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.
项目摘要
唐氏综合征(DS)是最常见的遗传性智力残疾形式,涉及95%以上的
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,该人群的死亡率也在下降。重要的是,虽然AD在DS中
个体的平均发病年龄比整倍体个体小20-30岁,
发病年龄(40至70岁)的异质性,强调迫切需要确定和
在DS中治疗AD的可改变原因。巴塞罗那阿尔茨海默病神经影像学倡议(DABNI)
队列研究已经确定,临床和淀粉样蛋白/Tau/神经变性(ATN)相关的生物标志物的变化,
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的可改变的原因。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,
和体温(Tb)昼夜节律紊乱,在DS中受到的干扰比在DS中更严重。
整倍体老年人:具体来说,研究结果表明,阻塞性睡眠呼吸暂停(OSA)的严重程度越高,
结核是DS中特别重要的可改变的AD危险因素。这个项目将测试假设,
基线OSA严重程度和较低的基线Tb将纵向预测ATN AD生物标志物的增加和认知功能的改善。
最初认知稳定的DS成人的下降。我们将招募60名40-60岁认知正常的DS成年人
岁,并在2年内的三个年度时间点纵向跟踪他们。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,
小时的遥测Tb数据收集,以及ATN生物标志物的收集,包括淀粉样蛋白
(flutemetetaline PET SUVR,血浆Aβ)、tau(PI-2620 PET SUVR,血浆T-tau和P-tau 181)和
神经变性(海马体积、皮质厚度、血浆神经丝光)相关生物标志物。
在所有三个研究中心,每年都会进行随访认知评估和收集基于血浆的生物标志物。
时间点,以及两个时间点(基线和2年)的基于神经成像的生物标志物。本研究的目标
测试1)更大的基线OSA呼吸暂停低通气指数(AHI 3A)是否与ATN生物标志物相关
2)较低的基线Tb是否与较大的tau生物标志物严重性相关(Aim 2),和3)
OSA严重程度和较低的Tb是否纵向预测AD生物标志物的估计变化率更大
(Aim 3)。将探讨认知下降和额外睡眠和Tb参数的预测因素。这本小说
这项提案将促进我们对年龄相关的睡眠和体温调节紊乱如何影响
DS患者的AD生物标志物进展-所有三种AD、OSA和体温的高风险人群
失调-目的是确定DS和整倍体个体中可改变的风险因素。
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
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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
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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:
$ 187.12万 - 项目类别:
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