Characterizing Cognitive Decline in Late Life Depression: The ADNI-D Project
晚年抑郁症认知衰退的特征:ADNI-D 项目
基本信息
- 批准号:10522904
- 负责人:
- 金额:$ 118.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-08-01 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAddressAgeAllelesAlzheimer&aposs DiseaseAlzheimer&aposs disease riskAmygdaloid structureAmyloidAmyloid beta-ProteinApolipoproteinsAreaAtrophicAwardBilateralCerebrovascular CirculationCerebrovascular DisordersCharacteristicsChronicClinicalCognitionCognition DisordersCognitiveDataDementiaDepositionElderlyEvaluationExhibitsGeneticGenetic RiskGoalsHippocampus (Brain)Impaired cognitionIndividualInferiorInsula of ReilLateralLesionLinkLongevityMagnetic Resonance ImagingMeasuresMedicalMemoryMental DepressionNerve DegenerationNeurobiologyNeuronsOutcomeParentsParticipantPathologyPositron-Emission TomographyRecording of previous eventsRiskRisk FactorsScanningSelective Serotonin Reuptake InhibitorSeveritiesSpeedTemporal LobeWorkarmcerebral atrophychronic depressioncomorbiditycomparison groupdepressive symptomsdesignentorhinal cortexexecutive functionfunctional declinegeriatric depressioninformation processingneuroimagingresearch clinical testingsecondary analysissexsymptom treatmenttau Proteinswhite matter
项目摘要
Project Summary
Late life depression (LLD) is one of the strongest and most consistently identified risk factors for accelerated
cognitive decline and dementia but the mechanisms contributing to these relationships have not yet been
adequately clarified. Compelling evidence suggests that progressive cortico-limbic atrophy may act as a
primary mechanism of accelerated cognitive decline in LLD. However, a significant barrier has been
differentiating the effects of incipient and undiagnosed Alzheimer’s disease (AD) from those of LLD. In our
parent award we partnered with the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to begin to address
this challenge. We created an adjunct arm of ADNI for individuals with LLD in order to collect genetic,
cognitive, and neuroimaging data, including Positron Emission Tomography (PET) measures of amyloid (Aβ)
and Magnetic Resonance Imaging (MRI) measures of neurodegeneration that characterize AD. Our results
have shown that: 1) Accelerated cognitive decline is evident in LLD compared to Non-Depressed (ND) older
adults over 30 months after accounting for Aβ, AD genetic risk (Apolipoprotein ε4 alleles; APOE), and
measures of cerebrovascular disease (white matter lesions; WML), 2) Neurodegeneration in key regions
implicated in depression across the lifespan, including the lateral orbitofrontal cortex (OFC), superior temporal
lobe (STL), temporal pole (TP) hippocampus (HC), amygdala (AMG) and accumbens area (AA) were
characteristic of LLD independent of Aβ, APOE, and WML, 3) LLD was associated with focal regions of
abnormal cerebral blood flow (CBF) but not increased Aβ or WML relative to ND, and 4) Baseline cortico-limbic
volumes were the strongest neurobiological factors associated with baseline cognition and subsequent
cognitive decline and worse course of depression. However the parent study had only one neuroimaging
evaluation. As such, we could not evaluate progression of atrophy in LLD which is essential to determine
neurodegenerative mechanisms of cognitive decline in LLD. Additionally, we did not obtain tau PET data which
is critical given recent evidence that suggests LLD is associated with increased cortico-limbic tau deposition
even in absence of elevated Aβ and that tau is more strongly linked to atrophy and cognitive decline than Aβ in
ND. This study will: 1) Determine the association of LLD with progressive cortico-limbic atrophy independent of
Aβ, 2) Determine the association of LLD with increased cortico-limbic tau deposition and the relationship of tau
with neurodegeneration in LLD, and 3) Determine the association of cortico-limbic atrophy and tau deposition
with 7-year cognitive and 9-year depression outcomes in LLD. These goals will be achieved by conducting
additional evaluations of 100 participants from the parent study. We will conduct a second neuroimaging
evaluation (MRI, PET) 5 years after their initial scans, complete clinical evaluations (psychiatric, cognitive) at 5-
years and 7-years, and evaluate depression symptoms every six months. Data from 300 ND older adults from
the ADNI-III study matched for demographic and AD risk and pathology will be used for group comparisons.
