phenotype; Physiology; Polysomnography; Positron-Emission Tomography; Prevalence; Principal Component Analysis; Proxy; Psychoses; Research; Research Personnel; Resolution; Role; Severities; Sleep; Sleep Fragmentations; Sleep disturbances; Sleeplessness; Techniques; Temporal Lobe; Work; actigraphy; behavioral phenotyping; circadian; cognitive performance; cohort; disability; disability-adjusted life years; improved; innovation; interest; mixed dementia; neuropsychiatric symptom; neuropsychiatry; novel; parent grant; patient population; prevent; recruit; sleep pattern; tau Proteins; therapeutic development; therapeutically effective

PROJECT SUMMARY/ABSTRACT Sleep disruption and related daytime dysfunction are common in people with Parkinson’s disease (PD), affecting up to 80% of patients. Despite this known prevalence of sleep-wake disturbance, it is not well understood how dysfunctional sleep-wake rhythms may contribute to cognitive and neuropsychiatric symptoms in PD Dementia (PDD) and the closely related Dementia with Lewy Bodies (DLB). Many of the brain regions involved in regulating daily patterns of sleep-wake behavior are also the earliest to be affected by Lewy Body (LB) pathology, as well as by co-occurring Alzheimer’s disease (AD) pathology, in PD and DLB patients. This Administrative Supplement requests supplemental funding in order to investigate associations between disrupted patterns of sleep-wake behavior, AD co-pathology, and cognitive and neuropsychiatric progression in the context of Lewy body diseases. We will apply novel analysis techniques, such as functional principle component analysis, to newly acquired continuous 24-hour high-resolution actigraphy data to assess patterns of sleep-wake behavior in PD and DLB patients. Uniquely leveraging PET and CSF biomarkers of concomitant tau co-pathology from the parent grant, we will quantify patterns of sleep-wake behavior in patient with pure LB and mixed LB/AD pathologies. The Aims of this study are: (1) to determine associations of disrupted patterns of sleep-wake behavior with cognitive performance and with neuropsychiatric disturbances in PD and DLB., and (2) to relate sleep-wake behavior phenotypes to biomarkers of tau co-pathology (PET and CSF) in PD and DLB. The proposed studies are highly responsive to NOT-NS-21-040 “Administrative Supplements for Collaborative Activities to Promote Sleep/Circadian Research in ADRD” and its stated goal “to facilitate collaborative research to better understand the bi-directional relationship between chronic sleep disturbances/circadian disruption and AD/ADRD pathogenesis”. This supplement also represents a new collaborative effort between sleep researchers (Dr. Jamie Zeitzer) and PD/AD researchers from the parent grant (Drs. Poston and Andreasson), and a provides a unique opportunity to examine the role of sleep-wake rhythms in the progression of cognitive impairment and dementia related to pure LB and to mixed LB/AD pathology in patients with PD and DLB.

项目摘要/摘要 在帕金森氏病（PD）的患者中，睡眠中断和相关的白天功能障碍很常见， 影响多达80％的患者。尽管已知的睡眠 - 沃克灾难的流行率并不顺利 了解功能失调的睡眠唤醒节奏可能导致认知和神经精神症状 在PD痴呆症（PDD）和与Lewy Bodies（DLB）的密切相关的痴呆症中。许多大脑区域 参与控制睡眠觉醒行为的每日模式也是最早受Lewy身体影响的 （LB）PD和DLB患者的病理以及通过同时发生的阿尔茨海默氏病（AD）病理学。这 行政补充要求补充资金，以调查 睡眠效果行为的破坏模式，AD co病理学以及认知和神经精神病学的进展 路易人身体疾病的背景。我们将应用新颖的分析技术，例如功能原理 组件分析，到新获得的连续24小时高分辨率行影摄影数据以评估模式 PD和DLB患者的睡眠效果行为。独特利用伴随的宠物和CSF生物标志物 父母赠款的tau共同病理学，我们将量化纯LB患者的睡眠效果行为模式 和混合LB/AD病理。这项研究的目的是：（1）确定破坏模式的关联 在PD和DLB中，与认知表现以及神经精神灾难的睡眠效果行为。 （2）将睡眠效果行为表型与PD中的Tau co病理学（PET和CSF）的生物标志物相关联 DLB。 拟议的研究对Not-NS-21-040的响应高度敏感 在ADRD促进睡眠/昼夜研究的活动”及其既定目标” 研究以更好地了解慢性睡眠障碍/昼夜节律之间的双向关系 破坏和AD/ADRD发病机理”。这种补充也代表了两者之间的新协作努力 睡眠研究人员（Jamie Zeitzer博士）和父母赠款的PD/AD研究人员（Poston博士和 Andreasson），A提供了一个独特的机会，可以检查睡眠效果节奏在 与纯LB和患者混合LB/AD病理有关的认知障碍和痴呆症的进展 与PD和DLB。