Characterizing Cognitive Decline in Late Life Depression: The ADNI-D Project

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最令人衰弱和代价最高的方面之一，发生在高达60%的抑郁老年人中。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并发症，4）LLD与老年人的加速认知衰退相关; LLD中CI的原因尚不清楚。因此，CI的神经生物学底物的识别是改善老年抑郁症患者健康和残疾结局的重要机会。以前的工作主要集中在协会的白色物质信号高强度（WMSH）和CI在LLD，但最近的研究结果表明，突出的皮质厚度和脑血流异常LLD表明，这些大脑异常也可能是主要的机制，有助于CI。然而，区分并发的神经退行性疾病如脑血管疾病和早期阿尔茨海默病（AD）对LLD中CI的影响是一个重大障碍。随着新的MRI技术的出现，包括放射性配体，以评估体内淀粉样蛋白沉积和建立国家研究财团开发，以确定在老年人CI的神经基板，现在有一个巨大的机会，以澄清在LLD CI的神经生物学基板。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功能下降的影响。这些目标将通过招募120名LLD受试者进入阿尔茨海默病神经影像学倡议研究（ADNI-II）的辅助研究来实现。ADNI-II是一项为期五年、耗资6900万美元的研究，旨在确定老年人阿尔茨海默病和认知能力下降的神经成像异常和生物标志物。对于拟定的5年研究，120例LLD受试者将在3个招募中心入组，并将参加2次评价。在基线时，将对LLD受试者进行评价，以获得神经影像学和临床数据（抑郁、认知、遗传）。2.5年后，将进行临床随访评估（认知、抑郁）。将从ADNI-II研究中获得300名非抑郁和非痴呆老年人的数据，用于组间比较。收集到的所有数据都将提供给世界各地的科学家。

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.