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
• 负责人: Robert Scott Mackin
• 金额: $ 141.93万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10681480
• 关键词: Acceleration; Accounting; Address; Age; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Amygdaloid structure; Amyloid; Amyloid beta-Protein; Apolipoprotein E; Apolipoproteins; Area; Atrophic; Award; Bilateral; Cerebrovascular Circulation; Cerebrovascular Disorders; Characteristics; Chronic; Clinical; Cognition; Cognition Disorders; Cognitive; Data; Dementia; Deposition; Elderly; Evaluation; Exhibits; Genetic; Genetic Risk; Goals; Hippocampus; Impaired cognition; Individual; Inferior; Insula of Reil; Lateral; Lesion; Link; Longevity; Magnetic Resonance Imaging; Measures; Medical; Memory; Mental Depression; Nerve Degeneration; Neurobiology; Neurons; Outcome; Parents; Participant; Pathology; Positron-Emission Tomography; Recording of previous events; Risk; Risk Factors; Scanning; Selective Serotonin Reuptake Inhibitor; Severities; Speed; Symptoms; Temporal Lobe; Work; arm; cerebral atrophy; chronic depression; comorbidity; comparison group; depressive symptoms; design; entorhinal cortex; executive function; functional decline; geriatric depression; information processing; neuroimaging; research clinical testing; secondary analysis; sex; tau Proteins; white matter

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 晚期生活抑郁症（LLD）是加速的强大，最一致地确定的风险因素之一 认知能力下降和痴呆症，但促成这些关系的机制尚未 令人信服的证据表明，渐进性皮质limbic萎缩可能充当 LLD认知能力下降的主要机制。但是，一个重大的障碍是 将初期和未诊断的阿尔茨海默氏病（AD）与LLD的影响区分开来。在我们的 父母奖我们与阿尔茨海默氏病神经影像倡议（ADNI）合作开始解决 这个挑战。我们为LLD的个体创建了ADNI的兼职部门，以收集遗传， 认知和神经成像数据，包括淀粉样蛋白（Aβ）的正电子发射断层扫描（PET） 和磁共振成像（MRI）的神经变性表征AD的度量。我们的结果 已经表明：1）与未抑郁（ND）相比，LLD的认知下降是LLD的证据 在考虑Aβ，AD遗传风险（载脂蛋白ε4等位基因； APOE）和 脑血管疾病的措施（白质病变； WML），2）关键区域的神经变性 在整个生命周期中实施，包括外侧眶额皮层（OFC），上级临时 叶（STL），临时极（TP）海马（HC），杏仁核（AMG）和伏隔（AA）是 LLD的特征独立于Aβ，APOE和WML，3）LLD与焦点区域有关 脑血流异常（CBF），但相对于ND的Aβ或WML并不增加，4）基线皮质膜比 体积是与基线认知相关的强大神经生物学因素，随后 认知能力下降和抑郁症进程较差。但是，父母研究只有一个神经影像学 评估。因此，我们无法评估LLD中萎缩的进展，这对于确定 LLD认知下降的神经退行性机制。此外，我们没有获得tau宠物数据 鉴于最近的证据表明LLD与Cortico-limbic Tau沉积有关，这是至关重要的 即使没有升高的Aβ，而Tau也比Aβ在 ND。这项研究将：1）确定LLD与无关 Aβ，2）确定LLD与Cortico-limbic Tau沉积和Tau的关系的关联 LLD中的神经变性和3）确定皮质 - 纤维萎缩和tau沉积的关联 LLD的认知和9年抑郁症状。这些目标将通过进行 对父母研究的100名参与者的额外评估。我们将进行第二次神经影像 评估（MRI，PET）在初次扫描5年后，在5-- 年和7年，每六个月评估抑郁症状。来自300岁老年人的数据 ADNI-III研究匹配了人口统计学和AD风险和病理学的研究。