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
• 负责人: Robert Scott Mackin
• 金额: $ 66.48万
• 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 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9116305
• 关键词: Accounting; Age of Onset; Alzheimer' s Disease; Amyloid deposition; Apolipoprotein E; Biological Markers; Cerebrovascular Circulation; Cerebrovascular Disorders; Characteristics; Clinical; Clinical Data; Clinical assessments; Cognitive; Comorbidity; Data; Depressed mood; Diagnostic; Disease; Disease remission; Elderly; Enrollment; Evaluation; Executive Dysfunction; Exhibits; Genetic; Genotype; Goals; Health; Health Care Costs; Impaired cognition; Investigation; Language; Lead; Magnetic Resonance Imaging; Measures; Medical; Memory; Mental Depression; Neurobiology; Neurodegenerative Disorders; Outcome; Participant; Pattern; Performance; Pharmaceutical Preparations; Recording of previous events; Relapse; Research; Scientist; Signal Transduction; Site; Techniques; Thick; Work; arm; base; brain abnormalities; cerebral atrophy; cognitive function; comparison group; cost efficient; disability; executive function; follow up assessment; follow-up; frontal lobe; geriatric depression; improved; in vivo; neuroimaging; non-demented; programs; radioligand; relating to nervous system; treatment trial; white matter

DESCRIPTION (provided by applicant): The overall goal of this program of research is to identify the neurobiological substrates of cognitive impairment (CI) in late life depression (LLD). CI represents one of the most debilitating and costly aspects of LLD and occurs in up to 60% of depressed older adults. While it is recognized that: 1) LLD is a relapsing-remitting disorder, 2) CI in some cognitive domains improves following remission of LLD (remediable CI) but the majority of CI persist, 3) LLD is a commonly co-occurring feature of several neurodegenerative diseases in older adults, and 4) LLD is associated with accelerated cognitive decline in older adults; the cause(s) of CI in LLD are not well understood. Therefore the identification of neurobiological substrates of CI represents a significant opportunity to improve health and disability outcomes for older adults with depression. Previous work has focused primarily on the association of white matter signal hyperintensities (WMSH) and CI in LLD but recent findings demonstrating prominent cortical thickness and cerebral blood flow abnormalities in LLD suggest these brain abnormalities may also be primary mechanisms contributing to CI. However, differentiating the impact of concurrent neurodegenerative disease(s) such as cerebrovascular disease and incipient Alzheimer's disease (AD) on CI in LLD has represented a significant obstacle. With the advent of new MRI techniques, including radioligands to evaluate amyloid deposition in vivo and the establishment of national research consortiums developed to identify neural substrates of CI in older adults there is now a tremendous opportunity to clarify the neurobiological substrates of CI in LLD. The specific goals of this investigation are: 1) To clarify the impact of cerebral blood flow, cortical thickness, and amyloid deposition on CI in LLD, and 2) To determine the impact of depression on course of cognitive decline in older adults. These goals will be achieved by enrolling 120 subjects with LLD into an adjunct arm of the Alzheimer's Disease Neuroimaging Initiative study (ADNI-II). ADNI-II is a five-year 69 million dollar study conducted to identify neuroimaging abnormalities and biomarkers of Alzheimer's disease and cognitive decline in older adults. For the proposed five year study, 120 LLD subjects will be enrolled at three recruitment sites and will participate in two evaluations. At baseline LLD participants will be evaluated to obtain neuroimaging and clinical data (depression, cognitive, genetic). After 2.5 years a clinical follow up assessment (cognitive, depression) will be conducted. Data from 300 non-depressed and non-demented older adults will be obtained from the ADNI-II study for between group comparisons. All data collected would be made available to scientists worldwide.

描述（由申请人提供）：该研究计划的总体目标是确定后期生活抑郁症（LLD）中认知障碍（CI）的神经生物学基质。 CI是LLD中最衰弱和昂贵的方面之一，最多发生在抑郁症的老年人中。虽然人们认识到：1）LLD是一种复发障碍，但在某些认知领域的CI中，CI在LLD缓解后改善（可补救的CI），但大多数CI持续存在，3）LLD通常是一种与老年人的几种神经变性疾病相关的特征，以及4）LLD与老年人相关的疾病，与老年人相关。 LLD中CI的原因尚不清楚。因此，CI的神经生物学底物的鉴定是改善抑郁症老年人健康和残疾结果的重要机会。先前的工作主要集中在LLD中白质信号高强度（WMSH）和CI的关联，但最近的发现表明LLD中明显的皮质厚度和脑血流异常表明这些脑异常也可能是对CI有助于CI的主要机制。然而，区分并发神经退行性疾病的影响，例如脑血管疾病和初期的阿尔茨海默氏病（AD）对LLD中CI的影响已经是一个重要的障碍。随着新的MRI技术的出现，包括评估体内淀粉样蛋白沉积的放射性配体，并建立了国家研究联盟，以识别老年人中CI的神经底物，现在有一个巨大的机会来阐明LLD中CI的神经生物学基质。这项研究的具体目标是：1）阐明脑血流，皮质厚度和淀粉样蛋白沉积对LLD中CI的影响， 2）确定抑郁症对老年人认知能力下降的影响。这些目标将通过将120名具有LLD的受试者纳入阿尔茨海默氏病神经影像学倡议研究（ADNI-II）的辅助部门来实现。 ADNI-II是一项为期五年的6900万美元研究，旨在鉴定阿尔茨海默氏病的异常和生物标志物以及老年人的认知下降。对于拟议的五年研究，将在三个招聘场所招募120名LLD受试者，并将参加两次评估。将在基线上评估LLD参与者以获得神经影像学和临床数据（抑郁，认知，遗传）。经过2。5年后，将进行临床随访评估（认知，抑郁症）。来自ADNI-II研究将获得来自300名未抑郁和未痴呆的老年人的数据，以在小组比较之间进行。收集的所有数据将提供给全球科学家。