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

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.
项目概要 晚年抑郁症(LLD)是加速抑郁症最强烈、最一致的危险因素之一。 认知能力下降和痴呆,但导致这些关系的机制尚未被阐明 充分澄清。令人信服的证据表明进行性皮质边缘萎缩可能是一种 LLD 认知加速衰退的主要机制。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。在我们的 我们与阿尔茨海默病神经影像计划 (ADNI) 合作,开始解决家长奖 这个挑战。我们为 LLD 患者创建了 ADNI 的附属机构,以收集遗传、 认知和神经影像数据,包括淀粉样蛋白 (Aβ) 的正电子发射断层扫描 (PET) 测量 磁共振成像 (MRI) 测量 AD 特征的神经退行性变。我们的成果 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)和 AD 遗传风险后 30 个月以上的成年人 脑血管疾病(白质病变;WML)的测量,2)关键区域的神经退行性变 与整个生命周期的抑郁症有关,包括外侧眶额皮质(OFC)、颞上皮质 脑叶(STL)、颞极(TP)、海马(HC)、杏仁核(AMG)和伏隔核区(AA) LLD 的特征与 Aβ、APOE 和 WML 无关,3) LLD 与局部区域相关 与 ND 相比,脑血流量 (CBF) 异常,但 Aβ 或 WML 未增加,4) 基线皮质边缘 容量是与基线认知和后续认知相关的最强的神经生物学因素 认知能力下降和抑郁症恶化。然而,母研究只有一项神经影像学检查 评估。因此,我们无法评估 LLD 萎缩的进展情况,而这对于确定 LLD 认知能力下降的神经退行性机制。此外,我们没有获得 tau PET 数据,这 鉴于最近的证据表明 LLD 与皮质边缘 tau 沉积增加有关,这一点至关重要 即使在 Aβ 水平不升高的情况下,tau 蛋白与萎缩和认知能力下降的相关性也比 Aβ 更强 ND。这项研究将: 1) 确定 LLD 与进行性皮质边缘萎缩的关联,独立于 Aβ, 2) 确定 LLD 与皮质边缘 tau 沉积增加的关联以及 tau 的关系 LLD 中的神经退行性疾病,以及 3) 确定皮质边缘萎缩和 tau 沉积的关联 LLD 中 7 年认知结果和 9 年抑郁结果。这些目标将通过开展 对母研究中 100 名参与者的额外评估。我们将进行第二次神经影像检查 首次扫描后 5 年进行评估(MRI、PET),5 岁时完成临床评估(精神、认知) 岁和七岁,每六个月评估一次抑郁症状。数据来自 300 名 ND 老年人 与人口统计学、AD 风险和病理学相匹配的 ADNI-III 研究将用于组间比较。

项目成果

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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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