Slow-wave sleep enhancement in those at risk for Alzheimer's disease: Links with memory, excitotoxicity, and plasma A-beta
慢波睡眠可增强阿尔茨海默病风险人群:与记忆、兴奋性毒性和血浆 A-β 的联系
基本信息
- 批准号:10436846
- 负责人:
- 金额:$ 69.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease riskAmyloid beta-ProteinApolipoprotein EBedsBehavior TherapyBehavioralBiologicalBiological AssayCognitionCognitiveDementiaDiseaseEducationElderlyExhibitsFunctional Magnetic Resonance ImagingFunctional disorderGlutamate ReceptorGoldHealth behaviorHippocampus (Brain)HomeImpaired cognitionInterventionLinkMass Spectrum AnalysisMeasuresMediatingMemoryNerve DegenerationNeuronsNonpharmacologic TherapyPathway interactionsPharmacologyPittsburgh Compound-BPlasmaPlayPositron-Emission TomographyProcessProteinsRaceResearchRetirementRoleSleepSleep Apnea SyndromesSleeplessnessSlow-Wave SleepSynapsesTherapeutic InterventionTimeabeta accumulationabeta depositionbehavioral studycognitive changecognitive functioncognitive performancecognitive testingcostexcitotoxicityexecutive functionhuman old age (65+)improvedindexingintervention effectmemory retentionneuroimagingneuroimaging markerneurotoxicnon rapid eye movementnormal agingpre-clinicalpreservationsexsleep behaviorsleep difficultyuptake
项目摘要
Dementia caused by Alzheimer’s disease affects approximately 5.6M adults over age 65, with costs expected
to rise from $307B to $1.5T over the next 30 years. Behavioral interventions have shown promise for mitigating
neurodegeneration and cognitive impairments. Sleep is a modifiable health behavior that is critical for cognition
and deteriorates with advancing age and Alzheimer’s disease. Thus, it is a priority to examine whether
improving sleep modifies Alzheimer’s disease pathophysiology and cognitive function. Our research suggests
that deeper, more consolidated sleep is positively associated with memory and executive functions and
networks that underlie these processes. Our preliminary studies confirm that time-in-bed restriction
interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and suggest
that increases in SWA are associated with improved cognitive function. SWA reflects synaptic downscaling
predominantly among prefrontal connections. Downscaling of prefrontal connections with the hippocampus
during sleep may help to preserve the long-range connections that support memory and cognitive function. In
pre-clinical Alzheimer’s disease, hyperactivation of the hippocampus is thought to be excitotoxic and is shown
to leave neurons vulnerable to further Aβ deposition. Synaptic downscaling through SWA may mitigate the
progression of Alzheimer’s disease through these pathways. The proposed study will behaviorally increase
sleep depth (SWA) through four weeks of time-in-bed restriction in older adults characterized on Aβ deposition
and multiple factors associated with Alzheimer’s disease risk. We will examine whether behaviorally enhanced
SWA reduces hippocampal hyperactivation, leading to improved task-related prefrontal-hippocampal
connectivity, plasma Aβ levels, and cognitive function. This research addresses whether a simple, feasible,
and scalable behavioral sleep intervention improves functional neuroimaging indices of excitotoxicity,
Alzheimer’s pathophysiology, and cognitive performance.
阿尔茨海默病引起的痴呆症影响大约560万65岁以上的成年人,预计会产生费用
在未来30年内从3070亿美元增加到1.5万亿美元。行为干预已显示出减轻
神经退化和认知障碍。睡眠是一种可改变的健康行为,对认知至关重要
并随着年龄增长和老年痴呆症而恶化因此,应优先审查
改善睡眠可以改变阿尔茨海默病的病理生理学和认知功能。我们的研究表明
更深、更巩固的睡眠与记忆和执行功能呈正相关,
这些过程背后的网络。我们的初步研究证实,
干预增加睡眠效率和非快速眼动慢波活动(SWA),并建议
SWA的增加与认知功能的改善有关。SWA反映突触缩小
主要是在前额叶的连接中。前额叶与海马体的联系缩小
在睡眠期间,可能有助于保持支持记忆和认知功能的长距离连接。在
在临床前阿尔茨海默病中,海马的过度激活被认为是兴奋性毒性的,并且显示
使神经元更容易受到Aβ沉积的影响。通过SWA的突触降尺度可以减轻
阿尔茨海默病的发展通过这些途径。拟议的研究将在行为上增加
以Aβ沉积为特征的老年人通过4周卧床时间限制的睡眠深度(SWA)
以及与阿尔茨海默病风险相关的多种因素。我们将研究行为增强是否
SWA减少海马过度激活,导致任务相关的前额叶-海马
连接性、血浆Aβ水平和认知功能。本研究旨在探讨一种简单、可行、
并且可扩展的行为睡眠干预改善了兴奋性毒性的功能性神经成像指数,
阿尔茨海默病的病理生理学和认知能力。
项目成果
期刊论文数量(0)
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Kristine Ann Wilckens其他文献
Kristine Ann Wilckens的其他文献
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{{ truncateString('Kristine Ann Wilckens', 18)}}的其他基金
Slow-wave sleep enhancement in those at risk for Alzheimer's disease: Links with memory, excitotoxicity, and plasma A-beta
慢波睡眠可增强阿尔茨海默病风险人群:与记忆、兴奋性毒性和血浆 A-β 的联系
- 批准号:
10207060 - 财政年份:2021
- 资助金额:
$ 69.57万 - 项目类别:
Slow-wave sleep enhancement in those at risk for Alzheimer's disease: Links with memory, excitotoxicity, and plasma A-beta
慢波睡眠可增强阿尔茨海默病风险人群:与记忆、兴奋性毒性和血浆 A-β 的联系
- 批准号:
10602504 - 财政年份:2021
- 资助金额:
$ 69.57万 - 项目类别:
Slow-wave sleep and executive network function in older adults
老年人的慢波睡眠和执行网络功能
- 批准号:
9513692 - 财政年份:2017
- 资助金额:
$ 69.57万 - 项目类别:
Slow-wave sleep and executive network function in older adults
老年人的慢波睡眠和执行网络功能
- 批准号:
9263852 - 财政年份:2016
- 资助金额:
$ 69.57万 - 项目类别:
Slow-wave sleep and executive network function in older adults
老年人的慢波睡眠和执行网络功能
- 批准号:
9916701 - 财政年份:2016
- 资助金额:
$ 69.57万 - 项目类别:
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