Impact of sleep apnea and its treatment on memory and tau accumulation in the brain
睡眠呼吸暂停及其治疗对记忆和大脑中 tau 蛋白积累的影响
基本信息
- 批准号:10602432
- 负责人:
- 金额:$ 82.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAdherenceAffectAftercareAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease riskAlzheimer’s disease biomarkerAmyloidAmyloid beta-42AnatomyApneaArousalBloodBrainBrain StemBrain imagingCerebrospinal FluidChronicClinicalCognitiveCommunitiesConsensusDataDeteriorationDiseaseDisorientationDrowsinessEducationElderlyGenotypeHeart DiseasesHomeHourHypoxiaImpaired cognitionIndividualLong-Term EffectsLung diseasesMeasuresMedialMedicareMemoryMemory LossMetabolismMonitorNeurobehavioral ManifestationsNeurodegenerative DisordersNeurofibrillary TanglesNeuropsychological TestsObstructive Sleep ApneaOxygenPathologic ProcessesPatient Self-ReportPatientsPerformancePersonsPlasmaPolysomnographyPositron-Emission TomographyPrevalenceProcessRegulationResolutionRiskRisk FactorsRoleSenile PlaquesSeveritiesSleepSleep Apnea SyndromesSleep DisordersSleep FragmentationsSleep disturbancesSpinal PunctureSymptomsTemporal LobeTestingTimeWithdrawalactigraphyagedapolipoprotein E-4behavior measurementbrain magnetic resonance imagingcohorteffective therapyexpectationfollow-upimprovedinterestmemory processmodifiable riskneuropsychiatric disorderpositive airway pressuresexspatial memorytau Proteinstau aggregationtau-1uptakevigilanceway finding
项目摘要
Project Summary
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by the
accumulation of tau tangles and amyloid plaques. Current consensus is that the AD pathological process begins
decades before overt clinical symptoms occur. Emerging evidence suggests that sleep disruption may be an
important factor in both early cognitive deterioration leading to AD and in the metabolism of amyloid and tau.
Obstructive sleep apnea (OSA) is the most common sleep disorder in the US with an estimated prevalence of
40-50% in the cognitively normal elderly. We have previously shown that OSA severity is associated with
longitudinal increase in brain amyloid load, but less is known about the long-term effects of OSA on tau and its
hyperphosphorylation, a crucial step in the formation of tangles, as well as the effects of OSA on spatial
navigational memory, perhaps the earliest form of memory affected in AD. Our preliminary cross-sectional
data suggest that higher OSA severity is associated with higher levels of total tau (T-tau) and phosphorylated
tau (P-tau) in the cerebrospinal fluid (CSF) and poorer overnight processing of spatial navigational memory in
cognitively normal elderly. Further, self-reported presence of OSA is associated with greater longitudinal
increase in CSF T-tau and P-tau over 3 years. Although these observations implicate OSA in aberrant memory
processing and regulation of tau in the brain, a causal role for OSA in these processes would be strengthened by
additional analyses. By measuring behavioral readouts of both the encoding and processing of spatial
navigation memory, and quantifying brain tau burden with precise anatomical resolution by adding tau PET
brain imaging at baseline and 2.5 years later in 60 asymptomatic, cognitively normal older individuals with a
wide range of OSA severity who are already being followed with polysomnography (PSG), actigraphy, and
structural brain MRI as part of R01AG056031, we can test the expectations that overnight processing of spatial
memory declines longitudinally (Aim 1) and that brain tau burden increases longitudinally (Aim 2) in a way
that is dependent on measured OSA severity. A role for OSA in the metabolism of tau also would be
strengthened by treating OSA with positive airway pressure (PAP). Whereas CSF Aβ42 levels can change in a
matter of hours depending on sleep condition, CSF tau levels are thought to change over several weeks.
Therefore, we aim to examine T-tau and P-tau in CSF and T-tau in plasma prior to treatment and 8 weeks later
in 80 cognitively normal older individuals with OSA and subjective sleepiness prescribed PAP treatment for the
first time at the Mount Sinai Integrative Sleep Center (MSISC). Satisfactory PAP adherence occurs in typically
50% of patients at the MSISC, and we will monitor adherence through downloads from users' machines.
Measuring CSF and plasma tau as a function of PAP adherence serves as the basis for Aim 3.
