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

项目摘要/摘要 睡眠障碍和相关的日间功能障碍在帕金森氏症(PD)患者中很常见， 影响高达80%的患者。尽管众所周知，睡眠-觉醒障碍很普遍，但情况并不好。 了解失调性睡眠-觉醒节律如何导致认知和神经精神症状 在帕金森病痴呆(PDD)和与路易体密切相关的痴呆(DLB)中。大脑的许多区域 参与调节日常睡眠-觉醒行为模式的人也是最早受到路易体影响的人 (Lb)帕金森病和德鲁巴病患者的病理学以及共同发生的阿尔茨海默病(AD)病理学。这 行政补编申请补充资金，以调查 睡眠-觉醒行为、AD共同病理以及认知和神经精神进展的紊乱模式 刘易体病的背景。我们将应用新的分析技术，如功能原理 成分分析，以新获得的连续24小时高分辨率动作图数据来评估模式 帕金森病和酒精性脂肪肝患者的睡眠觉醒行为。独特地利用伴随的PET和CSF生物标记物 来自父母赠款的tau共同病理，我们将量化纯LB患者的睡眠-觉醒行为模式 和混合的LB/AD病理。本研究的目的是：(1)确定干扰模式之间的关联 睡眠-觉醒行为与认知能力和神经精神障碍在帕金森病和德鲁巴病患者中的关系。 以及(2)帕金森病患者的睡眠-觉醒行为表型与tau共同病理的生物标志物(PET和CSF)之间的关系。 德意志银行。 建议的研究高度响应NOT-NS-21-040《协作管理补充资料》 在ADRD促进睡眠/昼夜节律研究的活动及其声明的目标是促进合作 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 中断和AD/ADRD的发病机制“。本增刊也代表了两国之间的新合作努力 睡眠研究人员(杰米·泽泽博士)和父母基金的PD/AD研究人员(波斯顿博士和 Andreasson)，并提供了一个独特的机会来研究睡眠-觉醒节奏在 与单纯LB和混合性LB/AD病理相关的认知损害和痴呆的进展 和警局和德州警局。

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.