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

项目概要/摘要 睡眠中断和相关的日间功能障碍在帕金森病（PD）患者中很常见， 影响了80%的患者。尽管这种已知的普遍存在的睡眠-觉醒障碍， 了解功能失调的睡眠-觉醒节律如何导致认知和神经精神症状 PD痴呆症（PDD）和密切相关的路易体痴呆症（DLB）。大脑的许多区域 参与调节日常睡眠-觉醒行为模式的神经元也最早受到路易体的影响 (LB)在PD和DLB患者中，阿尔茨海默病（AD）病理学以及共同发生的阿尔茨海默病（AD）病理学的变化。这 行政补充申请补充资金，以调查 睡眠-觉醒行为模式中断、AD共病以及认知和神经精神进展， 路易体病的背景。我们将应用新的分析技术，如功能原理， 成分分析，新获得的连续24小时高分辨率体动记录数据，以评估模式 PD和DLB患者的睡眠-觉醒行为。独特地利用PET和CSF生物标志物， tau共同病理学，我们将量化纯LB患者的睡眠-觉醒行为模式 和混合LB/AD病理。本研究的目的是：（1）确定中断模式的关联 PD和DLB患者的睡眠-觉醒行为与认知能力和神经精神障碍的关系， 和（2）将睡眠-觉醒行为表型与PD中tau共同病理学的生物标志物（PET和CSF）相关联， DLB。 拟定研究对NOT-NS-21-040“合作研究管理补充文件”的响应度很高。 促进ADRD睡眠/昼夜节律研究的活动”及其既定目标“，以促进合作 更好地了解慢性睡眠障碍/昼夜节律之间的双向关系的研究 破坏和AD/ADRD发病机制”。这一补充也代表了一个新的合作努力， 睡眠研究人员（Jamie Zeitzer博士）和来自父母资助的PD/AD研究人员（Poston博士和 Andreasson），a提供了一个独特的机会来研究睡眠-觉醒节律在睡眠中的作用。 患者中与单纯LB和混合LB/AD病理学相关的认知障碍和痴呆的进展 与PD和DLB合作

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.