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
• 负责人: Robert Scott Mackin
• 金额: $ 65.76万
• 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 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8893143
• 关键词: Accounting; Age of Onset; Alzheimer' s Disease; Amyloid deposition; Apolipoprotein E; Biological Markers; Brain; 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; Relative (related person); Research; Scientist; Signal Transduction; Site; Techniques; Thick; Work; arm; base; cerebral atrophy; cognitive function; comparison group; cost efficient; disability; executive function; follow up assessment; follow-up; frontal lobe; geriatric depression; improved; in vivo; neuroimaging; 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晚年抑郁症（LLD）中认知障碍（CI）的神经生物学基础。 CI 是 LLD 中最令人衰弱且代价最高的方面之一，高达 60% 的抑郁老年人会发生 CI。虽然人们认识到：1) LLD 是一种复发缓解型疾病，2) LLD 缓解后某些认知领域的 CI 有所改善（可治愈 CI），但大多数 CI 持续存在，3) LLD 是老年人中几种神经退行性疾病的常见共同特征，4) LLD 与老年人加速认知衰退有关； LLD 中 CI 的原因尚不清楚。因此，识别 CI 的神经生物学底物为改善患有抑郁症的老年人的健康和残疾结果提供了重要机会。之前的工作主要集中在 LLD 中白质信号高信号 (WMSH) 与 CI 的关联，但最近的研究结果表明 LLD 中显着的皮质厚度和脑血流异常表明这些大脑异常也可能是导致 CI​​ 的主要机制。然而，区分并发神经退行性疾病（例如脑血管疾病和早期阿尔茨海默氏病 (AD)）对 LLD 中 CI 的影响是一个重大障碍。随着新 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，以及为识别老年人 CI 神经底物而开发的国家研究联盟的建立，现在有一个巨大的机会来阐明 LLD 中 CI 的神经生物学底物。本研究的具体目标是：1）阐明脑血流量、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过程的影响。这些目标将通过将 120 名 LLD 受试者纳入阿尔茨海默病神经影像倡议研究 (ADNI-II) 的辅助组来实现。 ADNI-II 是一项为期五年、耗资 6900 万美元的研究，旨在识别老年人的神经影像异常以及阿尔茨海默病和认知能力下降的生物标志物。对于拟议的五年研究，将在三个招募地点招募 120 名法学博士受试者，并参加两项评估。在基线时，LLD 参与者将接受评估以获得神经影像和临床数据（抑郁、认知、遗传）。 2.5 年后将进行临床随访评估（认知、抑郁）。 ADNI-II 研究将从 300 名非抑郁症和非痴呆老年人的数据中获取数据，以进行组间比较。收集到的所有数据将提供给全世界的科学家。