Pathways Linking Late-Life Depression to MCI & Dementia

描述（由研究者提供）：本R01修订申请的目的是探讨晚年抑郁（LLD）、认知功能障碍和进行性神经变性之间的关系。指导假设是LLD患者由于不同的潜在神经病理改变而发生认知障碍，这种改变通常表现为轻度认知障碍（MCI）。这些神经病理和认知变化是风险调节剂，降低大脑储备能力，进而增加患阿尔茨海默病（AD）的风险。为了实现这一目标，我们将招募LLD、MCI和正常对照受试者，以丰富我们现有的队列（通过Butters博士现有的K01奖（MH01684）“晚年抑郁症的认知功能过程”收集），共包括150名老年人、非痴呆、非抑郁受试者、60名非抑郁MCI受试者和270名LLD受试者。利用匹兹堡大学晚年情绪障碍干预研究中心（MH52247）和阿尔茨海默病研究中心（AG05133）的联合基础设施，我们将完成详细的神经行为研究！评估，包括临床，神经心理学，神经影像学和生物学标记，使用这些数据来评估与轻度认知障碍或痴呆发展相关的因素。研究对象将在至少三年的时间里每年进行一次研究，这使我们能够利用纵向数据来评估一系列相互关联的假设，这些假设假设了老年抑郁症患者产生认知障碍的途径，并可能导致一些人患上痴呆症。

DESCRIPTION (provided by investigator): The goal of this revised R01 application is to investigate the relationships among late-life depression (LLD), cognitive impairment and progressive neurodegeneration. The guiding hypothesis is that LLD patients have evolving cognitive impairments as a consequence of distinct underlying neuropathological changes, which frequently are expressed as Mild Cognitive Impairment (MCI). These neuropathological and cognitive changes are risk modifiers, lowering brain reserve capacity, and in turn, increasing risk of developing Alzheimer's Disease (AD). In order to pursue this goal we will enroll LLD, MCI, and normal control subjects to enrich our existing cohort (gathered through Dr. Butters' existing K01 Award (MH01684), "The Course of Cognitive Functioning in Late-Life depression" to include a total of 150 elderly, non-demented, non-depressed subjects, 60 nondepressed MCI subjects and 270 LLD subjects. Using the joint infrastructure of the University of Pittsburgh's Intervention Research Center for Late-Life Mood Disorders (MH52247) and the Alzheimer's Disease Research Center (AG05133) we will complete a detailed neurobehaviora! evaluation, including clinical, neuropsychological, neuroimaging and biological markers, using these data to evaluate the factors associated with the development of MCI or dementia. Subjects will be studied annually for at least three years, allowing us to use longitudinal data to evaluate a series of linked hypotheses that postulate the pathways by which elderly, depressed patients develop cognitive impairment, and which may lead some to develop dementia.