项目摘要
晚年抑郁症(LLD)是加速抑郁症的最强和最一致的风险因素之一。
认知能力下降和痴呆症,但机制有助于这些关系还没有
充分澄清。令人信服的证据表明,进行性皮质边缘系统萎缩可能是一种
LLD中认知能力加速下降的主要机制。然而,一个重大障碍是,
区分早期和未确诊的阿尔茨海默病(AD)与LLD的影响。在我们
我们与阿尔茨海默病神经影像学倡议(ADNI)合作,开始解决父母奖
这个挑战。我们为LLD患者创建了ADNI的辅助臂,以收集遗传,
认知和神经影像学数据,包括淀粉样蛋白(Aβ)的正电子发射断层扫描(PET)测量
和表征AD的神经变性的磁共振成像(MRI)测量。我们的结果
研究表明:1)与非抑郁(ND)老年人相比,LLD的认知能力明显加速下降
考虑Aβ、AD遗传风险(载脂蛋白ε4等位基因; APOE)后30个月以上的成人,以及
脑血管疾病(白色病变; WML)的测量,2)关键区域的神经变性
在整个生命周期中与抑郁症有关,包括外侧眶额皮质(OFC),上级颞叶
海马(HC)、杏仁核(AMG)、颞叶(STL)、颞极(TP)和杏仁核(AA)等脑区的形态学改变。
LLD的特征独立于Aβ、APOE和WML,3)LLD与Aβ、APOE和WML的局灶性区域相关,
脑血流量(CBF)异常,但相对于ND,Aβ或WML未增加,以及4)基线皮质边缘系统
体积是与基线认知和随后的认知相关的最强神经生物学因素。
认知能力下降和抑郁症恶化。然而,母研究只有一个神经成像
评价因此,我们无法评估LLD的萎缩进展,而这对于确定
LLD中认知下降的神经退行性机制。此外,我们没有获得tau PET数据,
鉴于最近的证据表明LLD与皮质边缘tau沉积增加有关,
即使在没有Aβ升高的情况下,tau蛋白与萎缩和认知能力下降的关系也比Aβ更密切。
ND.本研究将:1)确定LLD与进行性皮质边缘萎缩的相关性,
2)确定LLD与皮质边缘tau沉积增加的相关性以及tau蛋白与LLD的关系。
与LLD中的神经退行性变,以及3)确定皮质边缘萎缩和tau沉积的关联
LLD患者7年认知和9年抑郁结局。这些目标将通过开展
对来自母研究的100名参与者进行额外评价。我们会进行第二次神经成像
首次扫描后5年进行临床评估(MRI,PET),5- 10岁时完成临床评估(精神病学,认知)。
每6个月评估一次抑郁症状。来自300名ND老年人的数据,
人口统计学和AD风险和病理学匹配的ADNI-III研究将用于组比较。
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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Robert Scott Mackin其他文献
Robert Scott Mackin的其他文献
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{{ truncateString('Robert Scott Mackin', 18)}}的其他基金
Predicting populations at-risk of developing pathological hoarding
预测有病理性囤积风险的人群
- 批准号:
10253596 - 财政年份:2020
- 资助金额:
$ 118.55万 - 项目类别:
Hoarding disorder in older adults: cognition, etiology and functional impact
老年人囤积障碍:认知、病因和功能影响
- 批准号:
10418038 - 财政年份:2018
- 资助金额:
$ 118.55万 - 项目类别:
Hoarding disorder in older adults: cognition, etiology and functional impact
老年人囤积障碍:认知、病因和功能影响
- 批准号:
9751394 - 财政年份:2018
- 资助金额:
$ 118.55万 - 项目类别:
Hoarding disorder in older adults: cognition, etiology and functional impact
老年人囤积障碍:认知、病因和功能影响
- 批准号:
10171917 - 财政年份:2018
- 资助金额:
$ 118.55万 - 项目类别:
Hoarding disorder in older adults: cognition, etiology and functional impact
老年人囤积障碍:认知、病因和功能影响
- 批准号:
10429983 - 财政年份:2018
- 资助金额:
$ 118.55万 - 项目类别:
Multimodal MRI Characteristics of Psychotherapy Response in Late Life Depression
晚年抑郁症心理治疗反应的多模态 MRI 特征
- 批准号:
9069525 - 财政年份:2015
- 资助金额:
$ 118.55万 - 项目类别:
Characterizing Cognitive Decline in Late Life Depression: The ADNI-D Project
晚年抑郁症认知衰退的特征:ADNI-D 项目
- 批准号:
8505084 - 财政年份:2013
- 资助金额:
$ 118.55万 - 项目类别:
Characterizing Cognitive Decline in Late Life Depression: The ADNI-D Project
晚年抑郁症认知衰退的特征:ADNI-D 项目
- 批准号:
8893143 - 财政年份:2013
- 资助金额:
$ 118.55万 - 项目类别:
Characterizing Cognitive Decline in Late Life Depression: The ADNI-D Project
晚年抑郁症认知衰退的特征:ADNI-D 项目
- 批准号:
9116305 - 财政年份:2013
- 资助金额:
$ 118.55万 - 项目类别:
Characterizing Cognitive Decline in Late Life Depression: The ADNI-D Project
晚年抑郁症认知衰退的特征:ADNI-D 项目
- 批准号:
10681480 - 财政年份:2013
- 资助金额:
$ 118.55万 - 项目类别:
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