项目摘要
阿尔茨海默病(AD)是最常见的神经退行性疾病,其特征在于:
tau缠结和淀粉样蛋白斑块的积累。目前的共识是AD病理过程开始
在临床症状出现前几十年就已经出现了新出现的证据表明,睡眠中断可能是一种
这是导致AD的早期认知恶化以及淀粉样蛋白和tau代谢的重要因素。
阻塞性睡眠呼吸暂停(OSA)是美国最常见的睡眠障碍,
40-50%的认知正常的老年人。我们之前已经表明,OSA的严重程度与
脑淀粉样蛋白负荷的纵向增加,但对OSA对tau蛋白及其代谢的长期影响知之甚少。
过度磷酸化,缠结形成的关键步骤,以及OSA对空间的影响,
导航记忆,可能是AD患者最早的记忆形式。我们初步的横断面调查
数据表明,较高的OSA严重程度与较高水平的总tau蛋白(T-tau)和磷酸化tau蛋白相关。
tau蛋白(P-tau蛋白)和空间导航记忆的夜间处理较差。
认知正常的老年人此外,自我报告的OSA的存在与更大的纵向相关。
CSF T-tau和P-tau在3年内增加。尽管这些观察结果表明阻塞性睡眠呼吸暂停综合征与异常记忆有关
大脑中tau蛋白的加工和调节,OSA在这些过程中的因果作用将通过以下方式得到加强:
更多的分析。通过测量编码和处理空间信息的行为读数,
导航记忆,并通过添加tau PET以精确的解剖分辨率定量脑tau负荷
在基线和2.5年后,60名无症状,认知正常的老年人的脑成像,
已经接受多导睡眠图(PSG)、体动图和
作为R 01 AG 056031的一部分,我们可以测试过夜空间处理的预期,
记忆力纵向下降(目标1),大脑tau蛋白负荷纵向增加(目标2),
这取决于测量的OSA严重程度。OSA在tau代谢中的作用也将是
通过用气道正压通气(PAP)治疗OSA来加强。而CSF Aβ42水平可以在一段时间内变化,
根据睡眠状况,CSF tau水平被认为在几周内发生变化。
因此,我们的目标是在治疗前和8周后检查CSF中的T-tau和P-tau以及血浆中的T-tau
在80名认知正常的OSA和主观嗜睡的老年人中,
西奈山综合睡眠中心(MSISC)令人满意的PAP依从性通常发生在
MSISC中有50%的患者,我们将通过从用户机器上下载来监控依从性。
测量CSF和血浆tau作为PAP依从性的函数作为目标3的基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Ricardo S Osorio其他文献
Ricardo S Osorio的其他文献
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{{ truncateString('Ricardo S Osorio', 18)}}的其他基金
Effects of Successful OSA TreatmENT on Memory and AD BIomarkers in Older AduLts (ESSENTIAL)
成功的 OSA 治疗对老年人记忆力和 AD 生物标志物的影响(必要)
- 批准号:
10753292 - 财政年份:2023
- 资助金额:
$ 82.13万 - 项目类别:
Impact of sleep apnea and its treatment on memory and tau accumulation in the brain
睡眠呼吸暂停及其治疗对记忆和大脑中 tau 蛋白积累的影响
- 批准号:
10380657 - 财政年份:2020
- 资助金额:
$ 82.13万 - 项目类别:
Sleep Aging and Risk for Alzheimer's disease-Resubmission-1
睡眠老化和阿尔茨海默病风险-Resubmission-1
- 批准号:
9918202 - 财政年份:2019
- 资助金额:
$ 82.13万 - 项目类别:
Sleep Aging and Risk for Alzheimer's disease-Resubmission-1
睡眠老化和阿尔茨海默病风险-Resubmission-1
- 批准号:
10343739 - 财政年份:2018
- 资助金额:
$ 82.13万 - 项目类别:
Sleep Aging and Risk for Alzheimer's disease-Resubmission-1
睡眠老化和阿尔茨海默病风险-Resubmission-1
- 批准号:
10113497 - 财政年份:2018
- 资助金额:
$ 82.13万 - 项目类别:
Brain Sleep Clearance of Amyloid-Beta Peptides Study (Brain SCRAPS)
大脑睡眠清除β-淀粉样肽研究(脑 SCRAPS)
- 批准号:
8970025 - 财政年份:2015
- 资助金额:
$ 82.13万 - 项目类别:
Sleep Disordered Breathing in normal elderly and risk for Alzheimers Disease
正常老年人的睡眠呼吸障碍与阿尔茨海默病的风险
- 批准号:
8680368 - 财政年份:2013
- 资助金额:
$ 82.13万 - 项目类别:
Sleep Disordered Breathing in normal elderly and risk for Alzheimers Disease
正常老年人的睡眠呼吸障碍与阿尔茨海默病的风险
- 批准号:
8918084 - 财政年份:2013
- 资助金额:
$ 82.13万 - 项目类别:
Sleep Disordered Breathing in normal elderly and risk for Alzheimers Disease
正常老年人的睡眠呼吸障碍与阿尔茨海默病的风险
- 批准号:
9095481 - 财政年份:2013
- 资助金额:
$ 82.13万 - 项目类别:
Sleep Disordered Breathing in normal elderly and risk for Alzheimers Disease
正常老年人的睡眠呼吸障碍与阿尔茨海默病的风险
- 批准号:
8483142 - 财政年份:2013
- 资助金额:
$ 82.13万 - 项目类别:
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