Sleep and Temperature Disturbance as risk factors for Alzheimer's Disease in Down Syndrome: a Longitudinal Study
睡眠和体温紊乱是唐氏综合症中阿尔茨海默病的危险因素:一项纵向研究
基本信息
- 批准号:10591135
- 负责人:
- 金额:$ 187.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-02-01 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAdultAffectAgeAge of OnsetAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease riskAlzheimer’s disease biomarkerAmyloidAmyloid beta-42Amyloid beta-ProteinApneaBiological MarkersBloodBody TemperatureBrainBrain regionCause of DeathCerebrospinal FluidCircadian DysregulationCircadian RhythmsClinicalCognitionCognitiveCollectionDataData CollectionDementiaDisease MarkerDisease ProgressionDown SyndromeEarly Onset Alzheimer DiseaseElderlyEvaluationFunctional disorderGeneticGenetic DiseasesGoalsHeterogeneityHigh PrevalenceHippocampusHomeHourImpaired cognitionIndividualIntellectual functioning disabilityInterventionLeadLifeLife ExpectancyLightLiteratureLongitudinal StudiesLongitudinal, observational studyMagnetic Resonance ImagingMeasurementMeasuresMedicalModelingNerve DegenerationObstructive Sleep ApneaOnset of illnessOutcomePathologyPersonsPhysiologic ThermoregulationPlasmaPolysomnographyPopulationPositron-Emission TomographyResearchRisk FactorsSeveritiesSleepSleep disturbancesSlow-Wave SleepStructureStudy modelsTelemetryTemperatureTestingThickWorkWristactigraphyage relatedagedapolipoprotein E-4autosomal dominant Alzheimer&aposs diseasecircadiancognitive changecognitive performancecognitive testingcohortfollow-uphigh riskindexinglifetime riskmodifiable riskneurofilamentneuroimagingnovelpre-clinicalprogression markerrate of changerecruitscreeningsexsymptomatologytau Proteinstau-1uptake
项目摘要
Project Summary Abstract
Down syndrome (DS), the most frequent form of intellectual disability of genetic origin, involves a >95%
cumulative risk of Alzheimer’s Disease (AD) by the seventh decade. Further, AD is now the most common cause
of death in this population as life expectancy in DS individuals has increased. Importantly, while AD in DS
individuals has a mean age of onset 20–30 years younger compared to euploid individuals, there is substantial
heterogeneity in this age of onset (between 40 and 70 years old), emphasizing the urgent need to identify and
treat modifiable causes of AD in DS. Our work in the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI)
Cohort has established that clinical and Amyloid/Tau/Neurodegeneration (ATN) related biomarker changes in
DS have a similar temporal profile to that in sporadic and autosomal dominant AD, meaning these biomarkers
may be used to identify modifiable causes of AD in DS individuals prior to AD dementia onset. Existing literature
and our preliminary data suggest that potential causes of AD in euploid individuals, namely age-related sleep
and body temperature (Tb) circadian rhythm disturbance, are more severely perturbed in DS compared to
euploid older adults: specifically, results suggest that greater obstructive sleep apnea (OSA) severity and lower
Tb are particularly important modifiable AD risk factors in DS. This project will test the hypotheses that greater
baseline OSA severity and lower baseline Tb will longitudinally predict ATN AD biomarker increase and cognitive
decline in initially cognitively stable DS adults. We will recruit 60 DS adults with normal cognition aged 40–60
years old and follow them longitudinally at three annual timepoints over 2 years. Baseline assessments will
include screening; cognitive evaluation; at home and in lab polysomnographic assessments overlapping with 36
hours of telemetrically measured Tb data collection, and collection of ATN biomarkers including amyloid
(flutemetamol PET SUVR, plasma Aβ), tau (PI-2620 PET SUVR, plasma T-tau and P-tau181) and
neurodegeneration (hippocampal volume, cortical thickness, plasma neurofilament light) related biomarkers.
Follow-up cognitive evaluations and collection of plasma-based biomarkers will occur annually at all three
timepoints, and neuroimaging-based biomarkers at two timepoints (baseline and 2 years). The goals of this study
are to test 1) Whether greater baseline OSA apnea hypopnea index (AHI3A) is associated with ATN biomarker
severity (Aim 1), 2) Whether lower baseline Tb is associated with greater tau biomarker severity (Aim 2), and 3)
Whether OSA severity and lower Tb longitudinally predict greater estimated rate of change in AD biomarkers
(Aim 3). Predictors of cognitive decline and additional sleep and Tb parameters will be explored. This novel
proposal will advance our understanding of how age-related sleep and thermoregulatory disturbances impact
AD biomarker progression in people with DS—a population at high risk for all three AD, OSA, and temperature
dysregulation—with the aim of identifying modifiable risk factors in both DS and euploid individuals.
