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

描述(由申请者提供)：本研究计划的总体目标是确定晚年抑郁症(LLD)认知障碍(CI)的神经生物学基础。 CI代表了LLD最虚弱和最昂贵的方面之一，在高达60%的抑郁症老年人中发生。虽然人们认识到：1)LLD是一种复发-缓解性疾病，2)LLD(可补救的CI)缓解后，某些认知领域的CI有所改善，但大多数CI仍然存在，3)LLD是几种神经退行性疾病在老年人中常见的共生特征，4)LLD与老年人认知功能减退有关；LLD中CI的原因(S)尚不清楚。因此，识别CI的神经生物学底物是改善患有抑郁症的老年人的健康和残疾结果的重要机会。以往的研究主要集中在LLD患者脑白质信号高信号(WMSH)与CI之间的关系，但最近发现LLD患者存在明显的皮质厚度和脑血流异常，提示这些脑异常也可能是CI的主要机制。然而，区分并发的神经退行性疾病(S)，如脑血管疾病和早期阿尔茨海默病(AD)对LLD中CI的影响是一个显著的障碍。随着新的MRI技术的出现，包括用于评估体内淀粉样蛋白沉积的放射性配体的出现，以及为识别老年人CI的神经底物而开发的国家研究联合体的建立，现在为阐明LLD中CI的神经生物学底物提供了巨大的机会。本研究的具体目的是：1)明确脑血流、皮质厚度和淀粉样蛋白沉积对LLD CI的影响。 2)研究抑郁症对老年人认知功能减退的影响。这些目标将通过招募120名患有LLD的受试者加入阿尔茨海默病神经成像倡议研究(ADNI-II)的辅助分支来实现。ADNI-II是一项为期五年、耗资6900万美元的研究，旨在确定阿尔茨海默病和老年人认知能力下降的神经成像异常和生物标记物。在拟议的五年研究中，将在三个招聘地点招收120名学习能力较差的科目，并参加两次评估。在基线时，将对LLD参与者进行评估，以获得神经成像和临床数据(抑郁、认知、遗传)。2.5年后，将进行临床随访评估(认知、抑郁)。来自300名非抑郁症和非痴呆症老年人的数据将从ADNI-II研究中获得，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.