项目概要 摘要
唐氏综合症 (DS) 是最常见的遗传性智力障碍,涉及 >95%
到七十岁时,阿尔茨海默病(AD)的累积风险。此外,AD 现在是最常见的原因
随着 DS 个体预期寿命的增加,该人群的死亡人数增加。重要的是,虽然 DS 中的 AD
与整倍体个体相比,个体的平均发病年龄年轻 20-30 岁,
该发病年龄(40 至 70 岁)的异质性,强调迫切需要识别和
治疗 DS 中 AD 的可改变原因。我们在唐氏阿尔茨海默症巴塞罗那神经影像计划 (DABNI) 中的工作
队列已确定临床和淀粉样蛋白/Tau/神经退行性变 (ATN) 相关的生物标志物变化
DS 与散发性和常染色体显性 AD 具有相似的时间特征,这意味着这些生物标志物
可用于在 AD 痴呆发作之前识别 DS 个体中 AD 的可改变原因。现有文献
我们的初步数据表明,整倍体个体中 AD 的潜在原因,即与年龄相关的睡眠
与 DS 相比,体温 (Tb) 昼夜节律紊乱更严重
整倍体老年人:具体而言,结果表明阻塞性睡眠呼吸暂停 (OSA) 的严重程度更高,且
Tb 是 DS 中特别重要的可改变的 AD 危险因素。该项目将测试更大的假设
基线 OSA 严重程度和较低基线 Tb 将纵向预测 ATN AD 生物标志物增加和认知能力
最初认知稳定的 DS 成年人的下降。我们将招募60名40-60岁认知正常的DS成年人
岁,并在两年内的三个年度时间点纵向跟踪它们。基线评估将
包括筛查;认知评估;在家和实验室多导睡眠图评估重叠 36
数小时的遥测测量 Tb 数据收集以及 ATN 生物标志物(包括淀粉样蛋白)的收集
(氟替他莫 PET SUVR、血浆 Aβ)、tau(PI-2620 PET SUVR、血浆 T-tau 和 P-tau181)和
神经退行性变(海马体积、皮质厚度、血浆神经丝光)相关的生物标志物。
所有三个中心每年都会进行后续认知评估和血浆生物标志物收集
时间点,以及两个时间点(基线和 2 年)的基于神经影像的生物标志物。本研究的目标
要测试 1) 较高的基线 OSA 呼吸暂停低通气指数 (AHI3A) 是否与 ATN 生物标志物相关
严重程度(目标 1)、2) 较低的基线 Tb 是否与较高的 tau 生物标志物严重程度相关(目标 2)和 3)
OSA 严重程度和较低 Tb 是否纵向预测 AD 生物标志物的估计变化率更大
(目标 3)。将探讨认知能力下降的预测因素以及额外的睡眠和结核病参数。这部小说
该提案将增进我们对与年龄相关的睡眠和体温调节障碍如何影响的理解
DS 患者的 AD 生物标志物进展——AD、OSA 和体温这三种疾病的高危人群
失调——目的是识别 DS 和整倍体个体中可改变的危险因素。
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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Esther Marian Blessing其他文献
Esther Marian Blessing的其他文献
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{{ truncateString('Esther Marian Blessing', 18)}}的其他基金
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- 批准号:
10706609 - 财政年份:2022
- 资助金额:
$ 187.12万 - 项目类别:
Investigating the Temperature Dependence of Age-related Tau Pathology Relevant to Early Alzheimer's Disease
研究与早期阿尔茨海默病相关的年龄相关 Tau 病理学的温度依赖性
- 批准号:
10612943 - 财政年份:2021
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$ 187.12万 - 项目类别:
Investigating the Temperature Dependence of Age-related Tau Pathology Relevant to Early Alzheimer's Disease
研究与早期阿尔茨海默病相关的年龄相关 Tau 病理学的温度依赖性
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10302079 - 财政年份:2021
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$ 187.12万 - 项目类别:
Investigating the Temperature Dependence of Age-related Tau Pathology Relevant to Early Alzheimer's Disease
研究与早期阿尔茨海默病相关的年龄相关 Tau 病理学的温度依赖性
- 批准号:
10460555 - 财政年份:2021
- 资助金额:
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